Sample records for acute alcohol withdrawal

  1. Increased QT interval variability index in acute alcohol withdrawal.

    PubMed

    Bär, Karl-Jürgen; Boettger, Michael Karl; Koschke, Mandy; Boettger, Silke; Grotelüschen, Marei; Voss, Andreas; Yeragani, Vikram K

    2007-07-10

    Acute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal. High resolution electrocardiographic recordings were performed in 18 male unmedicated patients suffering from acute alcohol withdrawal, 18 matched controls and 15 abstained alcoholics. From these, parameters of beat-to-beat heart rate and QT variability such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the severity of withdrawal symptoms and with serum electrolyte concentrations. Heart rate and QTvi were significantly increased in acute alcohol withdrawal. Abstained alcoholics did not significantly differ from controls. While QTvi correlated with the severity of alcohol withdrawal symptoms, the mean QT interval duration showed an inverse relationship with serum potassium concentrations. Our data indicate increased QT variability and thus increased repolarization lability in acute alcohol withdrawal. This might add to the elevated risk for serious cardiac arrhythmias. In part, these changes might be related to increased cardiac sympathetic activity or low potassium, thus suggesting the latter as possible targets for adjuvant pharmacological therapy during withdrawal.

  2. Preparing Nursing and Social Work Students to Care for Patients in Acute Alcohol Withdrawal.

    PubMed

    Gates, Sharon A; Brown, James R

    Alcohol and other drug abuse has become a national crisis with approximately 26% of general medical patients having alcohol-related problems. New nurses and social workers are often not prepared to care for patients with severe alcohol withdrawal symptoms because they lack experience in actual crisis situations. The purpose of this study was to prepare nursing and social work students to care for a patient undergoing an acute alcohol withdrawal process. Nine groups of 8-10 students participated in a 2.5-hour simulation event that included an alcohol withdrawal seizure, team meeting, and discharge of the patient. Students recognized the importance of all the professional roles and how each professional benefits patient care. Before the simulation, students thought they were prepared to care for patients experiencing alcohol withdrawal; however, the crisis of an alcohol seizure decreased the student's ability to perform skills and communicate effectively. These findings suggest that new nurses and social workers may not be prepared to care for the acute alcohol withdrawal patient.

  3. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study.

    PubMed

    Rosenson, Jonathan; Clements, Carter; Simon, Barry; Vieaux, Jules; Graffman, Sarah; Vahidnia, Farnaz; Cisse, Bitou; Lam, Joseph; Alter, Harrison

    2013-03-01

    Acute alcohol withdrawal syndrome (AAWS) is encountered in patients presenting acutely to the Emergency Department (ED) and often requires pharmacologic management. We investigated whether a single dose of intravenous (i.v.) phenobarbital combined with a standardized lorazepam-based alcohol withdrawal protocol decreases intensive care unit (ICU) admission in ED patients with acute alcohol withdrawal. This was a prospective, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either a single dose of i.v. phenobarbital (10 mg/kg in 100 mL normal saline) or placebo (100 mL normal saline). All patients were placed on the institutional symptom-guided lorazepam-based alcohol withdrawal protocol. The primary outcome was initial level of hospital admission (ICU vs. telemetry vs. floor ward). There were 198 patients enrolled in the study, and 102 met inclusion criteria for analysis. Fifty-one patients received phenobarbital and 51 received placebo. Baseline characteristics and severity were similar in both groups. Patients that received phenobarbital had fewer ICU admissions (8% vs. 25%, 95% confidence interval 4-32). There were no differences in adverse events. A single dose of i.v. phenobarbital combined with a symptom-guided lorazepam-based alcohol withdrawal protocol resulted in decreased ICU admission and did not cause increased adverse outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Acute withdrawal, protracted abstinence and negative affect in alcoholism: Are they linked?

    PubMed Central

    Heilig, M.; Egli, M.; Crabbe, J.C.; Becker, H.C.

    2012-01-01

    The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable? PMID:20148778

  5. Activation of brain NOP receptors attenuates acute and protracted alcohol withdrawal symptoms in the rat.

    PubMed

    Economidou, Daina; Cippitelli, Andrea; Stopponi, Serena; Braconi, Simone; Clementi, Stefano; Ubaldi, Massimo; Martin-Fardon, Rèmi; Weiss, Friedbert; Massi, Maurizio; Ciccocioppo, Roberto

    2011-04-01

    Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. In previous studies, we demonstrated that treatment with Nociceptin/orphanin FQ (N/OFQ) significantly reduces alcohol consumption and attenuates alcohol-seeking behavior induced by environmental conditioning factors or by stress in rats. In this study, we evaluated whether activation of brain NOP receptors may also attenuate alcohol withdrawal signs in rats. For this purpose, animals were subjected to a 6-day chronic alcohol intoxication (by intragastric administration), and at 8, 10, and 12 hours following cessation of alcohol exposure, they were treated intracerebroventricularly (ICV) with N/OFQ (0.0, 1.0, and 3.0 μg/rat). Somatic withdrawal signs were scored after ICV treatment. In a subsequent experiment, to evaluate N/OFQ effects on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM). In the last experiment, an additional group of rats was tested for anxiety elicited by acute ethanol intoxication (hangover anxiety). For this purpose, animals received an acute dose (3.0 g/kg) of 20% alcohol and 12 hour later were tested in the EPM following ICV N/OFQ (0.0, 1.0, and 2.0 μg/rat). Results showed that N/OFQ significantly reduced the expression of somatic withdrawal signs and reversed anxiety-like behaviors associated with both chronic and acute alcohol intoxication. N/OFQ did not affect anxiety scores in nondependent animals. These findings suggest that the N/OFQ-NOP receptor system may represent a promising target for the development of new treatments to ameliorate alcohol withdrawal symptoms. Copyright © 2011 by the Research Society on Alcoholism.

  6. Improving alcohol withdrawal outcomes in acute care.

    PubMed

    Melson, Jo; Kane, Michelle; Mooney, Ruth; Mcwilliams, James; Horton, Terry

    2014-01-01

    Excessive alcohol consumption is the nation's third leading cause of preventable deaths. If untreated, 6% of alcohol-dependent patients experience alcohol withdrawal, with up to 10% of those experiencing delirium tremens (DT), when they stop drinking. Without routine screening, patients often experience DT without warning. Reduce the incidence of alcohol withdrawal advancing to DT, restraint use, and transfers to the intensive care unit (ICU) in patients with DT. In October 2009, the alcohol withdrawal team instituted a care management guideline used by all disciplines, which included tools for screening, assessment, and symptom management. Data were obtained from existing datasets for three quarters before and four quarters after implementation. Follow-up data were analyzed and showed a great deal of variability in transfers to the ICU and restraint use. Percentage of patients who developed DT showed a downward trend. Incidence of alcohol withdrawal advancing to DT and, in patients with DT, restraint use and transfers to the ICU. Initial data revealed a decrease in percentage of patients with alcohol withdrawal who experienced DT (16.4%-12.9%). In patients with DT, restraint use decreased (60.4%-44.4%) and transfers to the ICU decreased (21.6%-15%). Follow-up data indicated a continued downward trend in patients with DT. Changes were not statistically significant. Restraint use and ICU transfers maintained postimplementation levels initially but returned to preimplementation levels by third quarter 2012. Early identification of patients for potential alcohol withdrawal followed by a standardized treatment protocol using symptom-triggered dosing improved alcohol withdrawal management and outcomes.

  7. Assessment and management of alcohol dependence and withdrawal in the acute hospital: concise guidance.

    PubMed

    Stewart, Stephen; Swain, Sharon

    2012-06-01

    Alcohol dependence is common among patients attending acute hospitals. It can be the major reason for attendance or a significant cofactor. Assessment of these patients in the acute setting can be challenging owing to the multidisciplinary approach required. Doctors in acute hospitals are often inexperienced in managing dependence, a mental health problem. They might focus on the physical harms or the withdrawal, a consequence of the dependence. For this reason, assessment of dependence and prevention and management of acute alcohol withdrawal are often suboptimal. There is little existing guidance on how to manage this patient population, especially in non-specialist settings. With recently published National Institute for Health and Clinical Excellence (NICE) guidance on the management of dependence and withdrawal, now is the perfect time to produce concise guidelines in the hope that a more succinct suite of guidance can reach a larger audience.

  8. [Evaluation of selected socioeconomic factors in patients with acute ethanol intoxication and alcohol withdrawal syndrome].

    PubMed

    Lukasik-Głębocka, Magdalena; Sommerfeld, Karina

    2014-01-01

    Ethanol is commonly overused psychoactive substance in Poland and all around the world. It causes addiction, which occurs as a result of its chronic administration. One of the main symptoms of addiction is hunger due to psychoactive substance that prevents interruption of its adoption and contributes to relapse drinking. Acute poisoning with ethyl alcohol and alcohol withdrawal syndrome are diseases causing a potential danger to life. The prevalence of use and abuse of alcoholic beverages is a potential risk, causing health problems, including permanent damage of the central and peripheral nervous system and socio-economic problems. The aim of this study is to analyze certain aspects of the socio-economic situation of the patients hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome in 2010. 299 patients history was evaluated, among which 161 were treated for acute intoxication with ethanol and 138 due to alcohol withdrawal syndrome. Objects of interest were elements of subjective tests including: marital status of patients, their education and professional activity and the problem of homelessness. The study group consisted of 299 patients in age from 16 to 77 years, hospitalized in the Department of Toxicology in Raszeja City Hospital in Poznan due to acute ethanol intoxication or alcohol withdrawal syndrome. It was found that the largest group consisted of patients remaining married (42.81%) and unmarried (30.43%). Alcohol abuse affects people of all levels of education. In the present study, most patients had a vocational education (37.79%) and medium (23.08%). Patients were analyzed in terms of economic activity, among which about 40% were unemployed. In the whole group more than 10% of those were homeless. Ethyl alcohol intoxication and alcohol withdrawal represents a significant hazard. As a result of reliance, patients lose control of alcohol consumption and they

  9. The role of salsolinol in alcohol intake and withdrawal.

    PubMed

    Clow, A; Topham, A; Saunders, J B; Murray, R; Sandler, M

    1985-01-01

    We studied the urinary excretion of the tetrahydroisoquinoline (TIQ) salsolinol, formed from acetaldehyde and dopamine, in both severely and moderately dependent alcoholics during withdrawal from alcohol and subsequent challenge with an acute dose of alcohol and L-dopa, and compared these results with controls. Plasma acetaldehyde and alcohol levels in a sub-population of severely dependent withdrawn alcoholic and control subjects following an acute dose of alcohol were also determined. Salsolinol excretion during the first 4 days of alcohol withdrawal was variable but 10 out of 14 alcoholics showed an increasing trend from day 1 to day 3 and 4 of alcohol withdrawal. L-dopa administration raised salsolinol excretion in controls and withdrawn alcoholics to a uniform extent. Loading of the withdrawn alcoholics with an acute dose of alcohol did not cause an increase in urinary salsolinol concentration (despite increased plasma acetaldehyde). Indeed, 24 h following acute alcohol administration, salsolinol excretion rates were depressed in the alcoholics but not in the controls.

  10. Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity

    PubMed Central

    Greenberg, Gian D.; Phillips, Tamara J.; Crabbe, John C.

    2017-01-01

    Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4 g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24 h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10 h of withdrawal in WSR-1 females and to the initial 24 h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. PMID:27503811

  11. Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity.

    PubMed

    Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C

    2016-10-15

    Nest building has been used to assess thermoregulatory behavior and positive motivational states in mice. There are known genetic influences on ethanol withdrawal severity as well as individual/thermoregulatory nest building. Withdrawal Seizure-Prone (WSP-1, WSP-2) and Withdrawal Seizure-Resistant (WSR-1, WSR-2) mice were selectively bred for high vs low handling-induced convulsion (HIC) severity, respectively, during withdrawal from chronic ethanol vapor inhalation. They also differ in HIC severity during withdrawal from an acute, 4g/kg ethanol injection. In our initial study, withdrawal from an acute dose of ethanol dose-dependently impaired nest building over the initial 24h of withdrawal in genetically segregating Withdrawal Seizure Control (WSC) mice. In two further studies, acute ethanol withdrawal suppressed nest building for up to two days in WSP-1 females. Deficits in nest building from ethanol were limited to the initial 10h of withdrawal in WSR-1 females and to the initial 24h of withdrawal in WSP-1 and WSR-1 males. Effects of ethanol on nest building for up to two days were found in WSP-2 and WSR-2 mice of both sexes. Nest building deficits in female mice from the first replicate could not be explained by a general decrease in locomotor behavior. These results suggest that nest building is a novel behavioral phenotype for indexing the severity of acute ethanol withdrawal, and that genes contributing to this trait differ from those affecting acute withdrawal HIC severity. Published by Elsevier Inc.

  12. Acute Ethanol Withdrawal Impairs Contextual Learning and Enhances Cued Learning

    PubMed Central

    Tipps, Megan E.; Raybuck, Jonathan D.; Buck, Kari J.; Lattal, K. Matthew

    2014-01-01

    Background Alcohol affects many of the brain regions and neural processes that support learning and memory, and these effects are thought to underlie, at least in part, the development of addiction. Although much work has been done regarding the effects of alcohol intoxication on learning and memory, little is known about the effects of acute withdrawal from a single alcohol exposure. Methods We assess the effects of acute ethanol withdrawal (6 h post-injection with 4 g/kg ethanol) on two forms of fear conditioning (delay and trace fear conditioning) in C57BL/6J and DBA/2J mice. The influence of a number of experimental parameters (pre- and post-training withdrawal exposure; foreground/background processing; training strength; non-associative effects) is also investigated. Results Acute ethanol withdrawal during training had a bidirectional effect on fear conditioned responses, decreasing contextual responses and increasing cued responses. These effects were apparent for both trace and delay conditioning in DBA/2J mice and for trace conditioning in C57BL/6J mice; however, C57BL/6J mice were selectively resistant to the effects of acute withdrawal on delay cued responses. Conclusions Our results show that acute withdrawal from a single, initial ethanol exposure is sufficient to alter long-term learning in mice. In addition, the differences between the strains and conditioning paradigms used suggest that specific learning processes can be differentially affected by acute withdrawal in a manner that is distinct from the reported effects of both alcohol intoxication and withdrawal following chronic alcohol exposure. Thus, our results suggest a unique effect of acute alcohol withdrawal on learning and memory processes. PMID:25684050

  13. Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal

    PubMed Central

    Cunningham, Christopher L.; Fidler, Tara L.; Murphy, Kevin V.; Mulgrew, Jennifer A.; Smitasin, Phoebe J.

    2012-01-01

    Background Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Methods Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; non-dependent controls received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. Results The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7-9 h and returning to baseline within 24 h; withdrawal severity was greater in D2 than in B6 mice (Exp. 1). Post-withdrawal delays in initial ethanol access (1, 3 or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (Exp. 2). The post-withdrawal enhancement of ethanol intake persisted over a 5-d abstinence period in D2 mice (Exp. 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than non-dependent mice (Exp. 4). Conclusions Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. PMID:22999529

  14. Time-dependent negative reinforcement of ethanol intake by alleviation of acute withdrawal.

    PubMed

    Cunningham, Christopher L; Fidler, Tara L; Murphy, Kevin V; Mulgrew, Jennifer A; Smitasin, Phoebe J

    2013-02-01

    Drinking to alleviate the symptoms of acute withdrawal is included in diagnostic criteria for alcoholism, but the contribution of acute withdrawal relief to high alcohol intake has been difficult to model in animals. Ethanol dependence was induced by passive intragastric ethanol infusions in C57BL/6J (B6) and DBA/2J (D2) mice; nondependent control animals received water infusions. Mice were then allowed to self-administer ethanol or water intragastrically. The time course of acute withdrawal was similar to that produced by chronic ethanol vapor exposure in mice, reaching a peak at 7 to 9 hours and returning to baseline within 24 hours; withdrawal severity was greater in D2 than in B6 mice (experiment 1). Postwithdrawal delays in initial ethanol access (1, 3, or 5 days) reduced the enhancement in later ethanol intake normally seen in D2 (but not B6) mice allowed to self-infuse ethanol during acute withdrawal (experiment 2). The postwithdrawal enhancement of ethanol intake persisted over a 5-day abstinence period in D2 mice (experiment 3). D2 mice allowed to drink ethanol during acute withdrawal drank more ethanol and self-infused more ethanol than nondependent mice (experiment 4). Alcohol access during acute withdrawal increased later alcohol intake in a time-dependent manner, an effect that may be related to a genetic difference in sensitivity to acute withdrawal. This promising model of negative reinforcement encourages additional research on the mechanisms underlying acute withdrawal relief and its role in determining risk for alcoholism. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Nicotinic Mechanisms Modulate Ethanol Withdrawal and Modify Time Course and Symptoms Severity of Simultaneous Withdrawal from Alcohol and Nicotine.

    PubMed

    Perez, Erika; Quijano-Cardé, Natalia; De Biasi, Mariella

    2015-09-01

    Alcohol and nicotine are among the top causes of preventable death in the United States. Unfortunately, people who are dependent on alcohol are more likely to smoke than individuals in the general population. Similarly, smokers are more likely to abuse alcohol. Alcohol and nicotine codependence affects health in many ways and leads to poorer treatment outcomes in subjects who want to quit. This study examined the interaction of alcohol and nicotine during withdrawal and compared abstinence symptoms during withdrawal from one of the two drugs only vs both. Our results indicate that simultaneous withdrawal from alcohol and nicotine produces physical symptoms that are more severe and last longer than those experienced during withdrawal from one of the two drugs alone. In animals experiencing withdrawal after chronic ethanol treatment, acute nicotine exposure was sufficient to prevent abstinence symptoms. Similarly, symptoms were prevented when alcohol was injected acutely in mice undergoing nicotine withdrawal. These experiments provide evidence for the involvement of the nicotinic cholinergic system in alcohol withdrawal. Furthermore, the outcomes of intracranial microinfusions of mecamylamine, a nonselective nicotinic receptor antagonist, highlight a major role for the nicotinic receptors expressed in medial habenula and interpeduncular nucleus during withdrawal. Overall, the data support the notion that modulating the nicotinic cholinergic system might help to maintain long-term abstinence from alcohol.

  16. Combining the audit questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients.

    PubMed

    Dolman, Jonathan M; Hawkes, Neil D

    2005-01-01

    Alcohol consumption is often under-reported in patients admitted to general hospitals with acute illness. For alcohol-dependent individuals hospital admission results in an enforced period of abstinence with potential alcohol withdrawal symptoms, and possible life threatening complications. Early detection of alcohol use is therefore beneficial to patients and health services. The purpose of this study was to investigate the performance of the alcohol use disorders identification test (AUDIT) questionnaire in the acute medical setting, and the effect of combining routine biological markers-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and mean corpuscular volume (MCV) on its performance in the early identification of in-patients with alcohol use disorders and at risk of developing symptoms of alcohol withdrawal. Prospective study in consecutive patients admitted to an acute medical admissions ward. All patients were screened using the AUDIT questionnaire and routine blood tests. Patients were then monitored for symptoms of withdrawal using clinical institute withdrawal assessment for alcohol (CIWA-Ar). Of the 874 patients screened using the AUDIT, 98 (11%) screened positive of whom 17 (2% of the 874) experienced clinically significant alcohol withdrawal symptoms, when using serial CIWA-Ar. The AUDIT and serial CIWA-Ar detected all patients who went on to manifest acute withdrawal symptoms. There was no loss of sensitivity at an AUDIT cut-off of 13 or more compared with the lower cut-off of 8 or more. A positive predictive value of 17.3% for an AUDIT score of 8 or more in the detection of withdrawal, increased to 47.1% when found in combination with at least two abnormal biological markers whilst maintaining a sensitivity of 94.1% and specificity of 97.9%. These findings confirm that AUDIT is a useful alcohol screen in general medical settings and that its ability to correctly predict which patients will experience alcohol withdrawal is

  17. Review of adjunctive dexmedetomidine in the management of severe acute alcohol withdrawal syndrome.

    PubMed

    Wong, Adrian; Smithburger, Pamela L; Kane-Gill, Sandra L

    2015-01-01

    The primary management of alcohol withdrawal involves the administration of a γ-aminobutyric acid agonist, such as benzodiazepines, for management of symptoms and to prevent further progression to seizure or delirium tremens. Despite escalating doses of benzodiazepines, published literature indicates that some patient's alcohol withdrawal syndrome symptoms do not respond, and that the use of adjunctive agents may be beneficial in these patients. Dexmedetomidine, an α2-agonist, serves as a potential adjunctive agent through management of associated autonomic symptoms. Understanding of recent literature evaluating its use is necessary for appropriate selection. To review available literature supporting the use of adjunctive dexmedetomidine for management of severe alcohol withdrawal syndrome. A total of 13 published articles evaluating the efficacy and safety of dexmedetomidine as an adjunctive agent for the treatment of alcohol withdrawal in adult patients were identified from a MEDLINE search using the key words alcohol withdrawal, delirium tremens and dexmedetomidine. Evaluation of the literature indicates that dexmedetomidine is associated with a decrease in short-term benzodiazepine requirements after initiation, and improvement in hemodynamic parameters in relation to the adrenergic drive present in alcohol withdrawal. The use of dexmedetomidine in the management of severe alcohol withdrawal should be considered as an adjunctive agent. Dexmedetomidine appears to be well tolerated, with an expected decrease in blood pressure and heart rate. Seizures have occurred in patients with alcohol withdrawal despite the use of dexmedetomidine, with and without benzodiazepines, due to lack of γ-aminobutyric acid agonist administration.

  18. Heart rate variability and sympathetic skin response in male patients suffering from acute alcohol withdrawal syndrome.

    PubMed

    Bär, Karl-Jürgen; Boettger, Michael Karl; Neubauer, Rene; Grotelüschen, Marei; Jochum, Thomas; Baier, Vico; Sauer, Heinrich; Voss, Andreas

    2006-09-01

    Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients suffering from mild AW syndrome (n = 20, no treatment required) and in patients with moderate to severe AW syndrome (n = 20, clomethiazole treatment) in the acute stage. Sympathovagal influence was quantified using measures of time and frequency domain of HRV as well as modern nonlinear parameters (compression entropy). Furthermore, we obtained latencies and amplitudes of SSR to quantify isolated sympathetic influence. Measures were obtained during the climax of withdrawal symptomatology before treatment, 1 day after climax, and shortly before discharge from hospital. Alcohol withdrawal scores were obtained and correlated to autonomic measures. Ambulatory blood pressure and AW scores revealed characteristic withdrawal symptoms in both patient groups. Apart from the nonlinear parameter compression entropy, Hc, measures of HRV revealed no sign of autonomic dysfunction in contrast to the significantly increased heart rates at the time of admission. Latencies and amplitudes of SSR did not indicate any increase of sympathetic activity. A negative correlation was found between Hc and mental withdrawal symptoms. We show here that classical measures for autonomic nervous system activity such as HRV and SSR are not suitable for describing the autonomic changes seen in acute AW, although a major role for the sympathetic nervous system has been proposed. This might be due to multiple dysregulation of metabolites in AWS or to subtle alcohol-induced damage to neuronal structures, issues that should be addressed in future studies.

  19. Tobacco smoking interferes with GABAA receptor neuroadaptations during prolonged alcohol withdrawal

    PubMed Central

    Cosgrove, Kelly P.; McKay, Reese; Esterlis, Irina; Kloczynski, Tracy; Perkins, Evgenia; Bois, Frederic; Pittman, Brian; Lancaster, Jack; Glahn, David C.; O’Malley, Stephanie; Carson, Richard E.; Krystal, John H.

    2014-01-01

    Understanding the effects of tobacco smoking on neuroadaptations in GABAA receptor levels over alcohol withdrawal will provide critical insights for the treatment of comorbid alcohol and nicotine dependence. We conducted parallel studies in human subjects and nonhuman primates to investigate the differential effects of tobacco smoking and nicotine on changes in GABAA receptor availability during acute and prolonged alcohol withdrawal. We report that alcohol withdrawal with or without concurrent tobacco smoking/nicotine consumption resulted in significant and robust elevations in GABAA receptor levels over the first week of withdrawal. Over prolonged withdrawal, GABAA receptors returned to control levels in alcohol-dependent nonsmokers, but alcohol-dependent smokers had significant and sustained elevations in GABAA receptors that were associated with craving for alcohol and cigarettes. In nonhuman primates, GABAA receptor levels normalized by 1 mo of abstinence in both groups—that is, those that consumed alcohol alone or the combination of alcohol and nicotine. These data suggest that constituents in tobacco smoke other than nicotine block the recovery of GABAA receptor systems during sustained alcohol abstinence, contributing to alcohol relapse and the perpetuation of smoking. PMID:25453062

  20. Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

    PubMed Central

    Dreumont, Sarah E.; Cunningham, Christopher L.

    2013-01-01

    Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

  1. Anticonvulsants for the treatment of alcohol withdrawal syndrome and alcohol use disorders.

    PubMed

    Hammond, Christopher J; Niciu, Mark J; Drew, Shannon; Arias, Albert J

    2015-04-01

    Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.

  2. Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

    PubMed Central

    Hammond, Christopher J.; Niciu, Mark J.; Drew, Shannon; Arias, Albert J.

    2015-01-01

    Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders. PMID:25895020

  3. Anticonvulsants for alcohol withdrawal.

    PubMed

    Minozzi, Silvia; Amato, Laura; Vecchi, Simona; Davoli, Marina

    2010-03-17

    Alcohol abuse and dependence represents a most serious health problem worldwide with major social, interpersonal and legal interpolations. Besides benzodiazepines, anticonvulsants are often used for the treatment of alcohol withdrawal symptoms. Anticonvulsants drugs are indicated for the treatment of alcohol withdrawal syndrome, alone or in combination with benzodiazepine treatments. In spite of the wide use, the exact role of the anticonvulsants for the treatment of alcohol withdrawal has not yet bee adequately assessed. To evaluate the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal. We searched Cochrane Drugs and Alcohol Group' Register of Trials (December 2009), PubMed, EMBASE, CINAHL (1966 to December 2009), EconLIT (1969 to December 2009). Parallel searches on web sites of health technology assessment and related agencies, and their databases. Randomized controlled trials (RCTs) examining the effectiveness, safety and overall risk-benefit of anticonvulsants in comparison with a placebo or other pharmacological treatment. All patients were included regardless of age, gender, nationality, and outpatient or inpatient therapy. Two authors independently screened and extracted data from studies. Fifty-six studies, with a total of 4076 participants, met the inclusion criteria. Comparing anticonvulsants with placebo, no statistically significant differences for the six outcomes considered.Comparing anticonvulsant versus other drug, 19 outcomes considered, results favour anticonvulsants only in the comparison carbamazepine versus benzodiazepine (oxazepam and lorazepam) for alcohol withdrawal symptoms (CIWA-Ar score): 3 studies, 262 participants, MD -1.04 (-1.89 to -0.20), none of the other comparisons reached statistical significance.Comparing different anticonvulsants no statistically significant differences in the two outcomes considered.Comparing anticonvulsants plus other drugs versus other drugs (3 outcomes considered), results

  4. Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

    PubMed Central

    Richey, Laura; Doremus-Fitzwater, Tamara L.; Buck, Hollin M.; Deak, Terrence

    2012-01-01

    Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100 μg/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5 g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed. PMID

  5. Alcohol Withdrawal Syndrome: Benzodiazepines and Beyond

    PubMed Central

    Sachdeva, Ankur; Chandra, Mina

    2015-01-01

    Alcohol dependence is an increasing and pervasive problem. Alcohol withdrawal symptoms are a part of alcohol dependence syndrome and are commonly encountered in general hospital settings, in most of the departments. Alcohol withdrawal syndrome ranges from mild to severe. The severe complicated alcohol withdrawal may present with hallucinations, seizures or delirium tremens. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal, and are considered the gold standard. Others, such as anticonvulsants, barbiturates, adrenergic drugs, and GABA agonists have been tried and have evidence. Supportive care and use of vitamins is essential in the management. Symptom triggered regime is favoured over fixed tapering dose regime, although monitoring through scales is cumbersome. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on ‘Alcohol withdrawal syndrome’ in humans during the last 10 years. A total of 1182 articles came up. Articles not relevant to clinical utility and management were excluded based on the titles and abstract available. Full text articles, meta-analyses, systematic reviews and randomized controlled trials were obtained from this list and were considered for review. PMID:26500991

  6. Diverse autonomic regulation of pupillary function and the cardiovascular system during alcohol withdrawal.

    PubMed

    Jochum, Thomas; Hoyme, Johannes; Schulz, Steffen; Weißenfels, Markus; Voss, Andreas; Bär, Karl-Jürgen

    2016-02-01

    Previous research indicated the complexity of autonomic dysfunction during acute alcohol withdrawal. This study aimed to investigate the pupillary light reflex as an indicator of midbrain and brainstem regulatory systems in relation to cardiovascular autonomic function. Thirty male patients were included in the study. They were investigated during acute alcohol withdrawal syndrome and 24h later during clomethiazole treatment and compared to healthy controls. Parameters of pupillary light reflex of both eyes as well as heart rate variability, blood pressure variability and baroreflex sensitivity (BRS) were studied. We observed significantly reduced sympathetic (small diameter, e.g., left eye: 5.00 in patients vs. 5.91 mm in controls) and vagal modulation (e.g., prolonged latencies, left eye: 0.28 vs. 0.26 ms) regarding both pupils during acute alcohol withdrawal syndrome. Cardiovascular parameters showed reduced vagal modulation (e.g., b-slope of BRS: 7. 57 vs. 13.59 ms/mm Hg) and mixed results for sympathetic influence. After 24h, autonomic dysfunction improved significantly, both for the pupils (e.g., left diameter: 5.38 mm) and the heart (e.g., b-slope of BRS: 9.34 ms/mm Hg). While parameters obtained from the pupil correlated with cardiac autonomic function (e.g, BRS and left diameter: r=0.564) in healthy controls, no such pattern was observed in patients. Results obtained from the pupil during acute alcohol withdrawal do not simply mirror autonomic dysfunction regarding the heart. Pupillary and cardiovascular changes after 24h indicate state dependencies of the results. The findings are discussed with respect to autonomic mechanisms and potentially involved brain regions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Alcohol withdrawal

    MedlinePlus

    ... Seeing or feeling things that aren't there (hallucinations) Seizures Severe confusion ... alcohol withdrawal. You will be watched closely for hallucinations and other signs of delirium tremens. Treatment may ...

  8. Cardiovascular Events in Alcoholic Syndrome With Alcohol Withdrawal History: Results From the National Inpatient Sample.

    PubMed

    Krishnamoorthy, Parasuram; Kalla, Aditi; Figueredo, Vincent M

    2018-05-01

    Epidemiologic studies suggest reduced cardiovascular disease (CVD) events with moderate alcohol consumption. However, heavy and binge drinking may be associated with higher CVD risk. Utilizing the Nationwide Inpatient Sample, we studied the association between a troublesome alcohol history (TAH), defined as those with diagnoses of both chronic alcohol syndrome and acute withdrawal history and CVD events. Patients >18 years with diagnoses of both chronic alcohol syndrome and acute withdrawal using the International Classification of Diseases-Ninth Edition-Clinical Modification (ICD-9-CM) codes 303.9 and 291.81, were identified in the Nationwide Inpatient Sample 2009-2010 database. Demographics, including age and sex, as well as CVD event rates were collected. Patients with TAH were more likely to be male, with a smoking history and have hypertension, with less diabetes, hyperlipidemia and obesity. After multimodal adjusted regression analysis, odds of coronary artery disease, acute coronary syndrome, in-hospital death and heart failure were significantly lower in patients with TAH when compared to the general discharge patient population. Utilizing a large inpatient database, patients with TAH had a significantly lower prevalence of CVD events, even after adjusting for demographic and traditional risk factors, despite higher tobacco use and male sex predominance, when compared to the general patient population. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  9. Inpatient alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Rabuñal-Rey, R; Guerrero-Sande, H

    2015-03-01

    A 55-year-old man was admitted for a femur fracture; an alcohol fetor was noted on admission. The following day, the patient began to experience tremors and nervousness. Intravenous haloperidol was administered. Shortly afterwards, the patient experienced two generalized seizures and then began to experience delirium and uncontrollable agitation. The patient was diagnosed with alcohol withdrawal syndrome; high doses of intravenous midazolam were prescribed and infused. A few hours later, the patient presented signs of respiratory depression, requiring a transfer to the intensive care unit. After a review of the medical history, it was determined that the patient had been admitted on 3 previous occasions due to alcohol withdrawal and had progressed to delirium tremens after experiencing seizures. Can the risk of alcohol withdrawal syndrome and the need for prophylactic treatment be assessed on admission? Were appropriate monitoring and treatment measures employed? Would it have been possible to change his outcome? Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  10. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of fuel alcohol. 19.729 Section 19.729 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU..., Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or other...

  11. 27 CFR 19.729 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Withdrawal of fuel alcohol..., DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Distilled Spirits for Fuel Use Rules for Use, Withdrawal, and Transfer of Spirits § 19.729 Withdrawal of fuel alcohol. (a) For each shipment or other...

  12. Development of an alcohol withdrawal protocol: CNS collaborative exemplar.

    PubMed

    Phillips, Susan; Haycock, Camille; Boyle, Deborah

    2006-01-01

    The purpose of this process improvement project was to develop an Alcohol Withdrawal Syndrome (AWS) management protocol for acute care. The prevalence of alcohol abuse in our society presents challenges for health professionals, and few nurses have received formal education on the identification and treatment of AWS, which has frequently resulted in ineffective, nonstandardized care. However, nurses practicing in medical-surgical, emergency, trauma, and critical care settings must be astute in the assessment and management of AWS. DESIGN/BACKGROUND/RATIONALE: Following an analysis of existing management protocols, a behavioral health clinical nurse specialist was asked to lead a work team composed of physicians, pharmacists, and nurses to develop a new evidence-based alcohol withdrawal protocol for acute care. By implementing a standardized assessment tool and treatment protocol, clinical nurse specialists empowered nursing staff with strategies to prevent the serious medical complications associated with AWS. FINDINGS/OUTCOMES: The development and integration of a safe and effective treatment protocol to manage AWS was facilitated by collaborative, evidence-based decision making. Clinical experience and specialty expertise were integrated by clinical nurse specialists skilled in group dynamics, problem-solving, and the implementation of change. Improving care of patients in AWS is an exemplar for clinical nurse specialist roles as change agent and patient advocate.

  13. Dexmedetomidine infusion as adjunctive therapy to benzodiazepines for acute alcohol withdrawal.

    PubMed

    Darrouj, Jamil; Puri, Nitin; Prince, Erin; Lomonaco, Anthony; Spevetz, Antoinette; Gerber, David R

    2008-11-01

    To report a case of alcohol withdrawal and delirium tremens successfully treated with adjunctive dexmedetomidine. A 30-year-old man with a history of alcohol abuse was admitted to the general medical unit because of altered mental status and agitation. He was initially treated for alcohol withdrawal with benzodiazepines; his condition then deteriorated and he was transferred to the intensive care unit. Because of the patient's poor response to benzodiazepines (oxazepam and lorazepam, with midazolam the last one used), intravenous dexmedetomidine was started at an initial dose of 0.2 microg/kg/h and titrated to 0.7 microg/kg/h to the patient's comfort. Midazolam was subsequently tapered to discontinuation due to excessive sedation. In the intensive care unit, the patient's symptoms remained controlled with use of dexmedetomidine alone. He remained in the intensive care unit for 40 hours; dexmedetomidine was then tapered to discontinuation and the patient was transferred back to the general medical unit on oral oxazepam and thiamine, which had been started in the emergency department. He was discharged after 5 days. A review of the PubMed database (1989-2007) failed to identify any other instances of dexmedetomidine having been used as the principal agent to treat alcohol withdrawal. The use of sedative to treat delirium tremens is well documented, with benzodiazepines being the agents of choice. The clinical utility of benzodiazepines is limited by their stimulation of the gamma-aminobutyric acid receptors, an effect not shared by dexmedetomidine, a central alpha(2)-receptor agonist that induces a state of cooperative sedation and does not suppress respiratory drive. In patients with delirium tremens, dexmedetomidine should be considered as an option for primary treatment. This case illustrates the need for further studies to investigate other potential uses for dexmedetomidine.

  14. 27 CFR 19.997 - Withdrawal of fuel alcohol.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of fuel alcohol. 19.997 Section 19.997 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... and Transfers § 19.997 Withdrawal of fuel alcohol. For each shipment or other removal of fuel alcohol...

  15. IDENTIFICATION AND MANAGEMENT OF ALCOHOL WITHDRAWAL SYNDROME

    PubMed Central

    Mirijello, Antonio; D’Angelo, Cristina; Ferrulli, Anna; Vassallo, Gabriele; Antonelli, Mariangela; Caputo, Fabio; Leggio, Lorenzo; Gasbarrini, Antonio; Addolorato, Giovanni

    2016-01-01

    Symptoms of alcohol withdrawal syndrome may develop within 6–24 hours after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for alcohol withdrawal syndrome is represented by benzodiazepines. Among them, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as alpha2-agonists (clonidine and dexmetedomidine) and beta-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptics can help control hallucinations. Finally, other medications for the treatment for alcohol withdrawal syndrome have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin, and topiramate. The usefulness of these agents will be discussed in the text. PMID:25666543

  16. Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.

    PubMed

    Xiao, Hui-Wen; Ge, Chang; Feng, Guo-Xing; Li, Yuan; Luo, Dan; Dong, Jia-Li; Li, Hang; Wang, Haichao; Cui, Ming; Fan, Sai-Jun

    2018-05-01

    Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  17. Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats.

    PubMed

    Dencker, Ditte; Molander, Anna; Thomsen, Morgane; Schlumberger, Chantal; Wortwein, Gitta; Weikop, Pia; Benveniste, Helene; Volkow, Nora D; Fink-Jensen, Anders

    2018-02-01

    Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls. Given the switch of metabolic fuel from glucose to acetate in the alcohol-dependent brain, we investigated the potential therapeutic benefit of a ketogenic diet in managing alcohol withdrawal symptoms during detoxification. Male Sprague Dawley rats fed either ketogenic or regular diet were administered ethanol or water orally, twice daily for 6 days while the diet conditions were maintained. Abstinence symptoms were rated 6, 24, 48, and 72 hours after the last alcohol administration. Maintenance on a ketogenic diet caused a significant decrease in the alcohol withdrawal symptoms' "rigidity" and "irritability." Our preclinical pilot study suggests that a ketogenic diet may be a novel approach for treating alcohol withdrawal symptoms in humans. Copyright © 2017 by the Research Society on Alcoholism.

  18. Acupuncture for alcohol withdrawal: a randomized controlled trial.

    PubMed

    Trümpler, François; Oez, Suzan; Stähli, Peter; Brenner, Hans Dieter; Jüni, Peter

    2003-01-01

    Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.

  19. [Alcohol withdrawal syndrome dynamics during treatment with nooclerin (deanoli aceglumas)].

    PubMed

    Agibalova, T V; Buzik, O Zh; Rychkova, O V; Smyshlyaev, A V; Rumbesht, V V

    2018-01-01

    To study the efficacy of nooclerin (deanoli aceglumas) in alcohol withdrawal syndrome assessed by clinical and biochemical characteristics. A multicenter, open, randomized, comparative study of nooclerin in the complex treatment of alcohol withdrawal syndrome included 90 patients. The patients were randomized into nooclerin group (n=55) and control group (n=35). Nooclerin reduced alcohol withdrawal symptoms more significantly throughout the whole study period. There were significant between-group differences on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) and the Multidimensional Fatigue Inventory (МFI-20). However, patients exhibited no excessive activity. No adverse side-effects were observed.

  20. Phenobarbital compared to benzodiazepines in alcohol withdrawal treatment: A register-based cohort study of subsequent benzodiazepine use, alcohol recidivism and mortality.

    PubMed

    Askgaard, Gro; Hallas, Jesper; Fink-Jensen, Anders; Molander, Anna Camilla; Madsen, Kenneth Grønkjær; Pottegård, Anton

    2016-04-01

    Long-acting benzodiazepines such as chlordiazepoxide are recommended as first-line treatment for alcohol withdrawal. These drugs are known for their abuse liability and might increase alcohol consumption among problem drinkers. Phenobarbital could be an alternative treatment option, possibly with the drawback of a more pronounced acute toxicity. We evaluated if phenobarbital compared to chlordiazepoxide decreased the risk of subsequent use of benzodiazepines, alcohol recidivism and mortality. The study was a register-based cohort study of patients admitted for alcohol withdrawal 1998-2013 and treated with either phenobarbital or chlordiazepoxide. Patients were followed for one year. We calculated hazard ratios (HR) for benzodiazepine use, alcohol recidivism and mortality associated with alcohol withdrawal treatment, while adjusting for confounders. A total of 1063 patients treated with chlordiazepoxide and 1365 patients treated with phenobarbital were included. After one year, the outcome rates per 100 person-years in the phenobarbital versus the chlordiazepoxide cohort were 9.20 vs. 5.13 for use of benzodiazepine, 37.9 vs. 37.9 for alcohol recidivism and 29 vs. 59 for mortality. Comparing phenobarbital to chlordiazepoxide treated, the HR of subsequent use of benzodiazepines was 1.56 (95%CI 1.05-2.30). Similarly, the HR for alcohol recidivism was 0.99 (95%CI 0.84-1.16). Lastly, the HR for 30-days and 1 year mortality was 0.25 (95%CI 0.08-0.78) and 0.51 (95%CI 0.31-0.86). There was no decreased risk of subsequent benzodiazepine use or alcohol recidivism in patients treated with phenobarbital compared to chlordiazepoxide. Phenobarbital treatment was associated with decreased mortality, which might be confounded by somatic comorbidity among patients receiving chlordiazepoxide. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Alcohol withdrawal management in adult patients in a high acuity medical surgical transitional care unit: a best practice implementation project.

    PubMed

    Sukhenko, Olga

    2016-01-15

    implemented this criterion recorded an improvement to 100% compliance. None of the patients in the pilot were transferred to the intensive care unit (ICU) for reasons relating to alcohol withdrawal. The outcomes of this project demonstrated alcohol withdrawal management can be safely undertaken outside the ICU when the patients are appropriately assessed and treated for the severity of their withdrawal symptoms. This new clinical program significantly impacted on continuity of care. Challenges were resolved using an interdisciplinary team approach. The project resulted in plans for further areas of work concerning alcohol withdrawal management, including adoption of similar approaches by other acute and transitional care units. The Joanna Briggs Institute.

  2. Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles.

    PubMed

    Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M; Ryabinin, Andrey E

    2018-03-27

    The expression of pain serves as a way for animals to communicate potential dangers to nearby conspecifics. Recent research demonstrated that mice undergoing alcohol or morphine withdrawal, or inflammation, could socially communicate their hyperalgesia to nearby mice. However, it is unknown whether such social transfer of hyperalgesia can be observed in other species of rodents. Therefore, the present study investigated if the social transfer of hyperalgesia occurs in the highly social prairie vole (Microtus ochrogaster). We observe that adult female prairie voles undergoing withdrawal from voluntary two-bottle choice alcohol drinking display an increase in nociception. This alcohol withdrawal-induced hypersensitiity is socially transferred to female siblings within the same cage and female strangers housed in separate cages within the same room. These experiments reveal that the social transfer of pain phenomenon is not specific to inbred mouse strains and that prairie voles display alcohol withdrawal and social transfer-induced hyperalgesia.

  3. Baclofen for alcohol withdrawal.

    PubMed

    Liu, Jia; Wang, Lu-Ning

    2017-08-20

    Baclofen shows potential for rapidly reducing symptoms of severe alcohol withdrawal syndrome (AWS) in people with alcoholism. Treatment with baclofen is easy to manage and rarely produces euphoria or other pleasant effects, or craving for the drug. This is an updated version of the original Cochrane Review published in 2015, Issue 4. To assess the efficacy and safety of baclofen for people with AWS. We updated our searches of the following databases to March 2017: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, PubMed, Embase, and CINAHL. We also searched registers of ongoing trials. We handsearched the references quoted in the identified trials, and sought information from researchers, pharmaceutical companies, and relevant trial authors about unpublished or uncompleted trials. We placed no restrictions on language. We included all randomised controlled clinical trials (RCTs) evaluating baclofen versus placebo or any other treatment for people with AWS. We excluded uncontrolled, non-randomised, or quasi-randomised trials. We included both parallel group and cross-over studies. We used standard methodological procedures expected by Cochrane. We included three RCTs with 141 randomised participants. We did not perform meta-analyses due to the different control interventions. For the comparison of baclofen and placebo (1 study, 31 participants), there was no significant difference in Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) scores (very low quality evidence). For the comparison of baclofen and diazepam (1 study, 37 participants), there was no significant difference in CIWA-Ar scores (very low quality evidence), adverse events (risk difference (RD) 0.00, 95% confidence interval (CI) -0.10 to 0.10; very low quality evidence), dropouts (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence), and dropouts due to adverse events (RD 0.00, 95% CI -0.10 to 0.10; very low quality evidence). For the comparison of

  4. DIFFERENTIAL EFFECTS OF SINGLE VERSUS REPEATED ALCOHOL WITHDRAWAL ON THE EXPRESSION OF ENDOCANNABINOID SYSTEM-RELATED GENES IN THE RAT AMYGDALA

    PubMed Central

    Serrano, Antonia; Rivera, Patricia; Pavon, Francisco J.; Decara, Juan; Suárez, Juan; de Fonseca, Fernando Rodriguez; Parsons, Loren H.

    2011-01-01

    Background Endogenous cannabinoids such as anandamide and 2-arachidonoylglycerol (2-AG) exert important regulatory influences on neuronal signaling, participate in short- and long-term forms of neuroplasticity, and modulate stress responses and affective behavior in part through the modulation of neurotransmission in the amygdala. Alcohol consumption alters brain endocannabinoid levels, and alcohol dependence is associated with dysregulated amygdalar function, stress responsivity and affective control. Methods The consequence of long-term alcohol consumption on the expression of genes related to endocannabinoid signaling was investigated using quantitative RT-PCR analyses of amygdala tissue. Two groups of ethanol-exposed rats were generated by maintenance on an ethanol liquid diet (10%): one group received continuous access to ethanol for 15 days, while the second group was given intermittent access to the ethanol diet (5 days/week for 3 weeks). Control subjects were maintained on an isocaloric ethanol-free liquid diet. To provide an initial profile of acute withdrawal amygdala tissue was harvested following either 6 or 24 hours of ethanol withdrawal. Results Acute ethanol withdrawal was associated with significant changes in mRNA expression for various components of the endogenous cannabinoid system in the amygdala. Specifically, reductions in mRNA expression for the primary clearance routes for anandamide and 2-AG (FAAH and MAGL, respectively) were evident, as were reductions in mRNA expression for CB1, CB2 and GPR55 receptors. Although similar alterations in FAAH mRNA were evident following either continuous or intermittent ethanol exposure, alterations in MAGL and cannabinoid receptor-related mRNA (e.g. CB1, CB2, GPR55) were more pronounced following intermittent exposure. In general, greater withdrawal-associated deficits in mRNA expression were evident following 24 versus 6 hours of withdrawal. No significant changes in mRNA expression for enzymes involved in

  5. [Clinical Practice Guide for Early Detection, Diagnosis and Treatment of the Acute Intoxication Phase in Patients with Alcohol Abuse or Dependence: Part II: Evaluation and Management of Patients with Acute Alcohol Intoxication].

    PubMed

    de la Espriella Guerrero, Ricardo; de la Hoz Bradford, Ana María; Zárate, Alina Uribe-Holguín; Lee, Patricia Rodríguez; Menéndez, Miguel Cote; Rentería, Ana María Cano; Hernández, Delia Cristina; Cardeño, Carlos; Barré, Michelle Cortés; Kunzel, Gabriel Hernández; Gómez-Restrepo, Carlos

    2012-12-01

    Worldwide, alcohol is the second most-used psychotropic substance and the third risk factor for early death and disability. Its noxious use is a world public health problem given its personal, labor, family, economic and social impact. The identification of acute alcohol intoxication is extremely important, as well as the alcohol withdrawal syndrome and its complications, such as delirium tremens and Wernicke's encephalopathy in order to grant a timely treatment for those patients. This article introduces the evidence found so as to face and treat these clinic manifestations. Systematic revision of the evidence available together with an evaluation of pertinent guidelines found in literature so as to decide whether to adopt or adapt the existing recommendation for each question or to develop de novo recommendations. For de novo recommendations as well as those adapted, it was carried out an evidence synthesis, together with evidence tables and formulation of recommendations based on the evidence. Evidence was found and recommendations were made for the diagnosis and treatment of acute alcohol intoxication, withdrawal syndrome, delirium tremens and Wernicke's encephalopathy. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  6. Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

    PubMed Central

    Farook, Justin M.; Krazem, Ali; Littleton, John M.; Barron, Susan

    2008-01-01

    In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p’s < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p’s < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence. PMID:18577392

  7. Alcohol withdrawal syndrome: symptom-triggered versus fixed-schedule treatment in an outpatient setting.

    PubMed

    Elholm, Bjarne; Larsen, Klaus; Hornnes, Nete; Zierau, Finn; Becker, Ulrik

    2011-01-01

    To investigate whether, in the treatment with chlordiazepoxide for outpatient alcohol withdrawal, there are advantages of symptom-triggered self-medication over a fixed-schedule regimen. A randomized controlled trial in outpatient clinics for people suffering from alcohol dependence (AD) and alcohol-related problems; 165 adult patients in an outpatient setting in a specialized alcohol treatment unit were randomized 1:1 to either a symptom-triggered self-medication or tapered dose, using chlordiazepoxide. Alcohol withdrawal symptoms, amount of medication, duration of symptoms, time to relapse and patient satisfaction were measured. Patients assessed their symptoms using the Short Alcohol Withdrawal Scale (SAWS). Patient satisfaction was monitored by the Diabetes Treatment Satisfaction Questionnaire. We used the Well-Being Index and the European addiction severity index for the 1-year follow-up. We found no differences in the quantity of medication consumed, time to relapse, well being or treatment satisfaction. Symptom-triggered self-medication was as safe as fixed-schedule medication in treating outpatients with AD and mild to moderate symptoms of AWS. The SAWS is a powerful monitoring tool, because it is brief and permits the subject to log the withdrawal symptoms.

  8. [Treatment of Alcohol Withdrawal Syndrome with Oxazepam or Clomethiazole - A Naturalistic Observational Study].

    PubMed

    Verthein, Uwe; Kuhn, Silke; Gabriel, Katrin; Mautsch, Ulrich; Reimer, Jens; Behrendt, Klaus

    2018-03-01

    Whilst internationally benzodiazepines are first choice for treatment of alcohol withdrawal syndrome, Germany has a long tradition with clomethiazole. This study explores effectiveness of clomethiazole versus oxazepam in the treatment of alcohol withdrawal syndrome within an observational, stratified, non-inferiority study in routine care. Main outcome criterion was severity of the alcohol withdrawal syndrome (Alcohol Withdrawal Syndrome [AWS]) Scale in the first five days. Additionally, the association between the detoxification protocol (five vs. ten days) and AWS-Score was examined. 453 patients (74.2 % male, average age 47.1 years [± 9.2]) took part; 249 received oxazepam (55.0 %) and 204 clomethiazole (45.0 %). The average duration of inpatient treatment was 14.0 days (± 6.3) in both groups. The average AWS-score was lower in the oxazepam group compared to the clomethiazole group (50.0 [± 26.5] vs. 56.2 [± 31.5]; p < .05; effect size d = - .25). Patients with a shorter detoxification protocol had a lower AWS sum score compared to patients with a longer protocol (p < .001; d = - .46). In treatment of alcohol withdrawal syndrome in routine care oxazepam yields at least comparable results to clomethiazole. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Standardized Passiflora incarnata L. Extract Reverts the Analgesia Induced by Alcohol Withdrawal in Rats.

    PubMed

    Schunck, Rebeca Vargas Antunes; Macedo, Isabel Cristina; Laste, Gabriela; de Souza, Andressa; Valle, Marina Tuerlinckx Costa; Salomón, Janaína L O; Nunes, Ellen Almeida; Campos, Andreia Cristina Wildner; Gnoatto, Simone Cristina Baggio; Bergold, Ana Maria; Konrath, Eduardo L; Dallegrave, Eliane; Arbo, Marcelo Dutra; Torres, Iraci L S; Leal, Mirna Bainy

    2017-08-01

    Passiflora incarnata L. (Passifloraceae) has been traditionally used for treatment of anxiety, insomnia, drug addiction, mild infections, and pain. The aim of this study was to investigate the effect of a commercial extract of P. incarnata in the analgesia induced by alcohol withdrawal syndrome in rats. In addition, brain-derived neurotrophic factor and interleukin-10 levels were evaluated in prefrontal cortex, brainstem, and hippocampus. Male adult rats received by oral gavage: (1: water group) water for 19 days, 1 day interval and water (8 days); (2: P. incarnata group) water for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days); (3: alcohol withdrawal group) alcohol for 19 days, 1 day interval and water (8 days); and (4: P. incarnata in alcohol withdrawal) alcohol for 19 days, 1 day interval and P. incarnata 200 mg/kg (8 days). The tail-flick and hot plate tests were used as nociceptive response measures. Confirming previous study of our group, it was showed that alcohol-treated groups presented an increase in the nociceptive thresholds after alcohol withdrawal, which was reverted by P. incarnata, measured by the hot plate test. Besides, alcohol treatment increased brain-derived neurotrophic factor and interleukin-10 levels in prefrontal cortex, which was not reverted by P. incarnata. Considering these results, the P. incarnata treatment might be a potential therapy in the alcohol withdrawal syndrome. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice.

    PubMed

    Metten, Pamela; Schlumbohm, Jason P; Huang, Lawrence C; Greenberg, Gian D; Hack, Wyatt R; Spence, Stephanie E; Crabbe, John C

    2018-05-01

    Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes. Published by Elsevier Inc.

  11. Taurine restores the exploratory behavior following alcohol withdrawal and decreases BDNF mRNA expression in the frontal cortex of chronic alcohol-treated rats.

    PubMed

    Hansen, Alana Witt; Almeida, Felipe Borges; Bandiera, Solange; Pulcinelli, Rianne Remus; Fragoso, Ana Luiza Rodrigues; Schneider, Ricardo; Barros, Helena Maria Tannhauser; Gomez, Rosane

    2017-10-01

    Alcohol use disorder is an alarming health problem, and the withdrawal symptoms increase the risk of relapse. We have hypothesized that taurine, a multitarget substance acting as a gamma-aminobutyric acid A receptor (GABA A R) positive modulator and a partial inhibitor of N-methyl-d-aspartate (NMDA) glutamate receptors, may reduce the withdrawal symptoms or modify behaviors when combined with alcohol. Therefore, we investigated the effects of taurine on behavior in the open field test (OFT), the GABA A R α 2 subunit and BDNF mRNA expression in the frontal cortex of rats after chronic alcohol treatment or upon withdrawal. Rats received alcohol 2g/kg (alcohol and withdrawal groups) or water (control group) twice daily by oral gavage for 28days. On day 29, the withdrawal rats received water instead of alcohol, and all groups were reallocated to receive 100mg/kg taurine or vehicle intraperitoneally, once a day for 5days. On day 33, the rats were exposed to OFT; 18h later, they were euthanized, and the frontal cortex was dissected for GABA A R α 2 subunit detection and BDNF mRNA expression determination by real-time quantitative PCR. Taurine administration restored rearing behavior to the control levels in the withdrawal rats. Taurine also showed anxiolytic-like effects in control rats and did not change the behaviors in the chronic alcohol group. Chronic alcohol treatment or withdrawal did not change the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex, but taurine decreased the α 2 subunit level in control rats and to the BDNF levels in the alcohol rat group. We conclude that taurine restored exploratory behavior after alcohol withdrawal but that this effect was not related to the GABA A R α 2 subunit or BDNF mRNA expression in the frontal cortex of the rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Unsuspected Critical Illness Among Emergency Department Patients Presenting for Acute Alcohol Intoxication.

    PubMed

    Klein, Lauren R; Cole, Jon B; Driver, Brian E; Battista, Christopher; Jelinek, Ryan; Martel, Marc L

    2018-03-01

    Emergency department (ED) visits for acute alcohol intoxication are common, but this population is at risk for decompensation and occult critical illness. The purpose of this study is to describe the incidence and predictors of unsuspected critical illness among patients with acute alcohol intoxication. This was a retrospective observational study of ED patients from 2011 to 2016 with acute alcohol intoxication. The study cohort included patients presenting for alcohol intoxication, whose initial assessment was uncomplicated alcohol intoxication without any other active acute medical or traumatic complaints. The primary outcome was defined as the unanticipated subsequent use of critical care resources during the encounter or admission to an ICU. We investigated potential predictors for this outcome with generalized estimating equations. We identified 31,364 eligible patient encounters (median age 38 years; 71% men; median breath alcohol concentration 234 mg/dL); 325 encounters (1%) used critical care resources. The most common diagnoses per 1,000 ED encounters were acute hypoxic respiratory failure (3.1), alcohol withdrawal (1.7), sepsis or infection (1.1), and intracranial hemorrhage (1.0). Three patients sustained a cardiac arrest. Presence of the following had an increased adjusted odds ratio (aOR) of developing critical illness: hypoglycemia (aOR 9.2), hypotension (aOR 3.8), tachycardia (aOR 1.8), fever (aOR 7.6), hypoxia (aOR 3.8), hypothermia (aOR 4.2), and parenteral sedation (aOR 2.4). The initial blood alcohol concentration aOR was 1.0. Critical care resources were used for 1% of ED patients with alcohol intoxication who were initially assessed by physicians to have low risk. Abnormal vital signs, hypoglycemia, and chemical sedation were associated with increased odds of critical illness. Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  13. Infant emotional withdrawal: a precursor of affective and cognitive disturbance in fetal alcohol spectrum disorders.

    PubMed

    Molteno, Christopher D; Jacobson, Joseph L; Carter, R Colin; Dodge, Neil C; Jacobson, Sandra W

    2014-02-01

    Our aim was to test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Sociodemographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years, cognitive and affective function at 5 and 9 years. Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy. These data link

  14. Management of acute overdose or withdrawal state in intrathecal baclofen therapy.

    PubMed

    Watve, S V; Sivan, M; Raza, W A; Jamil, F F

    2012-02-01

    Individuals who are treated with intrathecal Baclofen (ITB) pump delivery system for intractable spasticity can suffer from severe morbidity as a result of acute overdose or withdrawal of ITB, which can also be life threatening. Current literature has a number of single case studies with different approaches to the management in such states. The aim of this article is to consolidate available evidence and develop treatment pathways for acute ITB overdose and withdrawal states. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library databases using the keywords 'intrathecal', 'baclofen', 'withdrawal', 'overdose' to identify studies (published up to December 2010) that focused on presentation or treatment of acute overdose and withdrawal state in ITB therapy. Only original articles in English involving adult population were included. Initial search revealed 130 articles. After reading the abstract, 13 studies on ITB overdose and 23 studies on ITB withdrawal were deemed suitable for inclusion. All studies were either single-case studies or case series. Acute ITB overdose is managed with immediate cessation of baclofen delivery through the system, reducing the baclofen load by cerebrospinal fluid aspiration and by providing supportive treatment in an intensive care setting. There is no specific antidote for reversing overdose symptoms. Acute ITB withdrawal is managed by restoring the delivery of ITB, providing supportive care in an intensive care setting and using drugs like low dose propofol or benzodiazepines in selected cases. Early involvement of ITB physicians is strongly recommended.

  15. Imaging Sex Differences in Regional Brain Metabolism during Acute Opioid Withdrawal

    PubMed Central

    Santoro, Giovanni C; Carrion, Joseph; Dewey, Stephen L

    2017-01-01

    The rate of opioid overdose continues to rise, necessitating improved treatment options. Current therapeutic approaches rely on administration of either a blocking agent, such as naloxone, or chronic treatment with replacement drugs, including methadone and/or buprenorphine. Recent findings suggest that males and females respond to these treatments uniquely. In an effort to better understand this sex-specific variation in treatment efficacy, we investigated the effects of acute opioid withdrawal in male and female rats using 18FDG and microPET. These data demonstrate that acute opioid withdrawal produces metabolic alterations in brain regions associated with reward and drug dependence, namely corpus striatum, thalamic nuclei, septum, and frontal cortex. Furthermore, certain changes are unique to males. Specifically, males demonstrated increased metabolism in the anterior cingulate cortex and the ventral hippocampus (CA3) following acute opioid withdrawal. If males and females exhibit sex-specific changes in regional brain metabolism following acute opioid withdrawal, then perhaps it is not surprising that they respond to treatment differently. PMID:29046888

  16. Association of testosterone and BDNF serum levels with craving during alcohol withdrawal.

    PubMed

    Heberlein, Annemarie; Lenz, Bernd; Opfermann, Birgitt; Gröschl, Michael; Janke, Eva; Stange, Katrin; Groh, Adrian; Kornhuber, Johannes; Frieling, Helge; Bleich, Stefan; Hillemacher, Thomas

    2016-08-01

    Preclinical and clinical studies show associations between testosterone and brain-derived neurotrophic growth factor (BDNF) serum levels. BDNF and testosterone have been independently reported to influence alcohol consumption. Therefore, we aimed to investigate a possible interplay of testosterone and BDNF contributing to alcohol dependence. Regarding possible interplay of testosterone and BDNF and the activity of the hypothalamic pituitary axis (HPA), we included cortisol serum levels in our research. We investigated testosterone and BDNF serum levels in a sample of 99 male alcohol-dependent patients during alcohol withdrawal (day 1, 7, and 14) and compared them to a healthy male control group (n = 17). The testosterone serum levels were significantly (p < 0.001) higher in the patients' group than in the control group and decreased significantly during alcohol withdrawal (p < 0.001). The decrease of testosterone serum levels during alcohol withdrawal (days 1-7) was significantly associated with the BDNF serum levels (day 1: p = 0.008). In a subgroup of patients showing high cortisol serum levels (putatively mirroring high HPA activity), we found a significant association of BDNF and testosterone as well as with alcohol craving measured by the Obsessive and Compulsive Drinking Scale (OCDS). Our data suggest a possible association of BDNF and testosterone serum levels, which may be relevant for the symptomatology of alcohol dependence. Further studies are needed to clarify our results. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. INFANT EMOTIONAL WITHDRAWAL: A PRECURSOR OF AFFECTIVE AND COGNITIVE DISTURBANCE IN FETAL ALCOHOL SPECTRUM DISORDERS

    PubMed Central

    Molteno, Christopher D.; Jacobson, Joseph L.; Carter, R. Colin; Dodge, Neil C.; Jacobson, Sandra W.

    2013-01-01

    Objectives To test the hypothesis that emotional withdrawal is an early indicator of affective disorder in infants heavily exposed prenatally to alcohol, which is independent of alcohol-related effects on mother-infant interaction and temperament and discriminated between children later diagnosed with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive and affective outcomes at 5 and 9 years. Methods The sample consisted of Cape Coloured (mixed ancestry) infants, whose mothers were interviewed during pregnancy regarding their alcohol consumption using a timeline follow-back approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video recordings during free play and infant feeding at 6.5 months (n = 127). Infant temperament was assessed by maternal report on the EAS Temperament Survey at 13 months (n = 119). Socio-demographic and psychological correlates of maternal alcohol use and infant iron deficiency were examined as potential confounders. The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years; cognitive and affective function, at 5 and 9 years. Results Prenatal alcohol exposure was associated with increased infant emotional withdrawal and decreased activity, but unrelated to mother-infant interaction or any other temperament measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more emotional withdrawal and less responsivity and activity as infants. Infant withdrawal, responsivity, quality of interaction, and maternal sensitivity also predicted poorer IQ and affective response at 5 and 9 years. When all four infant affective measures were examined simultaneously in a regression analysis, only infant emotional withdrawal persisted as a significant predictor of 9-year IQ. Conclusions This study is the first to document a direct effect of fetal alcohol exposure on emotional withdrawal in infancy

  18. [Comparison of Two Symptom-Triggered Treatments for Alcohol Withdrawal: HAES vs. SAB-P].

    PubMed

    Holzbach, R; Ihlow, C; Takla, T; Kemper, U; Naber, D

    2016-02-01

    For alcohol withdrawal during hospitalization, often a medication as means for withdrawal needs to be chosen. Modern, score-controlled processes that can be used by the nursing staff after instruction by physicians are frequently not used and even unknown in hospitals. One reason for this is that some of the scores require checking several criteria and are therefore more time-consuming and complicated than use of a fixed-dosage strategy. The SAB-P and HAES are short with only 6 items that can be checked by the nursing staff. Safety of the Hamburg Alcohol Withdrawal Scale (Hamburger Alkoholentzugs-Skala (HAES)) was analyzed retrospectively and prospectively with regard to score-controlled alcohol-withdrawal treatment after rating by the nurse staff (Scoregesteuerte Alkoholentzugsbehandlung nach Rating durch das Pflegepersonal (SAB-P)). Incidence of complications in patients treated with SAB-P and HAES was nearly similar with 1% start of delirium and 3% seizures (SAB-P) and 0.5 to 1.5% start of delirium and 0 to 0.5% seizures in the HAES group. With both scales it was possible to start medical treatment while still under falling alcohol levels (0.93 and 0.91%, respectively). Medication dosage was initially higher using the HAES, so that the time needed to monitor withdrawal symptoms could be reduced (3.8 vs. 3.1 days). Using a score-controlled strategy for alcohol withdrawal leads to a lower complication rate than found in literature. The structured procedure was helpful for the nursing staff as well as for the physicians. SAB-P as well as HAES made withdrawal for the patients more comfortable and led to fewer complaints. Because of rapid reaction and faster symptom reduction of HAES, there was less time necessary for monitoring. Simple handling, clomethiazol, oxazepam or diazepam as applicable medication and clear documentation are the advantages of HAES. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Algorithm Analysis of the DSM-5 Alcohol Withdrawal Symptom.

    PubMed

    Martin, Christopher S; Vergés, Alvaro; Langenbucher, James W; Littlefield, Andrew; Chung, Tammy; Clark, Duncan B; Sher, Kenneth J

    2018-06-01

    Alcohol withdrawal (AW) is an important clinical and diagnostic feature of alcohol dependence. AW has been found to predict a worsened course of illness in clinical samples, but in some community studies, AW endorsement rates are strikingly high, suggesting false-positive symptom assignments. Little research has examined the validity of the DSM-5 algorithm for AW, which requires either the presence of at least 2 of 8 subcriteria (i.e., autonomic hyperactivity, tremulousness, insomnia, nausea, hallucinations, psychomotor agitation, anxiety, and grand mal seizures), or, the use of alcohol to avoid or relieve these symptoms. We used item and algorithm analyses of data from waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (current drinkers, n = 26,946 at wave 1) to study the validity of DSM-5 AW as operationalized by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV (AUDADIS-IV). A substantial proportion of individuals given the AW symptom reported only modest to moderate levels of alcohol use and alcohol problems. Alternative AW algorithms were superior to DSM-5 in terms of levels of alcohol use and alcohol problem severity among those with AW, group difference effect sizes, and predictive validity at a 3-year follow-up. The superior alternative algorithms included those that excluded the nausea subcriterion; required withdrawal-related distress or impairment; increased the AW subcriteria threshold from 2 to 3 items; and required tremulousness for AW symptom assignment. The results indicate that the DSM-5 definition of AW, as assessed by the AUDADIS-IV, has low specificity. This shortcoming can be addressed by making the algorithm for symptom assignment more stringent. Copyright © 2018 by the Research Society on Alcoholism.

  20. Acute Alcohol Consumption, Alcohol Outlets, and Gun Suicide

    PubMed Central

    Branas, Charles C.; Richmond, Therese S.; Ten Have, Thomas R.; Wiebe, Douglas J.

    2014-01-01

    A case–control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed. PMID:21929327

  1. Acute alcohol consumption, alcohol outlets, and gun suicide.

    PubMed

    Branas, Charles C; Richmond, Therese S; Ten Have, Thomas R; Wiebe, Douglas J

    2011-01-01

    A case-control study of 149 intentionally self-inflicted gun injury cases (including completed gun suicides) and 302 population-based controls was conducted from 2003 to 2006 in a major US city. Two focal independent variables, acute alcohol consumption and alcohol outlet availability, were measured. Conditional logistic regression was adjusted for confounding variables. Gun suicide risk to individuals in areas of high alcohol outlet availability was less than the gun suicide risk they incurred from acute alcohol consumption, especially to excess. This corroborates prior work but also uncovers new information about the relationships between acute alcohol consumption, alcohol outlets, and gun suicide. Study limitations and implications are discussed.

  2. AST: A Simplified 3-item Tool for Managing Alcohol Withdrawal.

    PubMed

    Holzman, Samuel B; Rastegar, Darius A

    2016-01-01

    This study compared the Glasgow Modified Alcohol Withdrawal Scale (GMAWS) and a newly devised 3-item "Anxiety Sweats Tremor" Scale (AST) to the Revised Clinical Institute Withdrawal Assessment Scale (CIWA-Ar)-the standard of care for symptom-triggered management of alcohol withdrawal syndrome. Our study took place over 2 separate 1-week observational periods, and included 332 serial evaluations from 85 unique patients. All study participants were treated per hospital protocol based on CIWA-Ar, with supplemental scoring initially by GMAWS and later by AST in tandem. Internal consistency, interitem correlation, and operational characteristics were explored. Median CIWA-Ar score across both phases was 6 (range 0-13), with a median GMAWS score of 2 (range 0-5) and an AST score of 3 (range 0-7). The internal consistency of CIWA-Ar and GMAWS were both poor, with Cronbach alpha scores of 0.46 (n = 156) and 0.41 (n = 156), respectively. The internal consistency of the AST scale was significantly better, with a Cronbach alpha of 0.68 (n = 176). AST identified individuals with CIWA-Ar ≥8 with an area under the receiver-operating characteristic curve of 0.83 (95% confidence interval 0.77-0.89), compared with 0.81 (95% confidence interval 0.74-0.88) for GMAWS. An AST score of ≥3 (out of a possible 9) predicted CIWA-Ar ≥8, with a sensitivity of 93% and a specificity of 63%, whereas the GMAWS had a sensitivity and specificity of 100% and 12%, respectively, based on previously defined cut-offs. A simple 3-item scale demonstrated good internal consistency and reliably identified individuals experiencing significant alcohol withdrawal. This scale needs to be tested in other settings and among patients with a broader spectrum of withdrawal severity.

  3. Evaluation of an Alcohol Withdrawal Protocol and a Preprinted Order Set at a Tertiary Care Hospital

    PubMed Central

    Ng, Karen; Dahri, Karen; Chow, Ivy; Legal, Michael

    2011-01-01

    Background: Alcohol withdrawal protocols involving symptom-triggered administration of benzodiazepine have been established to reduce the duration of treatment and the cumulative benzodiazepine dose (relative to usual care). However, the effects of a protocol combining fixed-schedule and symptom-triggered benzodiazepine dosing are less clear. Objective: To assess the efficacy and safety of a combination fixed-scheduled and symptom-triggered benzodiazepine dosing protocol for alcohol withdrawal, relative to usual care, for medical inpatients at a tertiary care hospital. Methods: A chart review of admissions to the internal medicine service for alcohol withdrawal was conducted to compare treatment outcomes before (October 2005 to April 2007) and after (October 2007 to April 2009) implementation of the combination protocol. The primary outcome was duration of benzodiazepine treatment for alcohol withdrawal. The secondary outcomes were cumulative benzodiazepine dose administered, safety implications, and use of adjunctive medications. Results: A total of 159 patients met the inclusion criteria. Assessable data were available for 71 charts from the pre-implementation period and 72 charts from the post-implementation period. The median duration of benzodiazepine treatment was 91 h before implementation and 57 h after implementation (p < 0.001). Use of the protocol was also associated with a significant reduction in severe complications of alcohol withdrawal (50% versus 33%, p = 0.019), median cumulative benzodiazepine dose (in lorazepam equivalents) (20.0 mg versus 15.5 mg, p = 0.026), and use of adjunctive medications (65% versus 38%, p = 0.001). The incidence of serious adverse outcomes of treatment with benzodiazepines was not significantly different between the 2 groups. Conclusions: Implementation of an alcohol withdrawal protocol with a combination of fixed-schedule and symptom-triggered benzodiazepine dosing in a medical ward was associated with a shorter duration

  4. Neurologic complications of alcoholism.

    PubMed

    Noble, James M; Weimer, Louis H

    2014-06-01

    This review serves as an overview of neurologic conditions associated with alcohol abuse or withdrawal, including epidemiology, clinical symptoms, diagnostic approach, and treatment. Frequent alcohol abuse and frank alcoholism are very common among adults in the United States. Although rates decline with each decade, as many as 10% of the elderly drink excessively. Given the ubiquitous nature of alcoholism in society, its complications have been clinically recognized for generations, with recent advances focusing on improved understanding of ethanol's biochemical targets and the pathophysiology of its complications. The chronic effects of alcohol abuse are myriad and include neurologic complications through both direct and indirect effects on the central and peripheral nervous systems. These disorders include several encephalopathic states related to alcohol intoxication, withdrawal, and related nutritional deficiencies; acute and chronic toxic and nutritional peripheral neuropathies; and myopathy. Although prevention of alcoholism and its neurologic complications is the optimal strategy, this article reviews the specific treatment algorithms for alcohol withdrawal and its related nutritional deficiency states.

  5. Distinct effects of protracted withdrawal on affect, craving, selective attention and executive functions among alcohol-dependent patients.

    PubMed

    Cordovil De Sousa Uva, Mariana; Luminet, Olivier; Cortesi, Marie; Constant, Eric; Derely, Marc; De Timary, Philippe

    2010-01-01

    The present study examined the effects of protracted alcohol withdrawal on affectivity, craving, selective attention and executive functions (EFs) in alcohol-dependent patients. Selective attention (The D2 Cancellation Test), flexibility (Trail Making Test), inhibition (Stroop Task), decision making (Iowa Gambling Task), craving (Obsessive-Compulsive Drinking Scale) and state affectivity (Positive and Negative Affectivity Schedule) were assessed in alcohol-dependent patients (DSM-IV, n = 35) matched to non-alcohol-dependent participants (n = 22) at the onset (T1: day 1 or 2) and at the end (T2: days 14-18) of protracted withdrawal during rehab. Alcohol-dependent patients' abilities to focus their attention on relevant information, to switch from one pattern to another, to inhibit irrelevant information and to make advantageous choices were lower than those of control participants during both times of a withdrawal cure. No effect of time emerged from analyses for selective attention and EF deficits. Conversely, significant differences between T1 and T2 were observed for craving and affect scores indicating a weakening of alcohol craving and negative affect as well as an improvement of positive affect among patients from onset to the end of cure. Control functions of the Supervisory Attentional System (Norman and Shallice, 1986) were impaired and did not improve during a 3-week withdrawal cure, whereas alcohol craving and negative state affectivity significantly improved in parallel during this period. Implications for understanding the clinical processes of withdrawal are discussed.

  6. Behavioral and biochemical effects of ethanol withdrawal in zebrafish.

    PubMed

    da Silva Chaves, Suianny Nayara; Felício, Gabriel Rocha; Costa, Bruna Patrícia Dutra; de Oliveira, Witallo Etevaldo Araújo; Lima-Maximino, Monica Gomes; Siqueira Silva, Diógenes Henrique de; Maximino, Caio

    2018-06-01

    Chronic alcohol use induces adaptations and toxicity that can induce symptoms of anxiety, autonomic hyperarousal, and epileptic seizures when alcohol is removed (withdrawal syndrome). Zebrafish has recently gained wide attention as a behavioral model to study the neurobehavioral effects of acute and chronic alcohol use, including withdrawal. The literature, however, is very contradictory on findings regarding withdrawal effects, with some studies reporting increased anxiety, while others report no effect. A meta-analytic approach was taken to find the sources of this heterogeneity, and ethanol concentration during exposure and exposure duration were found to be the main sources of variation. A conceptual replication was also made using continuous exposure for 16 days in waterborne ethanol (0.5%) and assessing anxiety-like behavior in the light/dark test after 60 min withdrawal. Withdrawal was shown to reduce preference for darkness, consistent with decreased anxiety, but to increase risk assessment, consistent with increased anxiety. Animals were also subjected to the withdrawal protocol and injected with pilocarpine in a sub-convulsive dose to assess susceptibility to epileptic seizure-like behavior. The protocol was sufficient to increase susceptibility to epileptic seizure-like behavior in animals exposed to ethanol. Finally, withdrawal also decreased catalase activity in the brain, but not in the head kidney, suggesting mechanisms associated with the behavioral effects of ethanol withdrawal. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Suppression of hypothalamic-pituitary-adrenal axis by acute heroin challenge in rats during acute and chronic withdrawal from chronic heroin administration

    PubMed Central

    Zhou, Yan; Leri, Francesco; Ho, Ann; Kreek, Mary Jeanne

    2013-01-01

    It is known that heroin dependence and withdrawal are associated with changes in the hypothalamic-pituitary-adrenal (HPA) axis. The objective of these studies in rats was to systematically investigate the level of HPA activity and response to a heroin challenge at two time points during heroin withdrawal, and to characterize the expression of associated stress-related genes 30 minutes after each heroin challenge. Rats received chronic (10-day) intermittent escalating-dose heroin administration (3×2.5 mg/kg/day on day 1; 3×20 mg/kg/day by day 10). Hormonal and neurochemical assessments were performed in acute (12 hours after last heroin injection) and chronic (10 days after the last injection) withdrawal. Both plasma ACTH and corticosterone levels were elevated during acute withdrawal, and heroin challenge at 20 mg/kg (the last dose of chronic escalation) at this time point attenuated this HPA hyperactivity. During chronic withdrawal, HPA hormonal levels returned to baseline, but heroin challenge at 5 mg/kg decreased ACTH levels. In contrast, this dose of heroin challenge stimulated the HPA axis in heroin naïve rats. In the anterior pituitary, pro-opiomelanocortin (POMC) mRNA levels were increased during acute withdrawal and retuned to control levels after chronic withdrawal. In the medial hypothalamus, however, the POMC mRNA levels were decreased during acute withdrawal, and increased after chronic withdrawal. Our results suggest a long-lasting change in HPA abnormal responsivity during chronic heroin withdrawal. PMID:23771528

  8. Modulation of ethanol withdrawal-induced anxiety-like behavior during later withdrawals by treatment of early withdrawals with benzodiazepine/gamma-aminobutyric acid ligands.

    PubMed

    Knapp, Darin J; Overstreet, David H; Breese, George R

    2005-04-01

    Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal-associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of gamma-aminobutyric acid-modulating drugs on social interaction behavior-an established model of anxiety-in rats exposed to repeated cycles of ethanol treatment and withdrawal. Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl-6, 7-dymerhoxy-4-ethyl-beta-carboline-3-carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Single-dose administration of drugs that enhance or diminish activity at benzodiazepine-gamma-aminobutyric acid- receptors during earlier withdrawals

  9. Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

    PubMed

    Richter, Christoph; Hinzpeter, Axel; Schmidt, Folkhard; Kienast, Thorsten; Preuss, Ulrich W; Plenge, Thomas; Heinz, Andreas; Schaefer, Martin

    2010-12-01

    Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

  10. Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake.

    PubMed

    Nobre, Manoel Jorge

    2016-12-01

    Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

  11. Involvement of delta opioid receptors in alcohol withdrawal-induced mechanical allodynia in male C57BL/6 mice.

    PubMed

    Alongkronrusmee, Doungkamol; Chiang, Terrance; van Rijn, Richard M

    2016-10-01

    As a legal drug, alcohol is commonly abused and it is estimated that 17 million adults in the United States suffer from alcohol use disorder. Heavy alcoholics can experience withdrawal symptoms including anxiety and mechanical allodynia that can facilitate relapse. The molecular mechanisms underlying this phenomenon are not well understood, which stifles development of new therapeutics. Here we investigate whether delta opioid receptors (DORs) play an active role in alcohol withdrawal-induced mechanical allodynia (AWiMA) and if DOR agonists may provide analgesic relief from AWiMA. To study AWiMA, adult male wild-type and DOR knockout C57BL/6 mice were exposed to alcohol by a voluntary drinking model or oral gavage exposure model, which we developed and validated here. We also used the DOR-selective agonist TAN-67 and antagonist naltrindole to examine the involvement of DORs in AWiMA, which was measured using a von Frey model of mechanical allodynia. We created a robust model of alcohol withdrawal-induced anxiety and mechanical allodynia by orally gavaging mice with 3g/kg alcohol for three weeks. AWiMA was exacerbated and prolonged in DOR knockout mice as well as by pharmacological blockade of DORs compared to control mice. However, analgesia induced by TAN-67 was attenuated during withdrawal in alcohol-gavaged mice. DORs appear to play a protective role in the establishment of AWiMA. Our current results indicate that DORs could be targeted to prevent or reduce the development of AWiMA during alcohol use; however, DORs may be a less suitable target to treat AWiMA during active withdrawal. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Anxiety level and correlates in methamphetamine-dependent patients during acute withdrawal.

    PubMed

    Su, Hang; Zhang, Jie; Ren, Wenwei; Xie, Ying; Tao, Jingyan; Zhang, Xiangyang; He, Jincai

    2017-04-01

    Anxiety is often a core element of withdrawal symptoms; however, risk factors associated with anxiety symptoms during the early stage of withdrawal in methamphetamine (METH) users are not well understood. Two hundred ten METH-dependent subjects who had been abstinent for 1 to 7 days were recruited. We used a set of self-administrative questionnaires eliciting information on sociodemographics, detailed drug use history and anxiety. Beck Anxiety Inventory (BAI) was used to measure anxiety symptoms. METH users had a mean BAI score of 6.9; 72 (34.3%) of the study sample had anxiety symptoms during acute METH withdrawal, including 42 (20.0%) with mild anxiety, 25 (11.9%) with moderate anxiety, and 5 (2.4%) with severe anxiety. In addition, gender (female), higher frequency of drug use, and history of polysubstance use were significantly correlated with anxiety symptoms during acute METH withdrawal. Anxiety symptoms appear to be common during the first week of METH abstinence, and several risk factors are identified.

  13. Physical dependence on nitrous oxide in mice: resemblance to alcohol but not to opiate withdrawal.

    PubMed

    Milne, B; Cervenko, F W; Jhamandas, K H

    1981-01-01

    Mice of two strains, Crl:CD-1(1CR)Br and C57BL6, were exposed to nitrous oxide at concentrations of 50, 65 and 80 per cent for 34 or 68 hours. Cessation of nitrous oxide resulted in characteristic convulsions similar to those seen in alcohol withdrawal in all mice. These peaked in severity within 2-3 minutes after removal from nitrous oxide and declined over 6 hours. The severity and duration of these convulsions were related to the nitrous oxide concentration and duration of exposure. Naloxone or naltrexone produced no significant increase in severity of convulsions. The narcotic antagonists did not precipitate acute weight loss or characteristic jumping behaviour seen in animals dependent on opiates. These results demonstrate that chronic exposure to nitrous oxide results in development of physical dependence which resembles alcohol and not opiate dependence. Analgesia and physical dependence produced by nitrous oxide appear to be mediated through separate mechanisms.

  14. Ethosuximide reduces electrographical and behavioral correlates of alcohol withdrawal seizure in DBA/2J mice

    PubMed Central

    Riegle, Melissa A.; Masicampo, Melissa M.; Caulder, Erin H.; Godwin, Dwayne W.

    2015-01-01

    Chronic alcohol abuse depresses the nervous system and, upon cessation, rebound hyperexcitability can result in withdrawal seizure. Withdrawal symptoms, including seizures, may drive individuals to relapse, thus representing a significant barrier to recovery. Our lab previously identified an upregulation of the thalamic T-type calcium (T channel) isoform CaV3.2 as a potential contributor to the generation and propagation of seizures in a model of withdrawal. In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity. DBA/2J mice were exposed to an intermittent ethanol exposure paradigm. Mice were treated with saline or ETX in each withdrawal period, and cortical EEG activity was recorded to determine seizure severity. We observed a progression in seizure activity with each successive withdrawal period. Treatment with ETX reduced ethanol withdrawal-induced spike and wave discharges (SWDs), in terms of absolute number, duration of events, and contribution to EEG power reduction in the 6–10 Hz frequency range. We also evaluated the effects of ETX on handling-induced convulsions. Overall, we observed a decrease in handling-induced convulsion severity in mice treated with ETX. Our findings suggest that ETX may be a useful pharmacological agent for studies of alcohol withdrawal and treatment of resulting seizures. PMID:24933286

  15. Psychosocial withdrawal characteristics of nicotine compared with alcohol and caffeine.

    PubMed

    Miyata, Hisatsugu; Hironaka, Naoyuki; Takada, Kohji; Miyasato, Katsumasa; Nakamura, Koichi; Yanagita, Tomoji

    2008-10-01

    The purpose of the present study was to observe the psychosocial characteristics of withdrawal from cigarette smoking in comparison with those from caffeine (CAF) and alcoholic (ALC) beverage withdrawal. Twenty-seven healthy volunteers at a medial level of dependence on both cigarettes (nicotine, NCT) and either CAF or ALC, as judged by the DSM-IV-TR criteria for substance dependence, participated in this study. The participants were required to abstain from smoking and either CAF or ALC for 7 days, each one after another, with a 7-day interval. The order of abstinence was counterbalanced among the participants. Psychosocial parameters, including a desire for substances, social activity function, well-being, withdrawal symptoms, and vital signs, were assessed during the withdrawal periods. The study protocol was approved by the Jikei University Review Board. The results indicated that there were no differences in the maximum level of desire for a substance and the influence on social activity function between NCT and other substances during the withdrawal periods. As for withdrawal symptoms, NCT caused a more intensive degree of irritability than CAF or ALC, and a more intensive degree of difficulty concentrating and restlessness than did withdrawal from ALC. However, the subjective well-being questionnaire indicated no differences in these symptoms between NCT and other substances. The present results suggest that there are no significant differences in psychosocial manifestations regarding the difficulty in abstaining from NCT, CAF, and ALC.

  16. Symptom-Triggered vs. Fixed-Dosing Management of Alcohol Withdrawal Syndrome.

    PubMed

    Skinner, Reagan T

    2014-01-01

    A literature review was conducted with the objective of creating evidence-based recommendations for use of symptom-triggered therapy (STT) or fixed-schedule dosing in treating alcohol withdrawal syndrome in inpatients. Use of STT reduced duration of therapy as well as the number of patients requiring treatment or medication, potentially reducing costs and risk of adverse medication reactions.

  17. Evaluation of the appropriate use of a CIWA-Ar alcohol withdrawal protocol in the general hospital setting.

    PubMed

    Eloma, Amanda S; Tucciarone, Jason M; Hayes, Edmund M; Bronson, Brian D

    2018-01-01

    The Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) is an assessment tool used to quantify alcohol withdrawal syndrome (AWS) severity and inform benzodiazepine treatment for alcohol withdrawal. To evaluate the prescribing patterns and appropriate use of the CIWA-Ar protocol in a general hospital setting, as determined by the presence or absence of documented AWS risk factors, patients' ability to communicate, and provider awareness of the CIWA-Ar order. This retrospective chart review included 118 encounters of hospitalized patients placed on a CIWA-Ar protocol during one year. The following data were collected for each encounter: patient demographics, admitting diagnosis, ability to communicate, and admission blood alcohol level; and medical specialty of the clinician ordering CIWA-Ar, documentation of the presence or absence of established AWS risk factors, specific parameters of the protocol ordered, service admitted to, provider documentation of awareness of the active protocol within 48 h of initial order, total benzodiazepine dose equivalents administered and associated adverse events. 57% of patients who started on a CIWA-Ar protocol had either zero or one documented risk factor for AWS (19% and 38% respectively). 20% had no documentation of recent alcohol use. 14% were unable to communicate. 19% of medical records lacked documentation of provider awareness of the ordered protocol. Benzodiazepine associated adverse events were documented in 15% of encounters. The judicious use of CIWA-Ar protocols in general hospitals requires mechanisms to ensure assessment of validated alcohol withdrawal risk factors, exclusion of patients who cannot communicate, and continuity of care during transitions.

  18. The craving withdrawal model for alcoholism: towards the DSM-V. Improving the discriminant validity of alcohol use disorder diagnosis.

    PubMed

    de Bruijn, Carla; van den Brink, Wim; de Graaf, Ron; Vollebergh, Wilma A M

    2005-01-01

    To compare the discriminant validity of the DSM-IV and the ICD-10 classification of alcohol use disorders (AUD) with an alternative classification, the craving withdrawal model (CWM). CWM requires craving and withdrawal for the diagnosis of alcohol dependence and raises the alcohol abuse threshold to two DSM-IV AUD criteria. Data were derived from The Netherlands Mental Health Survey and Incidence Study, a large representative sample of the general Dutch population. In the present study, only non-abstinent subjects were included (n=6041). Three diagnostic systems (DSM-IV, ICD-10, and CWM) were compared using the following discriminant variables: alcohol intake, psychiatric comorbidity, functional status, familial alcohol problems, and treatment sought. The year prevalence of CWM alcohol dependence was lower than the prevalence of ICD-10 and DSM-IV dependence (0.3% vs 1.4% and 1.4%). The year prevalence of abuse was similar for CWM and DSM-IV (4.7 and 4.9%), but lower for ICD-10 harmful use (1.7%). DSM-IV resulted in a poor distinction between normality and abuse and ICD-10 resulted in a poor distinction between harmful use and dependence. In contrast, the CWM distinctions between normality and abuse, and between abuse, and dependence were significant for most of the discriminant variables. This study indicates that CWM improves the discriminant validity of AUD diagnoses. The predictive validity of the CWM for alcohol and other substance use disorders remain to be studied.

  19. Sex Differences in Acute Ethanol Withdrawal Severity After Adrenalectomy and Gonadectomy in WSP and WSR Mice

    PubMed Central

    Strong, Moriah N.; Kaufman, Katherine R.; Crabbe, John C.; Finn, Deborah A.

    2009-01-01

    Recent findings suggest that the ability of ethanol (EtOH) to increase the levels of neurosteroids with potent γ-aminobutyric acid (GABA)ergic properties can influence measures of EtOH sensitivity. Earlier studies determined that removal of the adrenals and gonads diminished the steroidogenic effect of EtOH and significantly increased acute EtOH withdrawal severity in two inbred mouse strains that differed in withdrawal severity, suggesting the contribution of anticonvulsant GABAergic steroids to acute withdrawal in intact animals. Thus, the goal of the present studies was to investigate the consequence of steroid removal on acute EtOH withdrawal through excision of the adrenals and gonads, in another genetic animal model of EtOH withdrawal differences, the Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) selected lines. Male and female WSP and WSR mice underwent surgical removal of the adrenals and gonads or no organ removal (SHAM). One to two weeks later, baseline handling-induced convulsions (HICs) were assessed, mice were given a 4 g/kg dose of ethanol, and HICs were measured hourly for 12 hours and then at 24 hours. The combination surgery significantly increased EtOH withdrawal in WSP and WSR female mice, as measured by area under the curve (AUC) and peak HIC scores. AUC was significantly positively correlated with plasma corticosterone levels and significantly negatively correlated with progesterone levels. In contrast, surgical status did not alter withdrawal severity in male WSP and WSR mice. Overall, the increase in acute ethanol withdrawal severity in female WSP and WSR mice following adrenalectomy and gonadectomy corroborate our recent evidence that withdrawal from a high dose of EtOH can be modulated by anticonvulsant steroids produced in the periphery. PMID:19671463

  20. Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure.

    PubMed

    Dominguez, G; Dagnas, M; Decorte, L; Vandesquille, M; Belzung, C; Béracochéa, D; Mons, N

    2016-03-01

    Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.

  1. Sex Differences in the Effect of Finasteride on Acute Ethanol Withdrawal Severity in C57BL/6J and DBA/2J Mice

    PubMed Central

    Gorin-Meyer, Rebecca E.; Wiren, Kristine M.; Tanchuck, Michelle A.; Long, Season L.; Yoneyama, Naomi; Finn, Deborah A.

    2007-01-01

    The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of γ-aminobutyric acidA (GABAA) receptors that can modulate ethanol (EtOH) withdrawal. The 5α-reductase inhibitor finasteride can block the formation of ALLO and other GABAergic neurosteroids and also reduce certain effects of EtOH. Treatment with finasteride during chronic EtOH exposure decreased EtOH withdrawal severity and blood EtOH concentrations (BECs), suggesting an additional effect of finasteride on EtOH pharmacokinetics. Thus, the purpose of the present study was to determine the effect of finasteride on acute EtOH withdrawal severity, to minimize the effect of finasteride on EtOH metabolism. Male and female C57BL/6J and DBA/2J mice received a pretreatment of finasteride (50 mg/kg i.p.) or vehicle 24 hours prior to an injection of EtOH (4 g/kg i.p.) or saline. Handling-induced convulsions (HICs) were scored at baseline, and then over a 24 hr period after EtOH or saline injection. In another experiment, plasma estradiol and corticosterone levels were assessed at selected time points (0, 2, 8, and 24 hrs). In a final study, retro-orbital blood samples were collected at 30, 60, 120, and 240 minutes post-EtOH administration to access finasteride’s effects on EtOH clearance parameters. Pretreatment with finasteride increased acute EtOH withdrawal severity in female C57BL/6J and DBA/2J mice but decreased withdrawal severity in male mice of both strains. Finasteride did not alter BECs, EtOH clearance, estradiol, or corticosterone concentrations in a manner that appeared to contribute to the sex difference in finasteride’s effect on acute EtOH withdrawal severity. These findings suggest that male and female C57BL/6J and DBA/2J mice differ in their sensitivity to changes in ALLO or other GABAergic neurosteroid levels during acute EtOH withdrawal. Sex differences in the modulation of GABAergic 5α-reduced steroids may be an important consideration in understanding and developing

  2. Comparison of enteral ethanol and benzodiazepines for alcohol withdrawal in neurocritical care patients.

    PubMed

    Gipson, Gregory; Tran, Kim; Hoang, Cuong; Treggiari, Miriam

    2016-09-01

    We designed a study to evaluate the use of benzodiazepines and ethanol in patients being assessed for alcohol withdrawal and compare outcomes between the two agents. This is a retrospective chart review of patients admitted to neurocritical care or neurosurgical services who were at risk for ethanol withdrawal between June 2011 and September 2015. Patients were divided into two groups based on the first medication administered for alcohol withdrawal management, either benzodiazepine (n=50) or enteral ethanol (n=50). The primary endpoint was the maximum change in Clinical Institute Withdrawal Assessment of Alcohol scale (CIWA) score within the first 24hours. Secondary endpoints included maximum and minimum CIWA score in 5days, length of stay, and change in Glasgow Coma Scale. Study groups differed by mortality risk, level of coma at admission, and other clinical characteristics, with the ethanol group appearing less severely ill. There was no significant difference between the two groups in the maximum change in CIWA score at 24hours (-0.97, 95%CI: -3.21 to 1.27, p=0.39). Hospital and intensive care unit length of stay was 6.5 days and 1 day shorter for the ethanol group (p=0.03 and p=0.02, respectively). In summary, enteral ethanol was preferentially used in patients who are more likely to be capable of tolerating oral intake. We found that the change from baseline in CIWA score or other physiologic variables was not substantially different between the two agents. The overall utility of benzodiazepines and enteral ethanol remains unclear for this population and further study is needed to determine superiority. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N(G)-nitro-L-arginine methyl ester and L-arginine.

    PubMed

    Boban-Blagaic, Alenka; Blagaic, Vladimir; Romic, Zeljko; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Seiwerth, Sven; Sikiric, Predrag

    2006-01-01

    Alcohol disturbances, NO stimulation (by the NO-precursor L-arginine), and/or NO-synthesis blockade (by N(G)-nitro-L-arginine methyl ester, i.e. L-NAME) were challenged with stable gastric pentadecapeptide BPC 157, which inhibits both acute alcohol intoxication and alcohol withdrawal symptoms. Mice received intraperitoneally (i.p.) BPC 157 (10 microg/kg), L-NAME (10 mg/kg), and L-arginine (400 mg/kg), alone or in combination, 5 minutes before or after acute ethanol (4 g/kg i.p.) intoxication or after 0, 3, or 7 hours of withdrawal after drinking 20% alcohol for 13 days. BPC 157 rapidly opposes the strongest disturbance presentations in acute intoxication (sustained ethanol anesthesia, complete loss of righting reflex, no reaction to external stimuli, hypothermia, 25% mortality) and withdrawal (prominent seizures). NO-agents: Aggravation of acute alcohol intoxication and opposition to withdrawal are common, but the later intervals affected by L-arginine and the action throughout the experiment by L-NAME are distinctive. Given together, L-arginine and L-NAME counteract each other, while either the "L-NAME presentation" (acute intoxication) or the "L-arginine presentation" (withdrawal) predominates. BPC157+NO-agent: In acute intoxication (L-NAME predominating in NO-system functioning to aggravate intoxication), both BPC157+L-NAME and BPC157+L-arginine follow the presentation of L-NAME, but without worsened mortality. In withdrawal (L-arginine predominating in NO-system functioning to oppose disturbance symptoms), BPC157+L-NAME follows the presentation of L-NAME, while BPC 157+L-arginine imitates that of L-arginine. The relationships among pentadecapeptide BPC 157, the NO-system, acute alcohol intoxication, and opposed withdrawal may be important, presenting pentadecapeptide BPC 157 as a suitable alcohol antagonist.

  4. Management of precipitated opiate withdrawal syndrome induced by nalmefene mistakenly prescribed in opiate-dependent patients: a review for clinicians.

    PubMed

    Franchitto, Nicolas; Jullian, Benedicte; Salles, Juliette; Pelissier, Fanny; Rolland, Benjamin

    2017-06-01

    Nalmefene, a long-acting µ-opioid antagonist approved to treat alcohol use disorder, is occasionally mistakenly prescribed to opiate-dependent or opioid-treated patients. We review recent literature on drug-drug interactions between nalmefene and opioids that lead to precipitated opioid withdrawal, and focus on its management and planning for care at discharge. Areas covered: This article provides a brief and comprehensive review of management of precipitated opioid withdrawal syndrome when nalmefene is associated with an opioid, whether misused or legally prescribed. Expert opinion: When treating an opiate-dependent patient with co-occurring alcohol use disorder, both conditions need to be a focus of clinical attention. New drugs for alcohol use disorder have been approved, but must be given cautiously and with a full understanding of their potential drug-drug interactions with opioid medications. Opiate-dependent patients should be intensively monitored for risk factors of alcohol use disorder and should be continuously motivated for treatment maintenance. When nalmefene is administered to opiate-dependent patients, acute opioid withdrawal syndrome may occur. Management of precipitated acute opioid withdrawal may include short or long-acting µ-opioid agonists during hospitalization, in addition to supportive treatment. The best management of polydrug abusers is based on a multidisciplinary approach, which should be pursued and improved through continuing medical education.

  5. Preliminary effects of progressive muscle relaxation on cigarette craving and withdrawal symptoms in experienced smokers in acute cigarette abstinence: a randomized controlled trial.

    PubMed

    Limsanon, Thatsanee; Kalayasiri, Rasmon

    2015-03-01

    Cigarette craving usually occurs in conjunction with unpleasant feelings, including stress, as part of a withdrawal syndrome. Progressive muscle relaxation (PMR), a behavioral technique used to reduce stress by concentrating on achieving muscle relaxation, may reduce levels of cigarette craving and other substance-related negative feelings and withdrawal symptoms. Demographic and cigarette use data were collected from 32 experienced smokers at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand using the Semi-Structured Assessment for Drug Dependence and Alcoholism. Participants were asked to refrain from smoking for at least 3 hours before the visit (acute abstinence) and were randomly allocated to a 1-session PMR group (n =16) or a control activity group (e.g., reading newspaper, n =16). The intervention group was instructed to practice PMR individually in a quiet, private, air-conditioned room for about 20minutes. Craving, other substance-related feelings, and autonomic nervous responses (e.g., blood pressure and pulse rate) were assessed immediately before and after the 1-session intervention. There were no differences in demographics, cigarette use/dependence, and baseline craving characteristics between the PMR and control groups. However, the control group had higher levels of high and paranoia feeling, and pulse rate than the PMR group at baseline. After practicing PMR, but not after a control activity, smokers undergoing acute abstinence had significantly lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than at baseline. After controlling for baseline differences, abstaining smokers using PMR had lower levels of cigarette craving, withdrawal symptoms, and systolic blood pressure than smokers who undertook a control activity. PMR significantly reduces cigarette craving, withdrawal symptoms, and blood pressure in smokers undergoing acute abstinence. PMR may be used as an adjunct to cigarette dependency treatments

  6. Strain-dependent Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    PubMed Central

    Portugal, George S.; Wilkinson, Derek S.; Kenney, Justin W.; Sullivan, Colleen

    2013-01-01

    The effects of nicotine on cognitive processes such as learning and memory may play an important role in the addictive liability of tobacco. However, it remains unknown whether genetic variability modulates the effects of nicotine on learning and memory. The present study characterized the effects of acute, chronic, and withdrawal from chronic nicotine administration on fear conditioning, somatic signs, and the elevated plus maze in 8 strains of inbred mice. Strain-dependent effects of acute nicotine and nicotine withdrawal on contextual fear conditioning, somatic signs, and the elevated plus maze were observed, but no association between the effects of acute nicotine and nicotine withdrawal on contextual fear conditioning were observed, suggesting that different genetic substrates may mediate these effects. The identification of genetic factors that may alter the effects of nicotine on cognition may lead to more efficacious treatments for nicotine addiction. PMID:21822688

  7. Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity.

    PubMed

    Roselli, Charles E; Finn, Timothy J; Ronnekleiv-Kelly, Sean M; Tanchuck, Michelle A; Kaufman, Katherine R; Finn, Deborah A

    2011-12-01

    Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. Published by Elsevier Inc.

  8. Localization of Brain 5α-Reductase Messenger RNA in Mice Selectively Bred for High Chronic Alcohol Withdrawal Severity

    PubMed Central

    Roselli, Charles E.; Finn, Tim J.; Ronnekleiv-Kelly, Sean M.; Tanchuck, Michelle A.; Kaufman, Katherine R.; Finn, Deborah A.

    2011-01-01

    Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone, WSP) and found that Srd5a1 was down-regulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72 h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity. PMID:21917407

  9. Dexmedetomidine in addition to benzodiazepine-based sedation in patients with alcohol withdrawal delirium.

    PubMed

    Tolonen, Jukka; Rossinen, Juhani; Alho, Hannu; Harjola, Veli-Pekka

    2013-12-01

    Alcohol withdrawal delirium (AWD) is often refractory to conventional medication. We report a prospective series of patients treated with α2-agonist dexmedetomidine added to conventional sedation. Eighteen patients with AWD were diagnosed by Confusion assessment method for ICU score. Treatment, complications, length of stay (LOS) in ICU and hospital were recorded. In addition, hospital and 1-year mortality were assessed. Dexmedetomidine was given for 23.9 (18.4) h [mean (SD)]. All the patients also received benzodiazepines but three patients were given haloperidole. No patient was intubated. The maximum infusion rate of dexmedetomidine was 1.5 (1.2) µg/kg/h. Time to resolution of AWD was 3.8 (1.3) days. The ICU LOS was 7.1 (2.7) days and in-hospital LOS 12.1 (4.5) days. No adverse events were observed although one patient died from acute pancreatitis. The use of dexmedetomidine in AWD seems safe but warrants further studies.

  10. Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis.

    PubMed

    Hunter, Jonathan Michael; Chan, Julian; Reid, Angeline Louise; Tan, Chistopher

    2013-01-25

    A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcohol-related liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms.

  11. Gamma-hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of relapses.

    PubMed

    Leone, Maurizio A; Vigna-Taglianti, Federica; Avanzi, Giancarlo; Brambilla, Romeo; Faggiano, Fabrizio

    2010-02-17

    Chronic excessive alcohol consumption may lead to dependence, and to alcohol withdrawal syndrome (AWS) in case of abrupt drinking cessation. Gamma-hydroxybutyric acid (GHB) can prevent and suppress withdrawal symptoms, and improve the medium-term abstinence rate. A clear balance between effectiveness and harmfulness has not been yet established. To evaluate the efficacy and safety of GHB for treatment of AWS and prevention of relapse We searched Cochrane Drugs and Alcohol Group' Register of Trials (October 2008), PubMed, EMBASE, CINAHL (January 2005 - October 2008), EconLIT (1969 to February 2008), reference list of retrieved articles Randomized controlled trials (RCTs) and Controlled Prospective Studies (CPS) evaluating the efficacy and the safety of GHB vs placebo or other pharmacological treatments. Three authors independently extracted data and assessed the methodological quality of studies. Thirteen RCTs were included. Eleven studies were conducted in Italy.For withdrawal syndrome, comparing GHB 50mg with placebo, results from 1 study, 23 participants favour GHB for withdrawal symptoms: WMD -12.1 (95% CI, -15.9 to -8.29) and side effects were more frequent in the placebo group: RR 16.2 (95% CI, 1.04 to 254.9).In the comparison with Chlormetiazole, for GHB 50mg, results from 1 study, 21 participants favour GHB for withdrawal symptoms: MD -3.40 (95% CI -5.09 to -1.71), for GHB 100mg, results from 1 study, 98 participants favour anticonvulsants for side effects: RR 1.84 (95% CI 1.19 to 2.85).At mid-term, comparing GHB with placebo, results favour GHB for abstinence rate (RR 5.35; 1.28-22.4), controlled drinking (RR 2.13; 1.07-5.54), relapses (RR 0.36; 0.21-0.63), and number of daily drinks (WMD -4.60; -6.18 to -3.02). GHB performed better than NTX and Disulfiram on abstinence (RR 2.59; 1.35-4.98, RR 1.66; 0.99-2.80 respectively). The association of GHB and NTX was better than NTX on abstinence (RR 12.2; 1.79-83.9), as well was the association of NTX, GHB and

  12. Prazosin + naltrexone decreases alcohol drinking more effectively than does either drug alone in P rats with a protracted history of extensive voluntary alcohol drinking, dependence and multiple withdrawals

    PubMed Central

    Rasmussen, Dennis D; Kincaid, Carrie L; Froehlich, Janice C

    2015-01-01

    Background Prazosin (PRZ, an α1-adrenergic receptor antagonist) and naltrexone (NTX, a non-specific opioid receptor antagonist) each decrease alcohol drinking when administered to rats selectively-bred for high voluntary alcohol drinking (alcohol-preferring, or “P”), and the combination of PRZ+NTX decreases alcohol drinking more effectively than does either drug alone. Since drug responsiveness can depend on history of alcohol drinking and dependence, we investigated whether various schedules of PRZ and NTX administration, alone or in combination, are effective in decreasing alcohol drinking in male P rats with a history of protracted voluntary alcohol drinking, dependence and repeated withdrawals closely resembling human alcoholism. Methods Male P rats became alcohol-dependent during 1 year of ad libitum 24 h/day access to food, water and 20% alcohol with repetitive temporary alcohol withdrawals. Four sequential studies then addressed effects of oral PRZ (2 mg/kg) and NTX (10 mg/kg), alone or together, on alcohol drinking during: 1) daily alcohol access with daily drug treatment, 2) intermittent alcohol access with daily drug treatment, 3) intermittent alcohol access with occasional drug treatment, and 4) post-deprivation reinstatement of alcohol access. Results The combination of PRZ+NTX consistently suppressed alcohol drinking during daily or intermittent alcohol access conditions and when drug treatment was either daily or occasional. PRZ+NTX was consistently more effective than either drug alone. The reduction in alcohol drinking was not due to sedation, motor effects or malaise. Conclusions Both daily and “as-needed” treatment with PRZ+NTX are highly effective in suppressing daily, intermittent and post-deprivation alcohol drinking in male P rats with a protracted history of alcohol dependence and repeated withdrawals. This drug combination may be especially effective for treating individuals with long histories of heavy alcohol abuse, dependence and

  13. Acute Legionella pneumophila infection masquerading as acute alcoholic hepatitis

    PubMed Central

    Hunter, Jonathan Michael; Chan, Julian; Reid, Angeline Louise; Tan, Chistopher

    2013-01-01

    A middle-aged man had deteriorated rapidly in hospital after being misdiagnosed with acute alcoholic hepatitis. Acute Legionnaires disease (Legionellosis) was subsequently diagnosed on rapid antigen urinary testing and further confirmed serologically. This led to appropriate antibiotic treatment and complete clinical resolution. Physicians caring for patients with alcohol-related liver disease should consider Legionella pneumophila in their differential diagnosis even with a paucity of respiratory symptoms. PMID:23355576

  14. Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

    PubMed

    Greenberg, G D; Huang, L C; Spence, S E; Schlumbohm, J P; Metten, P; Ozburn, A R; Crabbe, J C

    2016-04-01

    Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice. Published by Elsevier B.V.

  15. A dose for the wiser is enough: the alcohol benefits for associative learning in zebrafish.

    PubMed

    Chacon, Diana M; Luchiari, Ana C

    2014-08-04

    This study aimed to test seeking behavior caused by alcohol and the drug effects on learning in the zebrafish, Danio rerio. Three treatments were conducted: acute, chronic and withdrawal, using 0.10%, 0.25%, and 1.00% alcohol and control (0.00%) (vol/vol.%). For the drug seeking behavior, we used a place preference paradigm (shuttle box tank) before and after alcohol exposure in acute (single exposure) and chronic (7 days) treatments. We observed a change in the basal preference due to the association with alcohol only for 0.25% and 1.00% doses in both acute and chronic offering, indicating an alcohol-seeking behavior after the drug exposure. For the learning task, two treatments were tested: chronic alcohol exposure (26 days including the learning period) and alcohol withdrawal (15 days of alcohol exposure before the learning period). During the learning period, fish received light stimulus followed by food in a pre-defined area of the tank for 8 consecutive days. The low dose group (0.10%) learned the task by the 3rd day both in chronic and withdrawal treatments. The higher doses (0.25% and 1.00%) caused a learning impairment in the chronic treatment group, while fish from the alcohol withdrawal treatment displayed learning on the final testing day. Therefore, we suggest that high alcohol doses impair learning and cause drug seeking behavior, even after drug exposure cessation, while low doses positively affect learning and do not cause seeking behavior. Given our results we propose that the zebrafish is a promising model for identifying active compounds, antibodies or genes which modulate the alcohol dual effects: learning improvement and reinforcing behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Alcohol Withdrawal-Induced Seizure Susceptibility is Associated with an Upregulation of CaV1.3 Channels in the Rat Inferior Colliculus

    PubMed Central

    Akinfiresoye, Luli R.; Allard, Joanne S.; Lovinger, David M.

    2015-01-01

    Background: We previously reported increased current density through L-type voltage-gated Ca2+ (CaV1) channels in inferior colliculus (IC) neurons during alcohol withdrawal. However, the molecular correlate of this increased CaV1 current is currently unknown. Methods: Rats received three daily doses of ethanol every 8 hours for 4 consecutive days; control rats received vehicle. The IC was dissected at various time intervals following alcohol withdrawal, and the mRNA and protein levels of the CaV1.3 and CaV1.2 α1 subunits were measured. In separate experiments, rats were tested for their susceptibility to alcohol withdrawal–induced seizures (AWS) 3, 24, and 48 hours after alcohol withdrawal. Results: In the alcohol-treated group, AWS were observed 24 hours after withdrawal; no seizures were observed at 3 or 48 hours. No seizures were observed at any time in the control-treated rats. Compared to control-treated rats, the mRNA level of the CaV1.3 α1 subunit was increased 1.4-fold, 1.9-fold, and 1.3-fold at 3, 24, and 48 hours, respectively. In contrast, the mRNA level of the CaV1.2 α1 subunit increased 1.5-fold and 1.4-fold at 24 and 48 hours, respectively. At 24 hours, Western blot analyses revealed that the levels of the CaV1.3 and CaV1.2 α1 subunits increased by 52% and 32%, respectively, 24 hours after alcohol withdrawal. In contrast, the CaV1.2 and CaV1.3 α1 subunits were not altered at either 3 or 48 hours during alcohol withdrawal. Conclusions: Expression of the CaV1.3 α1 subunit increased in parallel with AWS development, suggesting that altered L-type CaV1.3 channel expression is an important feature of AWS pathogenesis. PMID:25556199

  17. Modulation of Ethanol Withdrawal–Induced Anxiety-Like Behavior During Later Withdrawals by Treatment of Early Withdrawals With Benzodiazepine/γ-Aminobutyric Acid Ligands

    PubMed Central

    Knapp, Darin J.; Overstreet, David H.; Breese, George R.

    2010-01-01

    Background Anxiety states, including those arising during acute or protracted withdrawal periods, may be precipitating factors in alcoholic relapse. Given the cyclical nature of ethanol withdrawal associated with repeated cycles of ethanol intake and abstinence in a pattern that often spans years, meaningful attempts to model ethanol withdrawal–associated anxiety should incorporate cycled ethanol treatments. The studies reported herein examined the effects of γ-aminobutyric acid–modulating drugs on social interaction behavior—an established model of anxiety—in rats exposed to repeated cycles of ethanol treatment and withdrawal. Methods Rats were exposed to 8 to 12 g/kg/day ethanol during three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). Ethanol was administered either at hour 4 of withdrawal after cessation of each of the first 2 ethanol cycles or during the final withdrawal only. In other groups, the early withdrawals were treated with alphaxalone, diazepam, PK11159, or flumazenil to block anxiety-like behavior during an untreated later (third) withdrawal. The benzodiazepine inverse agonist DMCM (methyl–6, 7–dymerhoxy–4–ethyl–beta–carboline–3–carboxylate) was also given repeatedly to determine whether it would sensitize anxiety-like behavior during a future withdrawal. Finally, the effects of all drugs on deficits in locomotor behavior were assessed. Results Pretreatment of earlier withdrawals with alphaxalone, diazepam, ethanol, or flumazenil reduced social interaction deficits during a later withdrawal, but pretreatment with PK11195 did not. In contrast, DMCM administered in lieu of early withdrawals increased social interaction deficits during an untreated later withdrawal. Locomotor deficits were significantly reversed only by the acute ethanol and diazepam treatment during the final withdrawal. Conclusions Single-dose administration of drugs that enhance or diminish activity at benzodiazepine

  18. Acute opioid withdrawal is associated with increased neural activity in reward-processing centers in healthy men: A functional magnetic resonance imaging study.

    PubMed

    Chu, Larry F; Lin, Joanne C; Clemenson, Anna; Encisco, Ellen; Sun, John; Hoang, Dan; Alva, Heather; Erlendson, Matthew; Clark, J David; Younger, Jarred W

    2015-08-01

    Opioid analgesics are frequently prescribed for chronic pain. One expected consequence of long-term opioid use is the development of physical dependence. Although previous resting state functional magnetic resonance imaging (fMRI) studies have demonstrated signal changes in reward-associated areas following morphine administration, the effects of acute withdrawal on the human brain have been less well-investigated. In an earlier study by our laboratory, ondansetron was shown to be effective in preventing symptoms associated with opioid withdrawal. The purpose of this current study was to characterize neural activity associated with acute opioid withdrawal and examine whether these changes are modified by ondansetron. Ten participants were enrolled in this placebo-controlled, randomized, double-blind, crossover study and attended three acute opioid withdrawal sessions. Participants received either placebo or ondansetron (8Ymg IV) before morphine administration (10Ymg/70Ykg IV). Participants then underwent acute naloxone-precipitated withdrawal during a resting state fMRI scan. Objective and subjective opioid withdrawal symptoms were assessed. Imaging results showed that naloxone-precipitated opioid withdrawal was associated with increased neural activity in several reward processing regions, including the right pregenual cingulate, putamen, and bilateral caudate, and decreased neural activity in networks involved in sensorimotor integration. Ondansetron pretreatment did not have a significant effect on the imaging correlates of opioid withdrawal. This study presents a preliminary investigation of the regional changes in neural activity during acute opioid withdrawal. The fMRI acute opioid withdrawal model may serve as a tool for studying opioid dependence and withdrawal in human participants. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast)

    PubMed Central

    Hutchinson, Mark R.; Lewis, Susannah S.; Coats, Benjamen D.; Skyba, David A.; Crysdale, Nicole Y.; Berkelhammer, Debra L.; Brzeski, Anita; Northcutt, Alexis; Vietz, Christine M.; Judd, Charles M.; Maier, Steven F.; Watkins, Linda R.; Johnson, Kirk W.

    2009-01-01

    Morphine-induced glial proinflammatory responses have been documented to contribute to tolerance to opioid analgesia. Here, we examined whether drugs previously shown to suppress glial proinflammatory responses can alter other clinically relevant opioid effects; namely, withdrawal or acute analgesia. AV411 (ibudilast) and minocycline, drugs with distinct mechanisms of action that result in attenuation of glial proinflammatory responses, each reduced naloxone-precipitated withdrawal. Analysis of brain nuclei associated with opioid withdrawal revealed that morphine altered expression of glial activation markers, cytokines, chemokines, and a neurotrophic factor. AV411 attenuated many of these morphine-induced effects. AV411 also protected against spontaneous withdrawal-induced hyperactivity and weight loss recorded across a 12-day timecourse. Notably, in the spontaneous withdrawal study, AV411 treatment was delayed relative to the start of the morphine regimen so to also test whether AV411 could still be effective in the face of established morphine dependence, which it was. AV411 did not simply attenuate all opioid effects, as co-administering AV411 with morphine or oxycodone caused 3-to-5-fold increases in acute analgesic potency, as revealed by leftward shifts in the analgesic dose response curves. Timecourse analyses revealed that plasma morphine levels were not altered by AV411, suggestive that potentiated analgesia was not simply due to prolongation of morphine exposure or increased plasma concentrations. These data support and extend similar potentiation of acute opioid analgesia by minocycline, again providing converging lines of evidence of glial involvement. Hence, suppression of glial proinflammatory responses can significantly reduce opioid withdrawal, whilst improving analgesia. PMID:18938237

  20. Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials.

    PubMed

    Mo, Yoonsun; Thomas, Michael C; Karras, George E

    2016-04-01

    To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS). A literature search of MEDLINE, EMBASE, and the Cochrane Library, together with a manual citation review was conducted. We selected English-language clinical trials (controlled and observational studies) evaluating the efficacy and safety of barbiturates compared with benzodiazepine (BZD) therapy for the treatment of AWS in the acute care setting. Data extracted from the included trials were duration of delirium, number of seizures, length of intensive care unit and hospital stay, cumulated doses of barbiturates and BZDs, and respiratory or cardiac complications. Seven studies consisting of 4 prospective controlled and 3 retrospective trials were identified. Results from all the included studies suggest that barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS. Although the evidence is limited, based on our findings, adding phenobarbital to a BZD-based regimen is a reasonable option, particularly in patients with BZD-refractory AWS. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Acute and chronic glue sniffing effects and consequences of withdrawal on aggressive behavior.

    PubMed

    Bouchatta, Otmane; Ouhaz, Zakaria; Ba-Mhamed, Saadia; Kerekes, Nóra; Bennis, Mohamed

    2016-05-01

    Drug abuse act on brain mechanisms that cause a high-risk individual to engage in aggressive and violent behavior. While a drug-violence relationship exists, the nature of this relationship is often complex, with intoxication, neurotoxic, and withdrawal effects often being confused and/or confounded. Glue sniffing is often a springboard to the abuse of more addictive drugs. Despite its high prevalence and serious consequences, we know relatively little about the aggressive behavioral effects of volatile inhalants abuse, especially glue. The aim of the present study was to investigate the link between the duration of glue exposure, a common substance abuse problem in Morocco, and the level of aggressive behavior during withdrawal. For this we used the isolation-induced aggression model "residents" in three groups of mice. The first group served as control resident animals (n=10, without exposure); the second group as experimental resident mice (n=10) tested before and after acute (first day) and chronic exposure to the glue, and at 1 and 2weeks of withdrawal; and the third group of 10 intruder animals. The results showed that the number of attacks decreased (halved) and the latency of the first attack increased (doubled) following acute glue sniffing. However, the effects of chronic exposure and of 1week of withdrawal led to an increase in the intensity of agonistic encounters. After 2weeks of withdrawal, the intensity of aggressive behavior decreased again. These results indicated that chronic glue exposure and the first week of withdrawal are associated with increased aggression in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Molecular basis of alcoholism.

    PubMed

    Most, Dana; Ferguson, Laura; Harris, R Adron

    2014-01-01

    Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy. © 2014 Elsevier B.V. All rights reserved.

  3. Electrocardiogram Changes with Acute Alcohol Intoxication: A Systematic Review.

    PubMed

    Raheja, Hitesh; Namana, Vinod; Chopra, Kirti; Sinha, Ankur; Gupta, Sushilkumar Satish; Kamholz, Stephan; Moskovits, Norbert; Shani, Jacob; Hollander, Gerald

    2018-01-01

    Acute alcohol intoxication has been associated with cardiac arrhythmias but the electrocardiogram (ECG) changes associated with acute alcohol intoxication are not well defined in the literature. Highlight the best evidence regarding the ECG changes associated with acute alcohol intoxication in otherwise healthy patients and the pathophysiology of the changes. A literature search was carried out; 4 studies relating to ECG changes with acute alcohol intoxication were included in this review. Of the total 141 patients included in the review, 90 (63.8%) patients had P-wave prolongation, 80 (56%) patients had QTc prolongation, 19 (13.5%) patients developed T-wave abnormalities, 10 (7%) patients had QRS complex prolongation, 3 (2.12%) patients developed ST-segment depressions. The most common ECG changes associated with acute alcohol intoxication are (in decreasing order of frequency) P-wave and QTc prolongation, followed by T-wave abnormalities and QRS complex prolongation. Mostly, these changes are completely reversible.

  4. Effects of repeated withdrawal from alcohol on recovery of cognitive impairment under abstinence and rate of relapse.

    PubMed

    Loeber, Sabine; Duka, Theodora; Welzel Márquez, Helga; Nakovics, Helmut; Heinz, Andreas; Mann, Karl; Flor, Herta

    2010-01-01

    Several authors suggest that withdrawal from alcohol could cause neurotoxic lesions in the frontal lobe and thereby affect cognitive function. In line with this, previous studies have demonstrated greater cognitive impairment of alcohol-dependent patients with two or more previous detoxifications (Hi-detox) compared with patients with less than two detoxifications (Lo-detox). The aim of the present study was to investigate whether repeated withdrawal from alcohol affects recovery of cognitive function and is related to relapse. Forty-eight alcohol-dependent patients (Hi-detox: n = 31, Lo-detox: n = 17) and 36 healthy controls underwent a comprehensive neuropsychological test-battery. Patients were tested after completion of detoxification (T1) and 3 (T2, n = 35) and 6 (T3, n = 28) months after discharge. Healthy controls were tested at T1 (n = 36) and T2 (n = 16). Drinking behaviour was assessed at all times. Patients performed significantly worse than controls at T1 as well as T2 with regard to attention/executive function. Recovery of attention/executive function was observed within the second 3 months after discharge, but the Hi-detox group performed worse than the Lo-detox group. No association with relapse was observed. This study provides first evidence, that repeated withdrawal from alcohol might be associated with reduced brain plasticity as indicated by a delay of recovery from impairment of attention/executive function. However, little evidence was found for a direct influence of cognitive impairment on treatment success.

  5. Effects of acute caffeine withdrawal on Short Category Test performance in sleep-deprived individuals.

    PubMed

    Killgore, William D S; Kahn-Greene, Ellen T; Killgore, Desiree B; Kamimori, Gary H; Balkin, Thomas J

    2007-12-01

    Caffeine is a popular stimulant often used to counter the effects of sleep loss and fatigue. Withdrawal from caffeine may produce mild declines in simple cognitive capacities such as attention and concentration, but it is unclear whether more complex cognitive functions, such as abstract reasoning or concept formation, may be similarly affected. To assess the effect of acute caffeine withdrawal on executive functioning during sleep deprivation, 26 healthy volunteers were administered in double-blind form either repeated doses of caffeine or placebo over two nights of continuous wakefulness. The 108-item Short Category Test was administered after 56 hr. of total sleep deprivation (9 hr. post-caffeine administration). The caffeine group scored significantly more poorly, making approximately 57% more errors on the test than the placebo group. These findings suggest that acute caffeine withdrawal during prolonged sleep deprivation has an adverse effect on abstract reasoning and concept formation.

  6. Acute withdrawal but not long-term withdrawal from methamphetamine affects sexual behavior in female rats.

    PubMed

    Thibodeau, Rachel B; Ornelas, Laura C; Romero, Jordan; Memos, Nicoletta; Scheible, Matthew; Avila, Alfred; Schumacher, Abby; Navarro, April; Zimmermann, Karen; Cuenod, Bethany A; Frohardt, Russell J; Guarraci, Fay A

    2013-02-01

    The present study was designed to investigate the long-term effects of repeated methamphetamine (MA) exposure on sexual motivation in female rats tested after a period of drug abstinence. In Experiment 1, female subjects received three injections of MA (1.0mg/kg/day, every other day) or saline and were tested for paced mating behavior (where females could control the receipt of sexual stimulation from one male rat) 21 days after their last injection. In Experiment 2, female subjects received 12 consecutive injections of MA (1.0mg/kg/day) or saline and were tested for mate choice (where females could control the receipt of sexual stimulation from two male rats simultaneously) 6 days after their last injection. Experiment 3 was identical to Experiment 2 except that female subjects received no baseline mating test and were tested for mate choice 24h and 6 days after their last injection. Open field tests were conducted in each experiment to measure locomotor activity after repeated exposure to MA. Although repeated MA exposure increased locomotor activity, mating behavior was not facilitated after either a short (6 days) or long (21 days) period of drug abstinence. Nevertheless, sexual behavior was disrupted during the 24h acute withdrawal period. Therefore, although the present study found no evidence of cross-sensitization between female sexual behavior and MA after either a short or a long period of drug abstinence, sexual behavior in sexually naïve female rats is sensitive to the depressive state associated with acute withdrawal from MA. In conclusion, the results of the present study suggest that MA acts differently from other psychomotor stimulants, and that the effects of MA withdrawal on sexual behavior differ between male and female rats. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. A systematic nurse-led approach to withdrawal risk screening, prevention and treatment among inpatients with an alcohol use disorder in an ear, nose, throat and jaw surgery department-A formative evaluation.

    PubMed

    Leuenberger, Deborah Linda; Fierz, Katharina; Hinck, Andreas; Bodmer, Daniel; Hasemann, Wolfgang

    2017-02-01

    Among patients with head and neck cancer comorbid alcohol use disorder is frequent which contributes to higher risk of developing perioperative alcohol withdrawal syndrome/delirium or delirium due to medical conditions. Although guidelines emphasize prevention and treatment of alcohol withdrawal in hospitalized patients, a validated systematic approach for management of these patients is still lacking. Our aim was to formatively evaluate our newly developed systematic approach in view of nurses' adherence to screening patients for regular alcohol consumption and managing their withdrawal symptoms using the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised. We conducted a formative evaluation to improve the project's design and performance and used a retrospective chart review in a consecutive sample of all adult inpatients with head and neck cancer being assigned for surgery in a university hospital. Our bundle of interventions consisted of nurses' screenings for regular alcohol consumption, withdrawal risk assessment, offering patients a substitution therapy, nurses' assessments of withdrawal symptoms and symptom oriented withdrawal management. Proximate endpoints were analyzed descriptively at each component of the bundle in terms of frequencies and severity of withdrawal symptoms, frequencies of nurses' and doctors' screenings and nurses' assessments performed as required. Between 2013 and 2014, 87 inpatients met inclusion criteria and screenings by doctors/ nurses revealed 49 alcohol consumers, where six screenings were omitted by nurses and six by doctors. Twenty-one consumers were at risk and six of them developed an alcohol withdrawal syndrome. None of the 87 showed an alcohol withdrawal delirium, but five developed a delirium due to medical conditions. Nurses correctly conducted all preventive elements of the intervention bundle in 14 (58%) patients at risk but overall, only performed 50% of the required assessments. Although nurses safely

  8. Emergency Department Frequent Users for Acute Alcohol Intoxication.

    PubMed

    Klein, Lauren R; Martel, Marc L; Driver, Brian E; Reing, Mackenzie; Cole, Jon B

    2018-03-01

    A subset of frequent users of emergency services are those who use the emergency department (ED) for acute alcohol intoxication. This population and their ED encounters have not been previously described. This was a retrospective, observational, cohort study of patients presenting to the ED for acute alcohol intoxication between 2012 and 2016. We collected all data from the electronic medical record. Frequent users for alcohol intoxication were defined as those with greater than 20 visits for acute intoxication without additional medical chief complaints in the previous 12 months. We used descriptive statistics to evaluate characteristics of frequent users for alcohol intoxication, as well as their ED encounters. We identified 32,121 patient encounters. Of those, 325 patients were defined as frequent users for alcohol intoxication, comprising 11,370 of the encounters during the study period. The median maximum number of encounters per person for alcohol intoxication in a one-year period was 47 encounters (range 20 to 169). Frequent users were older (47 years vs. 39 years), and more commonly male (86% vs. 71%). Frequent users for alcohol intoxication had higher rates of medical and psychiatric comorbidities including liver disease, chronic kidney disease, ischemic vascular disease, dementia, chronic obstructive pulmonary disease, history of traumatic brain injury, schizophrenia, and bipolar disorder. In this study, we identified a group of ED frequent users who use the ED for acute alcohol intoxication. This population had higher rates of medical and psychiatric comorbidities compared to non-frequent users.

  9. Gene expression profile analysis of rat cerebellum under acute alcohol intoxication.

    PubMed

    Zhang, Yu; Wei, Guangkuan; Wang, Yuehong; Jing, Ling; Zhao, Qingjie

    2015-02-25

    Acute alcohol intoxication, a common disease causing damage to the central nervous system (CNS) has been primarily studied on the aspects of alcohol addiction and chronic alcohol exposure. The understanding of gene expression change in the CNS during acute alcohol intoxication is still lacking. We established a model for acute alcohol intoxication in SD rats by oral gavage. A rat cDNA microarray was used to profile mRNA expression in the cerebella of alcohol-intoxicated rats (experimental group) and saline-treated rats (control group). A total of 251 differentially expressed genes were identified in response to acute alcohol intoxication, in which 208 of them were up-regulated and 43 were down-regulated. Gene ontology (GO) term enrichment analysis and pathway analysis revealed that the genes involved in the biological processes of immune response and endothelial integrity are among the most severely affected in response to acute alcohol intoxication. We discovered five transcription factors whose consensus binding motifs are overrepresented in the promoter region of differentially expressed genes. Additionally, we identified 20 highly connected hub genes by co-expression analysis, and validated the differential expression of these genes by real-time quantitative PCR. By determining novel biological pathways and transcription factors that have functional implication to acute alcohol intoxication, our study substantially contributes to the understanding of the molecular mechanism underlying the pathology of acute alcoholism. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Accidental acute alcohol intoxication in infants: review and case report.

    PubMed

    Minera, Gabriella; Robinson, Evan

    2014-11-01

    Acute alcohol intoxication in children younger than 18 months old is both rarely documented and rarely fatal. Previous case reports suggest hypoglycemia and faster than normal rates of alcohol elimination found in children with acute alcohol intoxication compared with adults, but data are lacking. A 2-month-old infant presented with a decreased mental status after accidental ingestion of alcohol. He was diagnosed with acute alcohol intoxication, with a blood alcohol level of 330 mg/dL and was hyperglycemic (167 mg/dL). Alcohol elimination rate was calculated to be 21.6 mg/dL/h, similar to that in adults. To our knowledge, this case is the second youngest documented patient with accidental alcohol intoxication via ingestion in the United States. We present a rare case report of acute alcohol intoxication in an infant and a review of the literature. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although rare in the literature, poison control data suggests that alcohol poisoning in very young children is not rare. Emergency physicians should be prepared for the management of infants with alcohol poisoning. This case report and review brings attention to this subject and briefly discusses ethanol metabolism in infants. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.

    PubMed

    Alaux-Cantin, Stéphanie; Buttolo, Romain; Houchi, Hakim; Jeanblanc, Jérôme; Naassila, Mickaël

    2015-09-01

    Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50 mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25 mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6 hours after treatment in ND rats, it was long lasting in PD rats (at least 30 hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. © 2014 Society for the Study of Addiction.

  12. Using the AUDIT-PC to predict alcohol withdrawal in hospitalized patients.

    PubMed

    Pecoraro, Anna; Ewen, Edward; Horton, Terry; Mooney, Ruth; Kolm, Paul; McGraw, Patty; Woody, George

    2014-01-01

    Alcohol withdrawal syndrome (AWS) occurs when alcohol-dependent individuals abruptly reduce or stop drinking. Hospitalized alcohol-dependent patients are at risk. Hospitals need a validated screening tool to assess withdrawal risk, but no validated tools are currently available. To examine the admission Alcohol Use Disorders Identification Test-(Piccinelli) Consumption (AUDIT-PC) ability to predict the subsequent development of AWS among hospitalized medical-surgical patients admitted to a non-intensive care setting. Retrospective case–control study of patients discharged from the hospital with a diagnosis of AWS. All patients with AWS were classified as presenting with AWS or developing AWS later during admission. Patients admitted to an intensive care setting and those missing AUDIT-PC scores were excluded from analysis. A hierarchical (by hospital unit) logistic regression was performed and receiver-operating characteristics were examined on those developing AWS after admission and randomly selected controls. Because those diagnosing AWS were not blinded to the AUDIT-PC scores, a sensitivity analysis was performed. The study cohort included all patients age ≥18 years admitted to any medical or surgical units in a single health care system from 6 October 2009 to 7 October 2010. After exclusions, 414 patients were identified with AWS. The 223 (53.9 %) who developed AWS after admission were compared to 466 randomly selected controls without AWS. An AUDIT-PC score ≥4 at admission provides 91.0 % sensitivity and 89.7 % specificity (AUC=0.95; 95 % CI, 0.94–0.97) for AWS, and maximizes the correct classification while resulting in 17 false positives for every true positive identified. Performance remained excellent on sensitivity analysis (AUC=0.92; 95 % CI, 0.90–0.93). Increasing AUDIT-PC scores were associated with an increased risk of AWS (OR=1.68, 95 % CI 1.55–1.82, p<0.001). The admission AUDIT-PC score is an excellent discriminator of AWS and could be

  13. Implementing managed alcohol programs in hospital settings: A review of academic and grey literature.

    PubMed

    Brooks, Hannah L; Kassam, Shehzad; Salvalaggio, Ginetta; Hyshka, Elaine

    2018-04-01

    People with severe alcohol use disorders are at increased risk of poor acute-care outcomes, in part due to difficulties maintaining abstinence from alcohol while hospitalised. Managed alcohol programs (MAP), which administer controlled doses of beverage alcohol to prevent withdrawal and stabilise drinking patterns, are one strategy for increasing adherence to treatment, and improving health outcomes for hospital inpatients with severe alcohol use disorders. Minimal research has examined the implementation of MAPs in hospital settings. We conducted a scoping review to describe extant literature on MAPs in community settings, as well as the therapeutic provision of alcohol to hospital inpatients, to assess the feasibility of implementing formal MAPs in hospital settings and identify knowledge gaps requiring further study. Four academic and 10 grey literature databases were searched. Evidence was synthesised using quantitative and qualitative approaches. Forty-two studies met review inclusion criteria. Twenty-eight examined the administration of alcohol to hospital inpatients, with most reporting positive outcomes related to prevention or treatment of alcohol withdrawal. Fourteen studies examined MAPs in the community and reported that they help stabilise drinking patterns, reduce alcohol-related harms and facilitate non-judgemental health and social care. MAPs in the community have been well described and research has documented effective provision of alcohol in hospital settings for addressing withdrawal. Implementing MAPs as a harm reduction approach in hospital settings is potentially feasible. However, there remains a need to build off extant literature and develop and evaluate standardised MAP protocols tailored to acute-care settings. © 2018 Australasian Professional Society on Alcohol and other Drugs.

  14. Preclinical Evaluation of Riluzole: Assessments of Ethanol Self-Administration and Ethanol Withdrawal Symptoms

    PubMed Central

    Besheer, Joyce; Lepoutre, Veronique; Hodge, Clyde W.

    2010-01-01

    Background Many of the neurobehavioral effects of ethanol are mediated by inhibition of excitatory N-methyl-d-aspartate (NMDA) and enhancement of inhibitory γ-amino-butyric-acid (GABA) receptor systems. There is growing interest in drugs that alter these systems as potential medications for problems associated with alcoholism. The drug riluzole, approved for treatment of amyotrophic lateral sclerosis (ALS), inhibits NMDA and enhances GABAA receptor system activity. This study was designed to determine the preclinical efficacy of riluzole to modulate ethanol self-administration and withdrawal. Methods Male C57BL/6J mice were trained to lever press on a concurrent fixed-ratio 1 schedule of ethanol (10% v/v) versus water reinforcement during daily 16-hour sessions. Riluzole (1 to 40 mg/kg, IP) was evaluated on ethanol self-administration after acute and chronic (2 week) treatment. To determine if riluzole influences ethanol withdrawal-associated seizures, mice were fed an ethanol-containing or control liquid diet for 18 days. The effects of a single injection of riluzole (30 mg/kg) were examined on handling-induced convulsions after ethanol withdrawal. Results Acute riluzole (30 and 40 mg/kg) reduced ethanol self-administration during the first 4 hours of the session, which corresponds to the known pharmacokinetics of this drug. Ethanol self-administration was also reduced by riluzole after chronic treatment. Riluzole (30 mg/kg) significantly decreased the severity of ethanol-induced convulsions 2 hours after ethanol withdrawal. Conclusions These results demonstrate that riluzole decreases ethanol self-administration and may reduce ethanol withdrawal severity in mice. Thus, riluzole may have utility in the treatment of problems associated with alcoholism. PMID:19426166

  15. Developmental Effects of Acute, Chronic, and Withdrawal from Chronic Nicotine on Fear Conditioning

    PubMed Central

    Portugal, George S.; Wilkinson, Derek S.; Turner, Jill R.; Blendy, Julie A.; Gould, Thomas J.

    2012-01-01

    Pre-adolescence and adolescence are developmental periods associated with increased vulnerability for tobacco addiction, and exposure to tobacco during these periods may lead to long-lasting changes in behavioral and neuronal plasticity. The present study examined the short- and long-term effects of nicotine and nicotine withdrawal on fear conditioning in pre-adolescent, adolescent, and adult mice, and potential underlying substrates that may mediate the developmental effects of nicotine, such as changes in nicotinic acetylcholine receptor (nAChR) binding, CREB expression, and nicotine metabolism. Age-related differences existed in sensitivity to the effects of acute nicotine, chronic nicotine and nicotine withdrawal on contextual fear conditioning (no changes in cued fear conditioning were seen); younger mice were more sensitive to the acute effects and less sensitive to the effects of nicotine withdrawal 24 hours post treatment cessation. Developmental differences in nAChR binding were associated with the effects of nicotine withdrawal on contextual learning. Developmental differences in nicotine metabolism and CREB expression were also observed, but were not related to the effects of nicotine withdrawal on contextual learning 24 hours post treatment. Chronic nicotine exposure during pre-adolescence or adolescence, however, produced long-lasting impairments in contextual learning that were observed during adulthood, whereas adult chronic nicotine exposure did not. These developmental effects could be related to changes in CREB. Overall, there is a developmental shift in the effects of nicotine on hippocampus-dependent learning and developmental exposure to nicotine results in adult cognitive deficits; these changes in cognition may play an important role in the development and maintenance of nicotine addiction. PMID:22521799

  16. Drinking status but not acute alcohol consumption influences delay discounting.

    PubMed

    Adams, Sally; Attwood, Angela S; Munafò, Marcus R

    2017-09-01

    The aim of this study was to investigate the following: (a) the effects of acute alcohol on delay discounting; (b) the effects of drinking status on delayed discounting; and (c) whether these effects differ according to reward type (alcohol vs. money). Heavy and light social alcohol users (n = 96) were randomized to receive either an acute dose of alcohol at 0.4 or 0.6 g/kg or placebo in a between-subjects, double-blind design. Delay discounting of alcohol and monetary rewards was measured using a hyperbolic model, with higher scores indicative of greater delay discounting. ANOVA of discount scores indicated a main effect of reward type, where all participants had higher discount scores for alcohol versus money rewards. A main effect of drinking status was also observed, where heavier drinkers had higher discount scores compared with lighter drinkers. We did not observe a main effect of acute alcohol use on delay discounting or the hypothesized interactions between acute alcohol use and drinking status with reward type. Our data suggest that heavier drinkers discount the value of delayed rewards more steeply than lighter drinkers. Delay discounting may therefore be a promising marker of heavy alcohol consumption in social drinkers. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus.

    PubMed

    Pereira, Pedro A; Rocha, João P; Cardoso, Armando; Vilela, Manuel; Sousa, Sérgio; Madeira, M Dulce

    2016-05-01

    Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats.

    PubMed

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects.

  19. Acute Alcohol Intoxication Exacerbates Rhabdomyolysis-Induced Acute Renal Failure in Rats

    PubMed Central

    Tsai, Jen-Pi; Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Hsu, Bang-Gee

    2017-01-01

    Traumatic and nontraumatic rhabdomyolysis can lead to acute renal failure (ARF), and acute alcohol intoxication can lead to multiple abnormalities of the renal tubules. We examined the effect of acute alcohol intoxication in a rat model of rhabdomyolysis and ARF. Intravenous injections of 5 g/kg ethanol were given to rats over 3 h, followed by glycerol-induced rhabdomyolysis. Biochemical parameters, including blood urea nitrogen (BUN), creatinine (Cre), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), and creatine phosphokinase (CPK), were measured before and after induction of rhabdomyolysis. Renal tissue injury score, renal tubular cell expression of E-cadherin, nuclear factor-κB (NF-κB), and inducible nitric oxide synthase (iNOS) were determined. Relative to rats in the vehicle group, rats in the glycerol-induced rhabdomyolysis group had significantly increased serum levels of BUN, Cre, GOT, GPT, and CPK, elevated renal tissue injury scores, increased expression of NF-κB and iNOS, and decreased expression of E-cadherin. Ethanol exacerbated all of these pathological responses. Our results suggest that acute alcohol intoxication exacerbates rhabdomyolysis-induced ARF through its pro-oxidant and inflammatory effects. PMID:28824301

  20. Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit Disorder

    PubMed Central

    2012-01-01

    Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of specific neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreased dopamine and γ-aminobutyric acid function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and that may contribute to the negative motivational state

  1. Acute alcohol intoxication-induced microvascular leakage.

    PubMed

    Doggett, Travis M; Breslin, Jerome W

    2014-09-01

    Alcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication increases microvascular permeability and investigated potential signaling mechanisms in endothelial cells that may be involved. Conscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered fluorescein isothiocyanate (FITC)-conjugated albumin (FITC-albumin) from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial-specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen-activated protein kinase (MAPK), myosin light-chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE-cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation was assessed by ELISA assays. Alcohol significantly increased FITC-albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE-cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of alcohol dehydrogenase or application of a superoxide dismutase mimetic failed to prevent alcohol-induced decreases in TER. Inhibition of p38 MAPK, but not MLCK or ROCK, significantly attenuated the alcohol-induced barrier dysfunction. Alcohol rapidly decreased GTP-bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol-induced barrier dysfunction quickly resolved TER to baseline levels. Our results suggest that

  2. Incidence rates of admissions associated with alcohol withdrawal syndrome in Spain: Analysis of minimum basic data set 1999-2010.

    PubMed

    Gómez-Méndez, Raquel; Monte-Secades, Rafael; Ventura-Valcárcel, Pablo; Rabuñal-Rey, Ramón; Guerrero-Sande, Héctor; Chamorro-Fernández, Antonio J; Pértega-Díaz, Sonia

    2017-12-20

    There are no data on the incidence of admissions associated with alcohol withdrawal syndrome (AWS) or about its trend over time in Spain. To analyze the characteristics, incidence rates and trends over time of hospital admissions associated with AWS in Spanish public hospitals. Analysis from the Spanish public hospitals minimum basic data set of hospital admissions with AWS (CIE9-MC 291.81), alcohol withdrawal delirium (CIE9-MC 291.0) and alcohol withdrawal hallucinosis (CIE9-MC 291.3), since 1999 to 2010. We identified 56,395 admissions associated with AWS. Mean age was 50.9 (SD 12.5) and 88% were male. The most frequent admission department was Internal Medicine (24.9%). The mean hospital stay was 12.6 days (SD 14.4) and mortality was 4.7%; 62.6% of cases developed AWS during an admission for another reason, mostly due to alcohol-related pathologies. Secondary diagnoses in patients hospitalized for AWS were related to alcohol consumption in more than half of the cases. The incidence rate of admissions associated with AWS in Spain remained stable from 1999 to 2010, with a small decline in the last 3 years of the period. The communities with the highest incidence were the Canary Islands, the Balearic Islands and Galicia. The incidence rate of admissions associated with AWS in Spanish public hospitals in the period 1999-2010 has remained stable with slight changes. There are differences in the incidence of AWS among the different autonomous communities. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  3. Diagnosis‐based emergency department alcohol harm surveillance: What can it tell us about acute alcohol harms at the population level?

    PubMed Central

    Dinh, Michael; Rodgers, Craig; Muscatello, David J.; McGuire, Rhydwyn; Ryan, Therese; Thackway, Sarah

    2016-01-01

    Abstract Introduction and Aims Acute harm from heavy drinking episodes is an increasing focus of public health policy, but capturing timely data on acute harms in the population is challenging. This study aimed to evaluate the precision of readily available administrative emergency department (ED) data in public health surveillance of acute alcohol harms. Design and Methods We selected a random sample of 1000 ED presentations assigned an ED diagnosis code for alcohol harms (the ‘alcohol syndrome’) in the New South Wales, Australia, automatic syndromic surveillance system. The sample was selected from 68 public hospitals during 2014. Nursing triage free‐text fields were independently reviewed to confirm alcohol consumption and classify each presentation into either an ‘acute’ or ‘chronic’ harm. Positive predictive value (PPV) for acute harm was calculated, and predictors of acute harm presentations were estimated using logistic regression. Results The PPV of the alcohol syndrome for acute alcohol harm was 53.5%. Independent predictors of acute harm were ambulance arrival [adjusted odds ratio (aOR) = 3.4, 95% confidence interval (CI) 2.4–4.7], younger age (12–24 vs. 25–39 years: aOR = 3.4, 95% CI 2.2–5.3), not being admitted (aOR 2.2, 95% CI 1.5–3.2) and arriving between 10 pm and 5.59 am (aOR 2.1, 95% CI 1.5–2.8). PPV among 12 to 24‐year‐olds was 82%. Discussion and Conclusions The alcohol syndrome provides moderate precision as an indicator of acute alcohol harms presenting to the ED. Precision for monitoring acute harm in the population is improved by filtering the syndrome by the strongest independent predictors of acute alcohol harm presentations. [Whitlam G, Dinh M, Rodgers C, Muscatello DJ, McGuire R, Ryan T, Thackway S. Diagnosis‐based emergency department alcohol harm surveillance: What can it tell us about acute alcohol harms at the population level? Drug Alcohol Rev 2016;35:693–701] PMID:27786390

  4. Repeated diazepam administration reversed working memory impairments and glucocorticoid alterations in the prefrontal cortex after short but not long alcohol-withdrawal periods.

    PubMed

    Dominguez, G; Henkous, N; Pierard, C; Belzung, C; Mons, N; Beracochea, Daniel

    2018-04-30

    The study was designed to assess whether repeated administration of diazepam (Valium®, Roche)-a benzodiazepine exerting an agonist action on GABA A receptors-may alleviate both the short (1 week, 1W) and long-term (6 weeks, 6W) deleterious effects of alcohol withdrawal occurring after chronic alcohol consumption (6 months; 12% v/v) in C57/BL6 male mice. More pointedly, we first evidenced that 1W and 6W alcohol-withdrawn mice exhibited working memory deficits in a sequential alternation task, associated with sustained exaggerated corticosterone rise and decreased pCREB levels in the prefrontal cortex (PFC). In a subsequent experiment, diazepam was administered i.p. for 9 consecutive days (1 injection/day) during the alcohol withdrawal period at decreasing doses ranging from 1.0 mg/kg to 0.25 mg/kg. Diazepam was not detected in the blood of withdrawn mice at the time of memory testing, occurring 24 hours after the last diazepam injection. Repeated diazepam administration significantly improved alternation rates and normalized levels of glucocorticoids and pCREB activity in the PFC in 1W but not in 6W withdrawn mice. Thus, repeated diazepam administration during the alcohol-withdrawal period only transitorily canceled out the working memory impairments and glucocorticoid alterations in the PFC of alcohol-withdrawn animals.

  5. Implementation of an Intensive Care Unit-Specific Alcohol Withdrawal Syndrome Management Protocol Reduces the Need for Mechanical Ventilation.

    PubMed

    Heavner, Jason J; Akgün, Kathleen M; Heavner, Mojdeh S; Eng, Claire C; Drew, Matthew; Jackson, Peter; Pritchard, David; Honiden, Shyoko

    2018-05-25

    Alcohol use disorders are prevalent and put patients at risk for developing alcohol withdrawal syndrome (AWS). Treatment of AWS with a symptom-triggered protocol standardizes management and may avoid AWS-related complications. The objective of this study was to evaluate whether implementation of an intensive care unit (ICU)-specific, symptom-triggered protocol for management of AWS was associated with improved clinical outcomes and, in particular, would reduce the risk of patients with AWS requiring mechanical ventilation. Retrospective pre-post-protocol implementation study. Thirty-six-bed, closed medical ICU (MICU) at a large, tertiary care, teaching hospital in an urban setting. A total of 233 adults admitted to the MICU with any diagnosis of alcohol use disorders based on International Classification of Diseases, Ninth Revision codes and who received at least one dose of any benzodiazepine; of these patients, 139 were in the pre-protocol era (August 2009-January 2010 and August 2010-January 2011), and 94 were in the post-protocol era (August 2012-January 2013), after implementation of the Yale Alcohol Withdrawal Protocol (YAWP) in April 2012. The YAWP pairs a modified Minnesota Detoxification Scale with an order set that includes benzodiazepine dosing regimens and suggests adjuvant therapies. AWS was the primary reason for ICU admission (107/233 patients [45.9%]) and did not significantly vary between eras (P=0.2). Of the 233 patients included, 81.1% were male and 67.0% were white, which did not significantly differ by study era. Severity of illness at MICU admission did not significantly differ between patients in the pre-protocol and post-protocol eras (median [interquartile range] Acute Physiology and Chronic Health Evaluation [APACHE] II scores of 12 [9-17] and 12.5 [7-16], respectively, p=0.4). Median lorazepam-equivalent dose per MICU day, duration of benzodiazepine infusion, and use of adjuvant therapy were not significantly different between eras. MICU

  6. 27 CFR 19.1002 - Prohibited uses, transfers, and withdrawals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... person shall withdraw, use, sell, or otherwise dispose of distilled spirits (including fuel alcohol... withdraws, uses, sells or otherwise disposes of distilled spirits (including fuel alcohol) produced under... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Prohibited uses, transfers...

  7. Double dissociation in the neural substrates of acute opiate dependence as measured by withdrawal-potentiated startle.

    PubMed

    Harris, A C; Atkinson, D M; Aase, D M; Gewirtz, J C

    2006-01-01

    The basolateral amygdala and portions of the "extended" amygdala (i.e. central nucleus of the amygdala, bed nucleus of the stria terminalis and shell of the nucleus accumbens) have been implicated in the aversive aspects of withdrawal from chronic opiate administration. Given that similar withdrawal signs are observed following a single opiate exposure, these structures may also play a role in "acute opiate dependence." In the current study, drug-naïve rats underwent naloxone-precipitated withdrawal from acute morphine (10 mg/kg) exposure on two successive days. On either the first or second day of testing, the basolateral amygdala, central nucleus of the amygdala, bed nucleus of the stria terminalis, or nucleus accumbens was temporarily inactivated immediately prior to naloxone injection by microinfusion of the glutamatergic alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulfonamide (3 microg/0.5 microl). On the first day, inactivation of the basolateral amygdala, central nucleus of the amygdala, or bed nucleus of the stria terminalis, but not the nucleus accumbens blocked withdrawal-potentiated startle, a behavioral measure of the anxiogenic effects of withdrawal. On the second day, inactivation of the nucleus accumbens, but not the basolateral amygdala, central nucleus of the amygdala, or bed nucleus of the stria terminalis disrupted the withdrawal effect. Effects of structural inactivations on withdrawal-potentiated startle were not influenced by differences in withdrawal severity on the two days of testing. A fear-potentiated startle procedure provided functional confirmation of correct cannulae placement in basolateral amygdale- and central nucleus of the amygdala-implanted animals. Our findings indicate a double dissociation in the neural substrates of withdrawal-potentiated startle following a first versus second morphine exposure, and may reflect a reorganization of

  8. Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice.

    PubMed

    Hwa, Lara S; Nathanson, Anna J; Shimamoto, Akiko; Tayeh, Jillian K; Wilens, Allison R; Holly, Elizabeth N; Newman, Emily L; DeBold, Joseph F; Miczek, Klaus A

    2015-08-01

    Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20 % EtOH. Aggressive and nonaggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5-mg/kg dose in mice with a history of 8 weeks of EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks of EtOH compared to 1 week of EtOH or 8 weeks of water. Five milligrams per kilogram of memantine increased glutamate in 8-week EtOH mice, but also in 1-week EtOH and water drinkers. These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior.

  9. Aggression and increased glutamate in the mPFC during withdrawal from intermittent alcohol in outbred mice

    PubMed Central

    Hwa, Lara S.; Nathanson, Anna J.; Shimamoto, Akiko; Tayeh, Jillian K.; Wilens, Allison R.; Holly, Elizabeth N.; Newman, Emily L.; DeBold, Joseph F.; Miczek, Klaus A.

    2015-01-01

    Rationale Disrupted social behavior, including occasional aggressive outbursts, is characteristic of withdrawal from long-term alcohol (EtOH) use. Heavy EtOH use and exaggerated responses during withdrawal may be treated using glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonists. Objectives The current experiments explore aggression and medial prefrontal cortex (mPFC) glutamate as consequences of withdrawal from intermittent access to EtOH, and changes in aggression and mPFC glutamate caused by NMDAR antagonists memantine and ketamine. Methods Swiss male mice underwent withdrawal following 1-8 weeks of intermittent access to 20% EtOH. Aggressive and non-aggressive behaviors with a conspecific were measured 6-8 h into EtOH withdrawal after memantine or ketamine (0-30 mg/kg, i.p.) administration. In separate mice, extracellular mPFC glutamate after memantine was measured during withdrawal using in vivo microdialysis. Results At 6-8 h withdrawal from EtOH, mice exhibited more convulsions and aggression, and decreased social contact compared to age-matched water controls. Memantine, but not ketamine, increased withdrawal aggression at the 5 mg/kg dose in mice with a history of 8 weeks EtOH but not 1 or 4 weeks of EtOH or in water drinkers. Tonic mPFC glutamate was higher during withdrawal after 8 weeks EtOH compared to 1 week EtOH or 8 weeks water. Five mg/kg memantine increased glutamate in 8 week EtOH mice, but also in 1 week EtOH and water drinkers. Conclusions These studies reveal aggressive behavior as a novel symptom of EtOH withdrawal in outbred mice and confirm a role of NMDARs during withdrawal aggression and for disrupted social behavior. PMID:25899790

  10. Acute Alcoholic Hepatitis: Therapy.

    PubMed

    Phillips, Paulina K; Lucey, Michael R

    2016-08-01

    Alcoholic hepatitis (AH) causes great morbidity and mortality in the United States and throughout the world. Advances in therapy have proven difficult. In part, this reflects challenges in diagnosis, including the distinction between AH and acute-on-chronic liver failure. Liver biopsy is the best method to clarify the cause in circumstances whereby conflicting clinical data confound the diagnosis. All treatment of AH begins with abstinence from alcohol. All patients with AH should be given sufficient nutrition. Prednisolone has become the principal agent for treating patients with severe AH. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Quantifying alcohol-related emergency admissions in a UK tertiary referral hospital: a cross-sectional study of chronic alcohol dependency and acute alcohol intoxication

    PubMed Central

    Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R

    2016-01-01

    Objectives Alcohol is responsible for a proportion of emergency admissions to hospital, with acute alcohol intoxication and chronic alcohol dependency (CAD) implicated. This study aims to quantify the proportion of hospital admissions through our emergency department (ED) which were thought by the admitting doctor to be (largely or partially) a result of alcohol consumption. Setting ED of a UK tertiary referral hospital. Participants All ED admissions occurring over 14 weeks from 1 September to 8 December 2012. Data obtained for 5497 of 5746 admissions (95.67%). Primary outcome measures Proportion of emergency admissions related to alcohol as defined by the admitting ED clinician. Secondary outcome measures Proportion of emergency admissions due to alcohol diagnosed with acute alcohol intoxication or CAD according to ICD-10 criteria. Results 1152 (21.0%, 95% CI 19.9% to 22.0%) of emergency admissions were thought to be due to alcohol. 74.6% of patients admitted due to alcohol had CAD, and significantly greater than the 26.4% with ‘Severe’ or ‘Very Severe’ acute alcohol intoxication (p<0.001). Admissions due to alcohol differed to admissions not due to alcohol being on average younger (45 vs 56 years, p<0.001) more often male (73.4% vs 45.1% males, p<0.001) and more likely to have a diagnosis synonymous with alcohol or related to recreational drug use, pancreatitis, deliberate self-harm, head injury, gastritis, suicidal ideation, upper gastrointestinal bleeds or seizures (p<0.001). An increase in admissions due to alcohol on Saturdays reflects a surge in admissions with acute alcohol intoxication above the weekly average (p=0.003). Conclusions Alcohol was thought to be implicated in 21% of emergency admissions in this cohort. CAD is responsible for a significantly greater proportion of admissions due to alcohol than acute intoxication. Interventions designed to reduce alcohol-related admissions must incorporate measures to tackle CAD. PMID:27324707

  12. Quantifying alcohol-related emergency admissions in a UK tertiary referral hospital: a cross-sectional study of chronic alcohol dependency and acute alcohol intoxication.

    PubMed

    Vardy, J; Keliher, T; Fisher, J; Ritchie, F; Bell, C; Chekroud, M; Clarey, F; Blackwood, L; Barry, L; Paton, E; Clark, A; Connelly, R

    2016-06-20

    Alcohol is responsible for a proportion of emergency admissions to hospital, with acute alcohol intoxication and chronic alcohol dependency (CAD) implicated. This study aims to quantify the proportion of hospital admissions through our emergency department (ED) which were thought by the admitting doctor to be (largely or partially) a result of alcohol consumption. ED of a UK tertiary referral hospital. All ED admissions occurring over 14 weeks from 1 September to 8 December 2012. Data obtained for 5497 of 5746 admissions (95.67%). Proportion of emergency admissions related to alcohol as defined by the admitting ED clinician. Proportion of emergency admissions due to alcohol diagnosed with acute alcohol intoxication or CAD according to ICD-10 criteria. 1152 (21.0%, 95% CI 19.9% to 22.0%) of emergency admissions were thought to be due to alcohol. 74.6% of patients admitted due to alcohol had CAD, and significantly greater than the 26.4% with 'Severe' or 'Very Severe' acute alcohol intoxication (p<0.001). Admissions due to alcohol differed to admissions not due to alcohol being on average younger (45 vs 56 years, p<0.001) more often male (73.4% vs 45.1% males, p<0.001) and more likely to have a diagnosis synonymous with alcohol or related to recreational drug use, pancreatitis, deliberate self-harm, head injury, gastritis, suicidal ideation, upper gastrointestinal bleeds or seizures (p<0.001). An increase in admissions due to alcohol on Saturdays reflects a surge in admissions with acute alcohol intoxication above the weekly average (p=0.003). Alcohol was thought to be implicated in 21% of emergency admissions in this cohort. CAD is responsible for a significantly greater proportion of admissions due to alcohol than acute intoxication. Interventions designed to reduce alcohol-related admissions must incorporate measures to tackle CAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Motor impairment: a new ethanol withdrawal phenotype in mice

    PubMed Central

    Philibin, Scott D.; Cameron, Andy J.; Metten, Pamela; Crabbe, John C.

    2015-01-01

    Alcoholism is a complex disorder with genetic and environmental risk factors. The presence of withdrawal symptoms is one criterion for alcohol dependence. Genetic animal models have followed a reductionist approach by quantifying various effects of ethanol withdrawal separately. Different ethanol withdrawal symptoms may have distinct genetic etiologies, and therefore differentiating distinct neurobiological mechanisms related to separate signs of withdrawal would increase our understanding of various aspects of the complex phenotype. This study establishes motor incoordination as a new phenotype of alcohol withdrawal in mice. Mice were made physically dependent on ethanol by exposure to ethanol vapor for 72 h. The effects of ethanol withdrawal in mice from different genetic backgrounds were measured on the accelerating rotarod, a simple motor task. Ethanol withdrawal disrupted accelerating rotarod behavior in mice. The disruptive effects of withdrawal suggest a performance rather than a learning deficit. Inbred strain comparisons suggest genetic differences in magnitude of this withdrawal phenotype. The withdrawal-induced deficits were not correlated with the selection response difference in handling convulsion severity in selectively bred Withdrawal Seizure-Prone and Withdrawal Seizure-Resistant lines. The accelerating rotarod seems to be a simple behavioral measure of ethanol withdrawal that is suitable for comparing genotypes. PMID:18690115

  14. [Causes of the people death from drunkenness and alcoholism].

    PubMed

    Erokhin, Iu A; Paukov, V S; Kirillov, Iu A

    2012-01-01

    We analyzed causes of 1008 people death, who abused by alcohol. Among them 2 groups were separated out: people died due to drunkenness and due to alcoholism. The structure of the death was similar in the both groups, however depended on alcoholism stages. The major cause of the death in group of drunkenness people was acute heart insufficiency, less commonly--lung pathology, and very rarely--brain vessels pathology and liver cirrhosis. In group of people, who died due to alcoholism, lung pathology was the major cause of these deaths, acute heart insufficiency was occurred less commonly, and very rare brain pathology because of delirium tremens or alcohol withdrawal syndrome, as so liver cirrhosis with complications. Hemorrhagic pancreonecrosis after alcoholic excess was found out in both groups, but it was more often in people, who died due to drunkenness. Obtained results show importance of chronic alcoholism identification as a disease with several stages including drunkenness and alcoholism.

  15. Differences of acute versus chronic ethanol exposure on anxiety-like behavioral responses in zebrafish.

    PubMed

    Mathur, Priya; Guo, Su

    2011-06-01

    Zebrafish, a vertebrate model organism amenable to high throughput screening, is an attractive system to model and study the mechanisms underlying human diseases. Alcoholism and alcoholic medical disorders are among the most debilitating diseases, yet the mechanisms by which ethanol inflicts the disease states are not well understood. In recent years zebrafish behavior assays have been used to study learning and memory, fear and anxiety, and social behavior. It is important to characterize the effects of ethanol on zebrafish behavioral repertoires in order to successfully harvest the strength of zebrafish for alcohol research. One prominent effect of alcohol in humans is its effect on anxiety, with acute intermediate doses relieving anxiety and withdrawal from chronic exposure increasing anxiety, both of which have significant contributions to alcohol dependence. In this study, we assess the effects of both acute and chronic ethanol exposure on anxiety-like behaviors in zebrafish, using two behavioral paradigms, the Novel Tank Diving Test and the Light/Dark Choice Assay. Acute ethanol exposure exerted significant dose-dependent anxiolytic effects. However, withdrawal from repeated intermittent ethanol exposure disabled recovery from heightened anxiety. These results demonstrate that zebrafish exhibit different anxiety-like behavioral responses to acute and chronic ethanol exposure, which are remarkably similar to these effects of alcohol in humans. Because of the accessibility of zebrafish to high throughput screening, our results suggest that genes and small molecules identified in zebrafish will be of relevance to understand how acute versus chronic alcohol exposure have opposing effects on the state of anxiety in humans. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Strain-Dependent Effects of Acute Alcohol on Synaptic Vesicle Recycling and Post-Tetanic Potentiation in Medial Glutamate Inputs to the Mouse Basolateral Amygdala.

    PubMed

    Gioia, Dominic A; McCool, Brian

    2017-04-01

    Inbred mouse strains are differentially sensitive to the acute effects of ethanol (EtOH) and are useful tools for examining how unique genomes differentially affect alcohol-related behaviors and physiology. DBA/2J mice have been shown to be sensitive to the acute anxiolytic effects of alcohol as well as the anxiogenic effects of withdrawal from chronic alcohol exposure, while B6 mice are resistant to both. Considering that the basolateral amygdala (BLA) is an important brain region for the acute and chronic effects of EtOH on fear and anxiety related behaviors, we hypothesized that there would be strain-dependent differences in the acute effects of EtOH in BLA slices. We utilized patch clamp electrophysiology in BLA coronal slices from 4 inbred mouse strains (A/J, BALBcJ, C57BL/6J, and DBA/2J) to examine how genetic background influences acute EtOH effects on synaptic vesicle recycling and post-tetanic potentiation (PTP) in response to low (2 Hz)- and high (40 Hz)-frequency stimulation. We found that EtOH inhibited synaptic vesicle recycling in a strain- and stimulation frequency-dependent manner. Vesicle recycling in DBA/2J and BALBcJ cells was inhibited by acute EtOH during both low- and high-frequency stimulation, while recycling measured from A/J cells was sensitive only during high-frequency stimulation. Recycling at C57BL/6J synapses was insensitive to EtOH regardless of stimulation frequency. We additionally found that cells from DBA/2J and BALBcJ mice were sensitive to EtOH-mediated inhibition of PTP. Acute EtOH application inhibited vesicle recycling and PTP at glutamatergic synapses in both a strain- and frequency-dependent fashion. Several presynaptic proteins that contribute to synaptic vesicle priming in addition to PTP have been implicated in alcohol-related behaviors, including Munc13, Munc18, and RIM proteins, making them potential candidates for the molecular mechanism controlling these effects. Copyright © 2017 by the Research Society on

  17. A meta-analysis of acute alcohol use and the risk of suicide attempt

    PubMed Central

    Borges, Guilherme; Bagge, Courtney; Cherpitel, Cheryl J.; Conner, Kenneth; Orozco, Ricardo; Rossow, Ingeborg

    2016-01-01

    Background While there are reviews reporting on the prevalence of acute use of alcohol (AUA) prior to suicide attempts, no review has used a meta-analytic approach to estimate common odds ratios (OR) of the effect of AUA on suicide attempts. We aim to report the results of the first meta-analysis of controlled epidemiological studies on acute alcohol use and suicide attempt. Methods The English language literature on Medline, PsychInfo, Google Scholar, and public-use databases was searched for original articles and critical review reports on acute alcohol use and suicide attempt for the period ranging from 1996–2015. Studies had to report an OR estimate for this association. Common odds ratios and 95% Confidence Intervals (95%CI) from random effects in meta-analyses for any acute alcohol use and 2 levels of alcohol use on suicide attempt were calculated. Results We gathered 7 studies that provided OR estimates for the likelihood of suicide attempt by acute alcohol use, compared to those who did not drink alcohol. Studies used case-control (3) and case-crossover design (4). All studies found increased ORs for acute alcohol use on suicide attempt. Meta-analysis revealed a common OR of 6.97 (95%CI=4.77, 10.17) for any acute alcohol use. Evidence from 4 studies suggests that «low levels of acute drinking» resulted in an OR of 2.71 (95%CI=1.56, 4.71) and «high levels» had much greater odds of suicide attempt, OR of 37.18 (95%CI=17.38, 79.53). Conclusions Acute use of alcohol is associated with increased likelihood of a suicide attempt, particularly at high doses. Such data should be incorporated into estimates of the burden of disease associated with alcohol use, which are currently limited by a consideration of only alcohol’s chronic effects. Future research should focus on the mechanisms through which acute use of alcohol confers risk for attempt. PMID:27928972

  18. Effects of alcohol on c-Myc protein in the brain

    PubMed Central

    Akinyeke, Tunde; Weber, Sydney J; Davenport, April T; Baker, Erich J; Daunais, James B; Raber, Jacob

    2018-01-01

    Alcoholism is a disorder categorized by significant impairment that is directly related to persistent and extreme use of alcohol. The effects of alcoholism on c-Myc protein expression in the brain have been scarcely studied. This is the first study to investigate the role of different characteristics of alcoholism in c-Myc protein levels in the brain. We analyzed c-Myc protein in the hypothalamus and amygdala from four different animal models of alcohol abuse. c-Myc protein was increased following alcohol exposure in acute, chronic and withdrawal models. We also observed increases in c-Myc protein exposure in animals that are genetically predisposed to alcohol and methamphetamine abuse. Lastly, c-Myc protein was increased in animals that were acutely exposed to methamphetamine when compared to control treated animals. These results suggest that in substance abuse c-Myc plays an important role in the brain’s response. PMID:27832980

  19. Effects of the NMDA receptor antagonist memantine on the expression and development of acute opiate dependence as assessed by withdrawal-potentiated startle and hyperalgesia.

    PubMed

    Harris, Andrew C; Rothwell, Patrick E; Gewirtz, Jonathan C

    2008-03-01

    While the N-methyl-D: -aspartate (NMDA) glutamate receptor has been strongly implicated in chronic opiate dependence, relatively few studies have examined the effects of NMDA receptor antagonists on withdrawal from acute opiate exposure. The current study examined the effects of memantine, a well-tolerated NMDA receptor antagonist, on acute opiate dependence as assessed by elevations in rodent startle responding (i.e., "withdrawal-potentiated startle") and increased pain sensitivity (i.e., hyperalgesia). Administration of memantine either attenuated (5 mg/kg) or blocked (10 mg/kg) the expression of withdrawal-potentiated startle during naloxone (2.5 mg/kg)-precipitated withdrawal from a single dose of morphine sulfate (10 mg/kg). Pre-treatment with the NMDA receptor antagonist also inhibited the exacerbation of withdrawal-potentiated startle across repeated acute opiate exposures. Memantine blocked the expression of acute dependence, but was less effective in inhibiting its escalation, when hyperalgesia was used as a measure of withdrawal. These doses of memantine did not affect startle responding or nociception in otherwise drug-free animals. Data from additional control groups indicated that the effects of memantine on the expression of withdrawal were not influenced by nonspecific interactions between the NMDA antagonist and either morphine or naloxone. These findings suggest that the NMDA receptor may play a key role in the earliest stages of opiate dependence and provide further evidence that memantine may be useful for the treatment of opiate withdrawal.

  20. Feasibility and reliability of the SHOT: A short scale for measuring pretreatment severity of alcohol withdrawal in the emergency department.

    PubMed

    Gray, Sara; Borgundvaag, Bjug; Sirvastava, Anita; Randall, Ian; Kahan, Meldon

    2010-10-01

    Use of a symptom-triggered scale to measure the severity of alcohol withdrawal could reduce the rate of seizures and other complications. The current standard scale, the Clinical Institute of Withdrawal Assessment (CIWA), takes a mean (±SD) of 5 minutes to complete, requiring 30 minutes of nursing time per patient when multiple measures are required. The objective was to assess the feasibility and reliability of a brief scale of alcohol withdrawal severity. The SHOT is a brief scale designed to assess alcohol withdrawal in the emergency department (ED). It includes four items: sweating, hallucinations, orientation, and tremor (SHOT). It was developed based on a literature review and a consensus process by emergency and addiction physicians. The SHOT was first piloted in one ED, and then a prospective observational study was conducted at a different ED to measure its feasibility and reliability. Subjects included patients who were in alcohol withdrawal. One nurse administered the SHOT and CIWA, and the physician repeated the SHOT independently. The SHOT was done only at baseline, before treatment was administered. In the pilot study (12 patients), the SHOT took 1 minute to complete on average, and the CIWA took 5 minutes. Sixty-one patients participated in the prospective study. For the SHOT and the CIWA done by the same nurse, the kappa was 0.88 (95% confidence interval [CI] = 0.52 to 1.0; p < 0.0001), and the Pearson's r was 0.71 (p < 0.001). The kappa for the nurse's CIWA score and the physician's SHOT score was 0.61 (95% CI = 0.25 to 0.97; p < 0.0006), and the Pearson's r was 0.48 (p = 0.002). The SHOTs performed by the nurse and physician agreed on the need for benzodiazepine treatment in 30 of 37 cases (82% agreement, kappa = 0.35, 95% CI = 0.03 to 0.67; p < 0.02). The mean (±SD) time taken by nurses and physicians to complete the SHOT was 1 (± 0.52) minute (median = 0.6 minutes). Seventeen percent of patients scored positive on the SHOT for hallucinations

  1. An integrative analysis of ethanol tolerance and withdrawal in zebrafish (Danio rerio)

    PubMed Central

    Tran, Steven; Chatterjee, Diptendu; Gerlai, Robert

    2014-01-01

    The zebrafish is emerging as a popular animal model for alcohol (ethanol or EtOH) addiction due to its simplicity and practical advantages. Two phenomena associated with ethanol addiction are the development of tolerance and withdrawal. Using a multi-level approach in the current study, we characterize ethanol tolerance and withdrawal in zebrafish. We first investigate the temporal trajectory of ethanol concentration in the zebrafish brain in response to an acute exposure and during withdrawal. We report that ethanol concentrations approach a steady state within 60 minutes of exposure to 0.50% and 1.00% v/v ethanol and rapidly decline and return to zero within 60 minutes following withdrawal from chronic ethanol exposure (0.50% v/v). We characterize the changes associated with ethanol tolerance and withdrawal in zebrafish by focusing on 3 domains relevant to ethanol addiction: motor patterns, physiological responses (i.e. cortisol levels), and neurochemical alterations. The use of multiple domains of investigation allowed an in-depth analysis of ethanol induced changes in zebrafish. PMID:24598276

  2. Outpatient alcohol withdrawal management for Aboriginal and Torres Strait Islander peoples.

    PubMed

    Brett, Jonathan; Lawrence, Leanne; Ivers, Rowena; Conigrave, Kate

    2014-08-01

    There is concern from within Aboriginal and Torres Strait Islander communities about the lack of access to alcohol withdrawal management ('detox') services. Outpatient detox is described within national Australian guidelines as a safe option for selected drinkers. However, uncertainly exists as to how suited Aboriginal and Torres Strait Islander peoples are to this approach. 
 Consultations were conducted with stakeholders of four health services providing outpatient detox for Aboriginal and Torres Strait Islander peoples in NSW. Thematic analysis was performed to determine elements perceived as important for success. Key themes that emerged were individual engagement, flexibility, assessment of suitability, Aboriginal staff and community engagement, practical support, counselling, staff education and support, coping with relapse and contingency planning. 
 There is a need to improve access to alcohol detox services for Aboriginal and Torres Strait Islander peoples. The outpatient setting seems to be a feasible and safe environment to provide this kind of service for selected drinkers.

  3. Label-Free Proteomic Analysis of Protein Changes in the Striatum during Chronic Ethanol Use and Early Withdrawal

    PubMed Central

    Ayers-Ringler, Jennifer R.; Oliveros, Alfredo; Qiu, Yanyan; Lindberg, Daniel M.; Hinton, David J.; Moore, Raymond M.; Dasari, Surendra; Choi, Doo-Sup

    2016-01-01

    The molecular mechanisms underlying the neuronal signaling changes in alcohol addiction and withdrawal are complex and multifaceted. The cortico-striatal circuit is highly implicated in these processes, and the striatum plays a significant role not only in the early stages of addiction, but in the developed-addictive state as well, including withdrawal symptoms. Transcriptional analysis is a useful method for determining changes in gene expression, however, the results do not always accurately correlate with protein levels. In this study, we employ label-free proteomic analysis to determine changes in protein expression within the striatum during chronic ethanol use and early withdrawal. The striatum, composed primarily of medium spiny GABAergic neurons, glutamatergic and dopaminergic nerve terminals and astrocytes, is relatively homogeneous for proteomic analysis. We were able to analyze more than 5000 proteins from both the dorsal (caudate and putamen) and ventral (nucleus accumbens) striatum and identified significant changes following chronic intermittent ethanol exposure and acute (8 h) withdrawal compared to ethanol naïve and ethanol exposure groups respectively. Our results showed significant changes in proteins involved in glutamate and opioid peptide signaling, and also uncovered novel pathways including mitochondrial function and lipid/cholesterol metabolism, as revealed by changes in electron transport chain proteins and RXR activation pathways. These results will be useful in the development of novel treatments for alcohol withdrawal and thereby aid in recovery from alcohol use disorder. PMID:27014007

  4. Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective.

    PubMed

    Enrico, P; Migliore, M; Spiga, S; Mulas, G; Caboni, F; Diana, M

    2016-05-13

    Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces acute and long-term changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Conceptualizing withdrawal-induced escalation of alcohol self-administration as a learned, plasticity-dependent process

    PubMed Central

    Walker, Brendan M.

    2013-01-01

    This article represents one of five contributions focusing on the topic “Plasticity and neuroadaptive responses within the extended amygdala in response to chronic or excessive alcohol exposure” that were developed by awardees participating in the Young Investigator Award Symposium at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 that was organized/chaired by Drs. Antonio Noronha and Fulton Crews and sponsored by the National Institute on Alcohol Abuse and Alcoholism. This review discusses the dependence-induced neuroadaptations in affective systems that provide a basis for negative reinforcement learning and presents evidence demonstrating that escalated alcohol consumption during withdrawal is a learned, plasticity-dependent process. The review concludes by identifying changes within extended amygdala dynorphin/kappa-opioid receptor systems that could serve as the foundation for the occurrence of negative reinforcement processes. While some evidence contained herein may be specific to alcohol dependence-related learning and plasticity, much of the information will be of relevance to any addictive disorder involving negative reinforcement mechanisms. Collectively, the information presented within this review provides a framework to assess the negative reinforcing effects of alcohol in a manner that distinguishes neuroadaptations produced by chronic alcohol exposure from the actual plasticity that is associated with negative reinforcement learning in dependent organisms. PMID:22459874

  6. Protective effect of Flos puerariae extract following acute alcohol intoxication in mice.

    PubMed

    Chen, Xiao; Cai, Fei; Guo, Shuang; Ding, Fang; He, Yi; Wu, Jiliang; Liu, Chao

    2014-07-01

    The effect of Flos Puerariae extract (FPE) on alcohol metabolism, hepatic injury, and memory impairment was assessed following acute ethanol (EtOH) intoxication in mice. The model of acute EtOH intoxication was established by intragastric administration with 8 g/kg EtOH in mice. FPE was orally administrated (gavage) once a day for 7 consecutive days. Mice were randomly divided into 4 groups: control group, model group, and FPE groups (100, 200 mg/kg). Alcohol tolerance and intoxication time, blood alcohol concentration, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in liver, aspartate amino transferase (AST) and alanine amino transferase (ALT) in serum, superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase and the formation of malondialdehyde (MDA) in both liver and brain, as well as memory ability were determined after acute alcohol exposure. Compared with model group, pretreatment with FPE significantly prolonged alcohol tolerance time and shortened intoxication time, which is accompanied by decreased blood alcohol concentration and elevated activities of ADH and ALDH in liver. Moreover, the index of hepatic injury, ALT, and AST activities in serum was markedly decreased by pretreatment with FPE. Additionally, decreased MDA level, enhanced GSH-px and catalase activities in liver, as well as enhanced SOD and catalase activities in brain were found in FPE pretreated mice after acute exposure to EtOH. Furthermore, FPE pretreated mice showed markedly relieved memory disruption following acute EtOH intoxication. This study suggests that FPE pretreatment could enhance alcohol metabolism, prevent hepatic injury, and relieve memory impairment after acute alcohol intoxication and that this effect is likely related to its modulation on the alcohol metabolizing and antioxidant enzymes. Copyright © 2014 by the Research Society on Alcoholism.

  7. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice.

    PubMed

    Blagaic, Alenka Boban; Blagaic, Vladimir; Romic, Zeljko; Sikiric, Predrag

    2004-09-24

    The stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W.1419), which was promising in inflammatory bowel disease (PL-10, PLD-116, PL-14736, Pliva) trials, protects against both acute and chronic alcohol-induced lesions in stomach and liver, but also, given peripherally, affects various centrally mediated disturbances. Now, in male NMRI mice BPC 157 (10 pg intraperitoneally, 10 ng and 10 microg, intraperitoneally or intragastrically) (i) strongly opposed acute alcohol (4 g/kg intraperitoneally) intoxication (i.e., quickly produced and sustained anesthesia, hypothermia, increased ethanol blood values, 25% fatality, 90-min assessment period) given before or after ethanol, and (ii) when given after abrupt cessation of ethanol (at 0 or 3 or 7 h withdrawal time), attenuated withdrawal (assessed through 24 hours) after 20%-alcohol drinking (7.6 g/kg) through 13 days, with provocation on the 14th day.

  8. Delirium tremens and alcohol withdrawal nationally in the Veterans Health Administration.

    PubMed

    Moore, David Thomas; Fuehrlein, Brian Scott; Rosenheck, Robert Alan

    2017-10-01

    Alcohol withdrawal-especially delirium tremens (DT)-is a potentially life-threatening condition. While short-term treatment regimens and factors that predispose to more severe symptomatology have been extensively studied, little attention has been paid to the clinical epidemiology and long-term care of the chronic medical, addictive, psychiatric, and psychosocial problems faced by these patients. National Veterans Health Administration data from fiscal year 2012 were examined to identify veterans diagnosed with DT; with withdrawal but not DT (WNDT); and with Alcohol Use Disorder (AUD) but neither DT nor WNDT. They were compared on sociodemographic characteristics, psychiatric and medical co-morbidities, and health service and psychotropic medication use, first with bivariate analyses and then multiple logistic regression. Among the 345,297 veterans diagnosed with AUD, 2,341 (0.7%) were diagnosed with DT and 6,738 (2.0%) with WNDT. Veterans diagnosed with either WNDT or DT were more likely to have been homeless, had more comorbid medical and psychiatric disorders, were more likely to be diagnosed with drug use disorders, utilized more health services, received more psychotropic medications, and were more likely to receive naltrexone. They were more likely to receive specialized legal, housing, vocational, and psychosocial rehabilitation services, as well as intensive case management. Adults with WNDT and DT suffer from multiple chronic conditions and long-term service models are needed to coordinate the work of multiple specialists and to assure continuity of care. This national study identifies sociodemographic characteristics, comorbidities, and service utilization patterns associated with WNDT and DT.(Am J Addict 2017;26:722-730). © 2017 American Academy of Addiction Psychiatry.

  9. Acute esophageal necrosis caused by alcohol abuse

    PubMed Central

    Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

    2005-01-01

    Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

  10. Purtscher-like retinopathy in acute alcoholic pancreatitis

    PubMed Central

    Nema, Nitin; Ishrat, Saba; Verma, Abha; Kela, Manoj

    2016-01-01

    A 23-year-old man with a history of alcoholism presented with vomiting, fever, and sharp epigastric pain radiating to the back and flanks. He was diagnosed as a case of acute alcoholic pancreatitis on the basis of clinical findings and investigations. On the next day of presentation, he developed sudden bilateral visual loss. His best-corrected visual acuity was finger counting at one-foot distance in both eyes. He had diffuse whitening in the circumpapillary area, haloes around the retinal vessels (Purtscher flecken) and intra-retinal hemorrhages on ophthalmoscopic examination. Optical coherence tomography revealed bilateral macular edema. These findings were characteristic of Purtscher-like retinopathy. The patient showed systemic and visual improvement at 8 weeks follow-up after receiving the conventional treatment for acute alcoholic pancreatitis. This case emphasizes the importance of fundus examination by an ophthalmologist in the diagnosis of this rare under-diagnosed entity. PMID:27433040

  11. Purtscher-like retinopathy in acute alcoholic pancreatitis.

    PubMed

    Nema, Nitin; Ishrat, Saba; Verma, Abha; Kela, Manoj

    2016-01-01

    A 23-year-old man with a history of alcoholism presented with vomiting, fever, and sharp epigastric pain radiating to the back and flanks. He was diagnosed as a case of acute alcoholic pancreatitis on the basis of clinical findings and investigations. On the next day of presentation, he developed sudden bilateral visual loss. His best-corrected visual acuity was finger counting at one-foot distance in both eyes. He had diffuse whitening in the circumpapillary area, haloes around the retinal vessels (Purtscher flecken) and intra-retinal hemorrhages on ophthalmoscopic examination. Optical coherence tomography revealed bilateral macular edema. These findings were characteristic of Purtscher-like retinopathy. The patient showed systemic and visual improvement at 8 weeks follow-up after receiving the conventional treatment for acute alcoholic pancreatitis. This case emphasizes the importance of fundus examination by an ophthalmologist in the diagnosis of this rare under-diagnosed entity.

  12. Acute Alcohol Intoxication: Differences in School Levels and Effects on Educational Performance

    ERIC Educational Resources Information Center

    Van Hoof, Joris J.; Klerk, Frouktje Ade; Van der Lely, Nicolaas

    2018-01-01

    This study examines the effects of acute alcohol intoxication on adolescents' school performance. In the 2007-2015 period, 3,317 adolescents (ages 12 to 17 years) were treated for acute alcohol intoxication, and 37 adolescents were admitted to the hospital twice. Alcohol intoxication has an overrepresentation in "low" school levels. The…

  13. Does acute alcohol intoxication cause transaminase elevations in children and adolescents?

    PubMed

    Binder, Christoph; Knibbe, Karoline; Kreissl, Alexandra; Repa, Andreas; Thanhaeuser, Margarita; Greber-Platzer, Susanne; Berger, Angelika; Jilma, Bernd; Haiden, Nadja

    2016-03-01

    Several long-term effects of alcohol abuse in children and adolescents are well described. Alcohol abuse has severe effects on neurodevelopmental outcome, such as learning disabilities, memory deficits, and decreased cognitive performance. Additionally, chronic alcohol intake is associated with chronic liver disease. However, the effects of acute alcohol intoxication on liver function in children and adolescents are not well characterized. The aim of this study was to determine if a single event of acute alcohol intoxication has short-term effects on liver function and metabolism. All children and adolescents admitted to the Department of Pediatrics and Adolescent Medicine between 2004 and 2011 with the diagnosis "acute alcohol intoxication" were included in this retrospective analysis. Clinical records were evaluated for age, gender, alcohol consumption, blood alcohol concentration, symptoms, and therapy. Blood values of the liver parameters, CK, creatinine, LDH, AP, and the values of the blood gas analysis were analyzed. During the 8-year study period, 249 children and adolescents with the diagnosis "acute alcohol intoxication" were admitted, 132 (53%) girls and 117 (47%) boys. The mean age was 15.3 ± 1.2 years and the mean blood alcohol concentration was 0.201 ± 0.049%. Girls consumed significantly less alcohol than boys (64 g vs. 90 g), but reached the same blood alcohol concentration (girls: 0.199 ± 0.049%; boys: 0.204 ± 0.049%). The mean values of liver parameters were in normal ranges, but AST was increased in 9.1%, ALT in 3.9%, and γGT in 1.4%. In contrast, the mean value of AST/ALT ratio was increased and the ratio was elevated in 92.6% of all patients. Data of the present study showed significant differences in the AST/ALT ratio (p < 0.01) in comparison to a control group. Data of the present study indicate that there might be an effect of acute alcohol intoxication on transaminase levels. The AST/ALT ratio seems to reflect the damage in hepatocytes

  14. The `One-Two Punch' of Alcoholism: Role of Central Amygdala Dynorphins / Kappa-Opioid Receptors

    PubMed Central

    Kissler, Jessica L.; Sirohi, Sunil; Reis, Daniel J.; Jansen, Heiko T.; Quock, Raymond M.; Smith, Daniel G.; Walker, Brendan M.

    2013-01-01

    Background The dynorphin (DYN)/κ-opioid receptor (KOR) system undergoes neuroadaptations following chronic alcohol exposure that promote excessive operant self-administration and negative affective-like states; however, the exact mechanisms are unknown. The present studies tested the hypothesis that an upregulated DYN/KOR system mediates excessive alcohol self-administration that occurs during withdrawal in alcohol-dependent rats by assessing DYN A peptide expression and KOR function, in combination with site-specific pharmacological manipulations. Methods Male Wistar rats were trained to self-administer alcohol using operant behavioral strategies and subjected to intermittent alcohol vapor- or air-exposure. Changes in self-administration were assessed by pharmacological challenges during acute withdrawal. In addition, 22-kHz ultrasonic vocalizations were utilized to measure negative affective-like states. Immunohistochemical techniques assessed DYN A peptide expression and [35S]GTPγS coupling assays were performed to assess KOR function. Results Alcohol-dependent rats displayed increased alcohol self-administration, negative affective-like behavior, DYN A-like immunoreactivity and KOR signaling in the amygdala compared to non-dependent controls. Site-specific infusions of a KOR antagonist selectively attenuated self-administration in dependent rats whereas, a MOR/DOR antagonist cocktail selectively reduced self-administration in non-dependent rats. A MOR antagonist/partial KOR agonist attenuated self-administration in both cohorts. Conclusion Increased DYN A and increased KOR signaling could set the stage for a `one-two punch' during withdrawal that drives excessive alcohol consumption in alcohol-dependence. Importantly, intra-CeA pharmacological challenges functionally confirmed a DYN/KOR system involvement in the escalated alcohol self-administration. Together, the DYN/KOR system is heavily dysregulated in alcohol dependence and contributes to the excessive

  15. Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal

    PubMed Central

    Reed, Brian; Ho, Ann; Kreek, Mary Jeanne

    2011-01-01

    Rationale/objectives Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin’s incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence. Methods Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals’ behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded. Results Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs. Conclusions Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior. PMID:21748254

  16. Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.

    PubMed

    Arora, Shivani; Vohora, Divya

    2016-08-01

    As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated

  17. Effects of Acute Alcohol Consumption on the Processing of Emotion in Faces: Implications for Understanding Alcohol-Related Aggression

    PubMed Central

    Attwood, Angela S.; Munafò, Marcus R.

    2016-01-01

    The negative consequences of chronic alcohol abuse are well known, but heavy episodic consumption ("binge drinking") is also associated with significant personal and societal harms. Aggressive tendencies are increased after alcohol but the mechanisms underlying these changes are not fully understood. While effects on behavioural control are likely to be important, other effects may be involved given the widespread action of alcohol. Altered processing of social signals is associated with changes in social behaviours, including aggression, but until recently there has been little research investigating the effects of acute alcohol consumption on these outcomes. Recent work investigating the effects of acute alcohol on emotional face processing has suggested reduced sensitivity to submissive signals (sad faces) and increased perceptual bias towards provocative signals (angry faces) after alcohol consumption, which may play a role in alcohol-related aggression. Here we discuss a putative mechanism that may explain how alcohol consumption influences emotional processing and subsequent aggressive responding, via disruption of OFC-amygdala connectivity. While the importance of emotional processing on social behaviours is well established, research into acute alcohol consumption and emotional processing is still in its infancy. Further research is needed and we outline a research agenda to address gaps in the literature. PMID:24920135

  18. Anxiety sensitivity and panic reactivity to bodily sensations: relation to quit-day (acute) nicotine withdrawal symptom severity among daily smokers making a self-guided quit attempt.

    PubMed

    Marshall, Erin C; Johnson, Kirsten; Bergman, Jenna; Gibson, Laura E; Zvolensky, Michael J

    2009-10-01

    The current investigation explored the main and interactive effects of panic attacks in response to laboratory-induced bodily sensations and anxiety sensitivity in predicting acute nicotine withdrawal symptoms among daily smokers making a self-guided quit attempt. Participants were 99 daily smokers (58% women; M(age) = 28.4 years, SD = 11.7) who completed a battery of questionnaires, a voluntary hyperventilation challenge, and a measure of nicotine withdrawal symptoms 12 hr after making a self-guided quit attempt. Results indicated that the interaction of anxiety sensitivity and panic responsivity to the challenge predicted quit-day nicotine withdrawal symptom severity above and beyond the main effects (p < .05). The form of the interaction indicated that the relationship between postchallenge panic attack status and acute nicotine withdrawal was more robust among individuals who were low in anxiety sensitivity. Individuals who did not experience a panic attack posthyperventilation who were also low in anxiety sensitivity reported the lowest levels of nicotine withdrawal. Results suggest that anxiety sensitivity may be less relevant with regard to acute nicotine withdrawal severity among individuals with panic-related problems.

  19. Epigenetics—Beyond the Genome in Alcoholism

    PubMed Central

    Starkman, Bela G.; Sakharkar, Amul J.; Pandey, Subhash C.

    2012-01-01

    Genetic and environmental factors play a role in the development of alcoholism. Whole-genome expression profiling has highlighted the importance of several genes that may contribute to alcohol abuse disorders. In addition, more recent findings have added yet another layer of complexity to the overall molecular mechanisms involved in a predisposition to alcoholism and addiction by demonstrating that processes related to genetic factors that do not manifest as DNA sequence changes (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure can alter gene expression levels in specific neuronal circuits that govern the behavioral consequences related to tolerance and dependence. The unremitting cycle of alcohol consumption often includes satiation and self-medication with alcohol, followed by excruciating withdrawal symptoms and the resultant relapse, which reflects both the positive and negative affective states of alcohol addiction. Recent studies have indicated that behavioral changes induced by acute and chronic ethanol exposure may involve chromatin remodeling resulting from covalent histone modifications and DNA methylation in the neuronal circuits involving a brain region called the amygdala. These findings have helped identify enzymes involved in epigenetic mechanisms, such as the histone deacetylase, histone acetyltransferase, and DNA methyltransferase enzymes, as novel therapeutic targets for the development of future pharmacotherapies for the treatment of alcoholism. PMID:23134045

  20. Epigenetics-beyond the genome in alcoholism.

    PubMed

    Starkman, Bela G; Sakharkar, Amul J; Pandey, Subhash C

    2012-01-01

    Genetic and environmental factors play a role in the development of alcoholism. Whole-genome expression profiling has highlighted the importance of several genes that may contribute to alcohol abuse disorders. In addition, more recent findings have added yet another layer of complexity to the overall molecular mechanisms involved in a predisposition to alcoholism and addiction by demonstrating that processes related to genetic factors that do not manifest as DNA sequence changes (i.e., epigenetic processes) play a role. Both acute and chronic ethanol exposure can alter gene expression levels in specific neuronal circuits that govern the behavioral consequences related to tolerance and dependence. The unremitting cycle of alcohol consumption often includes satiation and self-medication with alcohol, followed by excruciating withdrawal symptoms and the resultant relapse, which reflects both the positive and negative affective states of alcohol addiction. Recent studies have indicated that behavioral changes induced by acute and chronic ethanol exposure may involve chromatin remodeling resulting from covalent histone modifications and DNA methylation in the neuronal circuits involving a brain region called the amygdala. These findings have helped identify enzymes involved in epigenetic mechanisms, such as the histone deacetylase, histone acetyltransferase, and DNA methyltransferase enzymes, as novel therapeutic targets for the development of future pharmacotherapies for the treatment of alcoholism.

  1. Epidemiological and sociodemographic factors associated with complicated alcohol withdrawal syndrome.

    PubMed

    Monte-Secades, R; Blanco-Soto, M; Díaz-Peromingo, J A; Sanvisens-Bergé, A; Martín-González, M C; Barbosa, A; Rosón-Hernández, B; Tejero-Delgado, M A; Puerta-Louro, R; Rabuñal-Rey, R

    2017-10-01

    To analyse the influence of epidemiological and sociodemographic factors in complicated alcohol withdrawal syndrome (AWS). A multicentre, observational prospective study was conducted on consecutively added patients with AWS hospitalised in internal medicine departments. We recorded sociodemographic, epidemiological, clinical and progression data. Complicated AWS was defined as that which progressed with seizures or delirium tremens. We studied 228 episodes of AWS in 219 patients. The mean age was 54.5 years (SD, 11.5), and 90.8% were men. AWS was the cause for hospitalisation in 39.9% of the patients. Some 27.1% of the cases presented seizures, and 32.4% presented delirium tremens. The daily quantity of alcohol ingested was 17.8 standard drink units (SD, 21.4), with 16.6 years of dependence (SD, 11.3). The pattern of alcohol abuse was regular in 82.8% of the patients. Some 38.4% of the patients were married or had a partner, and 45.6% had children. Some 72.7% of the patients were unemployed or retired. Some 68.5% had only completed primary studies. Some 4.8% consumed cannabis, 5.2% consumed cocaine and 3% consumed opioids. The independent variables related to complicated AWS were consumption of a drug other than alcohol (OR, 5.3; 95% CI 1.5-18.7), low education level (OR, 3.4; 95% CI 1.6-7.3) and hospitalisation for AWS (OR, 2.9; 95% CI 1.5-5.6). The model's receiver operating characteristic area was 0.718 (95% CI 0.643-0.793). Concomitant drug abuse and a low educational level could help identify patients at risk of complicated AWS. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  2. Withdrawal strategies for outpatients

    PubMed Central

    Mezciems, Edgar

    1996-01-01

    This article discusses outpatient withdrawal strategies for patients addicted to alcohol, benzodiazepines, barbiturates, and opiates and describes some practical ways to support recovery. PMID:8828877

  3. 27 CFR 19.532 - Withdrawals of spirits for use in wine production.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use in wine production. 19.532 Section 19.532 Alcohol, Tobacco Products and Firearms ALCOHOL AND... Withdrawals Withdrawal of Spirits Without Payment of Tax § 19.532 Withdrawals of spirits for use in wine production. Wine spirits may be withdrawn to a bonded wine cellar without payment of tax for use in wine...

  4. Evidence for a causative role of N-methyl-D-aspartate receptors in an in vitro model of alcohol withdrawal hyperexcitability.

    PubMed

    Thomas, M P; Monaghan, D T; Morrisett, R A

    1998-10-01

    Synaptic mechanisms underlying hyperexcitability due to withdrawal from chronic ethanol exposure were investigated in a hippocampal explant model system using electrophysiological techniques. Whole-cell voltage clamp recordings from CA1 pyramidal cells demonstrated that acute ethanol exposure inhibited N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory postsynaptic currents by over 40%. Chronic ethanol exposure for 6 to 11 days at 35 or 75 mM induced no differences from control explants in the fast component of the population synaptic response (non-NMDAR-mediated). Prolonged field potential recordings (to 10 hr) were used to monitor the withdrawal process in vitro. Ethanol-exposed explants from both 35 and 75 mM groups displayed an increase (60% and 89%, respectively) in the NMDAR-mediated component of synaptic transmission on withdrawal from chronic exposure. Prolonged tonic-clonic electrographic seizure activity was consistently observed after ethanol withdrawal only after the increase in NMDAR function. This hyperexcitability was inhibited by the NMDAR antagonist D-2-amino-5-phosphonovaleric acid and returned once the NMDAR component was reestablished after antagonist washout. In situ hybridization studies suggest that expression of NR2B subunit mRNA may be enhanced in explants after chronic ethanol exposure. No lasting differences were observed in the NMDAR component after acute in vitro ethanol exposure and withdrawal. These data suggest that the occurance of ethanol withdrawal hyperexcitability in this system may be directly dependent on alterations in NMDAR function after chronic exposure. Since this region and others that contain ethanol sensitive NMDARs may serve as epileptic foci, long term alterations in NMDAR function may be expected to generate paroxysmal depolarizing shifts underlying ictal events after withdrawal from ethanol exposure.

  5. The Role of GABAA Receptors in the Development of Alcoholism

    PubMed Central

    Enoch, Mary-Anne

    2008-01-01

    Alcoholism is a common, heritable, chronic relapsing disorder. GABAA receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABAA receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABAA receptors: tolerance is associated with generally decreased GABAA receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABAA receptors may be implicated in the switch from heavy drinking to dependence. GABAA receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABAA receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABAA receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review. PMID:18440057

  6. Role of cortical alpha-2 adrenoceptors in alcohol withdrawal-induced depression and tricyclic antidepressants

    PubMed Central

    Getachew, Bruk; Hauser, Sheketha R.; Csoka, Antonei B.; Taylor, Robert E.; Tizabi, Yousef

    2017-01-01

    Introduction Although a role for alpha-2 adrenoceptors (alpha-2 ARs) in alcohol use disorder (AUD) and depression is suggested, very little information on a direct interaction between alcohol and these receptors is available. Methods In this study adult female Wistar and Wistar-Kyoto (WKY) rats, a putative animal model of depression, were exposed to alcohol vapor 3 h daily for 10 days (blood alcohol concentration ~150 mg%) followed by daily injection of 10 mg/kg of imipramine (IMP, a selective norepinephrine NE/serotonin reuptake inhibitor) or nomifensine (NOMI, a selective NE/dopamine reuptake inhibitor). On day 11 animals were tested for open field locomotor activity (OFLA) and forced swim test (FST) and were sacrificed 2 h later for measurement of alpha-2 ARs densities in the frontal cortex and hippocampus using [3H]RX 821002 as the specific ligand. Results Chronic alcohol treatment increased the immobility in the FST, without affecting OFLA in both Wistar and WKY rats, suggesting induction of depressive-like behavior in Wistar rats and an exacerbation of this behavior in WKY rats. Alcohol treatment also resulted in an increase in cortical but not hippocampal alpha-2 ARs densities in both Wistar and WKY rats. The behavioral effects of alcohol were completely blocked by IMP and NOMI and the neurochemical effects (increases in alpha-2 ARs) were significantly attenuated by both drugs in both strains. Conclusions The results suggest a role for cortical alpha-2 ARs in alcohol withdrawal-induced depression and that selective subtype antagonists of these receptors may be of adjunct therapeutic potential in AUD-depression co-morbidity. PMID:28414989

  7. Attenuation of Ethanol Withdrawal by Ceftriaxone-Induced Upregulation of Glutamate Transporter EAAT2

    PubMed Central

    Abulseoud, Osama A; Camsari, Ulas M; Ruby, Christina L; Kasasbeh, Aimen; Choi, Sun; Choi, Doo-Sup

    2014-01-01

    Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a 2-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 h for 3–5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 or 100 mg/kg, IP) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats vs Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg per injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS. PMID:24452391

  8. Acute alcohol intoxication in a child following ingestion of an ethyl-alcohol-based hand sanitizer.

    PubMed

    Hertzog, James H; Radwick, Allison

    2015-07-01

    While uncommon, ingestion of ethanol-based hand sanitizers by children may be associated with significant intoxication. We report the case of a 7-year-old with acute alcohol intoxication following hand sanitizer ingestion. Alcohol elimination in this patient followed zero-order kinetics with a clearance rate of 22.5 mg/kg/h, consistent with the limited pharmacokinetic information available for children who experience alcohol intoxication from more traditional sources.

  9. Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide.

    PubMed Central

    Whiting, B; Lawrence, J R; Skellern, G G; Meier, J

    1979-01-01

    1. The metabolism and plasma kinetics of chlordiazepoxide have been determined in a group of volunteers and in a group of patients with acute alcohol intoxication. 2. Using the SAAM 26 non-linear least squares fitting programme, all chlordiazepoxide plasma concentration v time data following oral administration could be analysed in terms of a one-compartment open model with metabolic conversion of chlordiazepoxide to desmethylchlordiazepoxide. 3. Acutely intoxicated patients showed a prolonged elimination of chlordiazepoxide and a reduced clearance when compared with alcohol-free volunteers. The elimination of desmethylchlordiazepoxide, on the other hand, appeared to be faster in the alcoholics. 4. Alcohol exerts significant effects on the metabolism of chlordiazepoxide in acutely intoxicated patients. PMID:760747

  10. 27 CFR 20.161 - Withdrawals under permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawals under permit. 20.161 Section 20.161 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF DENATURED ALCOHOL AND RUM Operations by Dealers and Users of Specially Denatured Spirit...

  11. Alcohol during pregnancy worsens acute respiratory infections in children.

    PubMed

    Libster, Romina; Ferolla, Fausto M; Hijano, Diego R; Acosta, Patricio L; Erviti, Anabella; Polack, Fernando P

    2015-11-01

    This study explored whether alcohol consumption during pregnancy increased the risk of life-threatening respiratory infections in children. We prospectively evaluated children under the age of two years admitted to hospitals in Buenos Aires, Argentina, with severe acute respiratory infections during the winters of 2011 and 2012. Information on maternal alcohol consumption during the third trimester of pregnancy was collected using standardised questionnaires and categorised as never, low if it was once a week and high if it was equal or more than once a week. Of the 3423 children hospitalised with acute respiratory infection, 2089 (63.7%) had respiratory syncytial virus (RSV). Alcohol consumption during the last trimester was reported by 398 mothers (12.4%) and categorised as low (n = 210, 6.5%) or high (n = 188, 5.9%). A greater effect on life-threatening respiratory infection, defined as oxygen saturation of or up to 87%, was observed with higher alcohol intake due to all viruses and specifically RSV in the logistic regression analyses. Alcohol consumption was strongly associated with life-threatening disease, particularly in boys whose adjusted odds ratio rose from 3.67 to 13.52 when their mothers drank alcohol. Alcohol consumption during pregnancy was associated with life-threatening respiratory infections in boys. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  12. Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics.

    PubMed

    Schacht, Joseph P; Anton, Raymond F; Randall, Patrick K; Li, Xingbao; Henderson, Scott; Myrick, Hugh

    2013-06-01

    Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking. However, few have combined the methodological rigor of a randomized clinical trial (RCT) with follow-up assessments to determine whether cue-elicited activation predicts relapse during treatment, the crux of alcoholism. This study analyzed functional magnetic resonance imaging (fMRI) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy. Subjects were randomized, based on their level of alcohol withdrawal (AW) at study entry, to receive either a combination of gabapentin (GBP; up to 1,200 mg for 39 days) and flumazenil (FMZ) infusions (2 days) or two placebos. Midway through the RCT, subjects were administered an fMRI alcohol cue reactivity task. There were no main effects of medication or initial AW status on cue-elicited activation, but these factors interacted, such that the GBP/FMZ/higher AW and placebo/lower AW groups, which had previously been shown to have relatively reduced drinking, demonstrated greater dorsal anterior cingulate cortex (dACC) activation to alcohol cues. Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts. Among study completers, regardless of medication or AW status, greater left dorsolateral prefrontal cortex (DLPFC) activation predicted more post-scan heavy drinking. These data suggest that alterations in task-related deactivation of dACC, a component of the default mode network, may predict better alcohol treatment response, while activation of DLPFC, an area associated with selective attention, may predict relapse drinking.

  13. The role of GABA(A) receptors in the development of alcoholism.

    PubMed

    Enoch, Mary-Anne

    2008-07-01

    Alcoholism is a common, heritable, chronic relapsing disorder. GABA(A) receptors undergo allosteric modulation by ethanol, anesthetics, benzodiazepines and neurosteroids and have been implicated in the acute as well as the chronic effects of ethanol including tolerance, dependence and withdrawal. Medications targeting GABA(A) receptors ameliorate the symptoms of acute withdrawal. Ethanol induces plasticity in GABA(A) receptors: tolerance is associated with generally decreased GABA(A) receptor activation and differentially altered subunit expression. The dopamine (DA) mesolimbic reward pathway originating in the ventral tegmental area (VTA), and interacting stress circuitry play an important role in the development of addiction. VTA GABAergic interneurons are the primary inhibitory regulators of DA neurons and a subset of VTA GABA(A) receptors may be implicated in the switch from heavy drinking to dependence. GABA(A) receptors modulate anxiety and response to stress; important elements of sustained drinking and relapse. The GABA(A) receptor subunit genes clustered on chromosome 4 are highly expressed in the reward pathway. Several recent studies have provided strong evidence that one of these genes, GABRA2, is implicated in alcoholism in humans. The influence of the interaction between ethanol and GABA(A) receptors in the reward pathway on the development of alcoholism together with genetic and epigenetic vulnerabilities will be explored in this review.

  14. Inhibitory Effects of Pretreatment with Radon on Acute Alcohol-Induced Hepatopathy in Mice

    PubMed Central

    Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

    2012-01-01

    We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m3 radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice. PMID:23213269

  15. Inhibitory effects of pretreatment with radon on acute alcohol-induced hepatopathy in mice.

    PubMed

    Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

    2012-01-01

    We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m(3) radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  16. Platelet rebound effect of alcohol withdrawal and wine drinking in rats. Relation to tannins and lipid peroxidation.

    PubMed

    Ruf, J C; Berger, J L; Renaud, S

    1995-01-01

    We investigated in rats fed a purified diet for 2 and 4 months whether wine drinking was associated with the rebound effect on thrombin-induced platelet aggregation observed after alcohol withdrawal. With 6% ethanol drinking or its equivalent in red or white wine, platelet aggregation was reduced similarly by 70% when the animals drank the alcoholic beverages up to the venipuncture. Depriving the rats of alcoholic beverages for 18 hours was associated with an increase in the platelet response of 124% in those receiving 6% ethanol, of 46% with white wine but a decrease of 59% in those with red wine. The protective effect of red wine on platelets could be reproduced by tannins (procyanidins) extracted from grape seeds or red wine and added to 6% ethanol, but not by glycerol or wine without alcohol. That was related to inhibition of the alcohol-induced lipid peroxidation as shown by the lowering of conjugated dienes, lipid peroxides, and the increase in vitamin E in plasma. Owing to tannins, the platelets of rats drinking red wine did not exhibit the rebound effect observed hours after alcohol drinking, eventually associated with sudden death and stroke in humans.

  17. Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication

    PubMed Central

    Souza-Smith, Flavia M.; Kurtz, Kristine M.; Molina, Patricia E.; Breslin, Jerome W.

    2010-01-01

    Objective Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to concious, unrestrained rats through surgically-implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results Lymphatics isolated from alcohol-intoxicated animals displayed slgnificantly decreased contraction frequency (CF) than the dextrose group, elevated stroke volume index (SVI) versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. PMID:21040117

  18. Acute alcohol response phenotype in heavy social drinkers is robust and reproducible.

    PubMed

    Roche, Daniel J O; Palmeri, Michael D; King, Andrea C

    2014-03-01

    In 3 previously published works (Brumback et al., 2007, Drug Alcohol Depend 91:10-17; King et al., 2011a, Arch Gen Psychiatry 68:389-399; Roche and King, 2010, Psychopharmacology (Berl) 212:33-44), our group characterized acute alcohol responses in a large group of young, heavy binge drinkers (n = 104) across a variety of subjective, eye-tracking, and psychometric performance measures. The primary goal of the current study was to directly replicate prior findings of alcohol response in heavy social drinkers (HD) in a second independent cohort (n = 104) using identical methodology. A secondary goal was to examine the effects of family history (FH) of alcohol use disorders (AUD) on acute alcohol response in both samples. Participants attended 2 randomized laboratory sessions in which they consumed 0.8 g/kg alcohol or a taste-masked placebo. At pre- and post-drink time points, participants completed subjective scales, psychomotor performance and eye-movement tasks, and provided salivary samples for cortisol determination. Results showed that the second cohort of heavy drinkers exhibited a nearly identical pattern of alcohol responses to the original cohort, including sensitivity to alcohol's stimulating and hedonically rewarding effects during the rising breath alcohol content (BrAC) limb, increases in sedation during the declining BrAC limb, a lack of cortisol response, and psychomotor and eye-tracking impairment that was most evident at peak BrAC. The magnitude and temporal pattern of these acute effects of alcohol in the second cohort were similar to the first cohort across all measures, with the exception of 3 eye-movement measures: pro- and antisaccade accuracy and antisaccade velocity. FH of AUD did not affect alcohol response in the first cohort, and this was replicated in the second cohort. In sum, in 2 independent samples, we have demonstrated that HD display a consistent and reliable sensitivity to alcohol's subjective effects and impairment of eye

  19. Alcohol and acute pancreatitis. An experimental study in the rat.

    PubMed

    Jalovaara, P; Apaja, M

    1978-01-01

    The effect of chronic alcohol pretreatment and various pancreatobiliary secretions on the severity of experimental pancreatitis was studied in the rat. 95 rats were pretreated with ethanol (20% w/v, 1.1 ml/100 g body weight) five times weekly for 10 to 12 weeks by gastric intubation. 88 rats served as controls. Pancreatic lesions were produced by retograde injection of different pancreatobiliary secretions into the pancreatic ducts. The secretions were collected from both normal and chronically alcohol-fed rats, and each was used for induction of experimental pancreatitis in the control and alcohol pretreated rats. Bile obtained from normal rats was no more toxic to the pancreas than 0.9% saline solution, while bile obtained from the chronically alcohol-fed rats caused significantly more serious lesions to the pancreas than did normal rat bile. Bile-pancreatic juice (mixture of secretions at papilla of Vater) of normal and chronically alcohol-fed rats was as toxic as the bile of the alcohol-fed rats. Alcohol pretreatment had no significant effect on the severity of pancreatitis when control and alcohol-fed groups separately or the whole material according to pretreatment was examined. These results suggest that the metabolic effects of ethanol on the pancreas as such do not sensitize the pancreas to acute pancreatitis. An exogenous mechanism is required. The reflux of toxic alcoholic bile into the pancreas might act as an induction factor in acute alcohol pancreatitis.

  20. 27 CFR 19.728 - Withdrawal of spirits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... premises of an alcohol fuel plant, the proprietor must render the spirits unfit for beverage use as... alcohol fuel plant premises if they will be used exclusively for fuel. (26 U.S.C. 5181, 5214) ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of spirits. 19...

  1. 27 CFR 19.996 - Withdrawal of spirits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... alcohol fuel plant, they must be rendered unfit for beverage use as provided in this subpart. Spirits rendered unfit for beverage use (fuel alcohol) may be withdrawn free of tax from plant premises exclusively... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of spirits. 19...

  2. The use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms.

    PubMed

    Jukić, Tomislav; Rojc, Bojan; Boben-Bardutzky, Darja; Hafner, Mateja; Ihan, Alojz

    2011-12-01

    We described the use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms in patients starting a detoxification therapy. Since abstinence from ethanol causes a hypodopaminergic and a hypoopioidergic environment in the reword system circuits, manifesting with withdrawal symptoms, food supplements that contains D-phenylalanine a peptidase inhibitor (of opioide inactivation) and L-amino-acids (for dopamine synthesis) were used to replenish a lack in neurotransmitters and alleviate the symptoms of alcohol withdrawal. 20 patients suffering from alcohol addictions starting a detoxification therapy have been included in a prospective, randomized, double blind study. The patients have been randomly devided in two groups. One group recieved for a period of 40 days a food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan (investigation group), and the control (placebo) group. On the first day of hospitalization the patients performed a SCL-90-R test, and blood samples were taken for measuring liver enzymes, total bilirubin, unbound cortisol and lymphocyte populations. The same was done on the 40th day of hospitalization. During the therapy a significant decrease in SCL-90-R psychiatric symptoms scores and a significant increase in CD4 lymphocyte count was observed in the investigation group. The cortisol values were significantly, but equally decreased in both groups, the same was with the liver enzymes and the total bilirubin values. We conclude that abstinence causes a major stress for the patients. The use of food supplement containing D-phenylalanine, L-glutamine and L-5-hydroxytriptophan alleviates the withdrawal symptoms and causes a rise in CD4 lymphocyte population, but it dose not affect the serum cortisol levels, which are probably more affected by liver inflammation and the liver restitution.

  3. Corticotropin-Releasing Factor (CRF) Neurocircuitry and Neuropharmacology in Alcohol Drinking.

    PubMed

    Schreiber, Allyson L; Gilpin, Nicholas W

    2018-01-28

    Alcohol use is pervasive in the United States. In the transition from nonhazardous drinking to hazardous drinking and alcohol use disorder, neuroadaptations occur within brain reward and brain stress systems. One brain signaling system that has received much attention in animal models of excessive alcohol drinking and alcohol dependence is corticotropin-releasing factor (CRF). The CRF system is composed of CRF, the urocortins, CRF-binding protein, and two receptors - CRF type 1 and CRF type 2. This review summarizes how acute, binge, and chronic alcohol dysregulates CRF signaling in hypothalamic and extra-hypothalamic brain regions and how this dysregulation may contribute to changes in alcohol reinforcement, excessive alcohol consumption, symptoms of negative affect during withdrawal, and alcohol relapse. In addition, it summarizes clinical work examining CRF type 1 receptor antagonists in humans and discusses why the brain CRF system is still relevant in alcohol research.

  4. Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

    PubMed

    Hermann, Derik; Klages, Eckard; Welzel, Helga; Mann, Karl; Croissant, Bernhard

    2005-06-01

    Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

  5. Associations Between Race, Menthol, and Acute Tobacco Withdrawal

    DTIC Science & Technology

    2013-04-13

    race differences in cessation. In the following section, the role of nicotine withdrawal as a potential mediator is examined.   7...NICOTINE ADDICTION AND WITHDRAWAL The nicotine withdrawal syndrome may potentially explain differences in cessation outcomes among African Americans...smokers,  nicotine  reduces  the  activity  of  Monoamine  Oxidase  A   and  B,  which  are   enzymes  that  break  down

  6. 27 CFR 19.585 - Production and withdrawal records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... records. 19.585 Section 19.585 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Records and Reports Production Records § 19.585 Production and withdrawal records. (a) Production of spirits. The following rules apply...

  7. 27 CFR 19.585 - Production and withdrawal records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... records. 19.585 Section 19.585 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Records and Reports Production Records § 19.585 Production and withdrawal records. (a) Production of spirits. The following rules apply...

  8. Accomplishing much in a short time: use of a rapid improvement event to redesign the assessment and treatment of patients with alcohol withdrawal.

    PubMed

    Sankoff, Jeffrey; Taub, Julie; Mintzer, David

    2013-01-01

    The use of Lean tools for quality improvement and process refinement is gaining acceptance in many health care institutions. Traditionally, these tools are used to apply incremental changes to established processes in order to reduce waste and improve quality. In this article, the authors describe a novel Lean methodology, the Rapid Improvement Event (RIE), used in a unique way to develop a new treatment protocol for a specific medical condition: alcohol withdrawal. The RIE allowed for the collaboration of a multidisciplinary group of providers invested in the success of a new protocol for alcohol withdrawal that spans areas from the emergency department to the inpatient ward at an inner-city safety net hospital. It also allowed for the definition of measures for its success once it is implemented.

  9. Prescription for antidepressant in reducing future alcohol-related readmission in patients suffering from depression and alcohol use disorder: a retrospective medical record review.

    PubMed

    Chan, Patrick; Yomen, Katie; Turcios, Jennifer; Richman, Mark

    2015-12-21

    Patients suffering from major depressive disorder are more likely to suffer from alcohol use disorder. The data is inconclusive for the effectiveness of antidepressant treatment of patients suffering from both illnesses in regards to improving sobriety and reducing alcohol-related healthcare expenses such as hospitalizations. The objective of this study is to determine if a new prescription of an antidepressant upon inpatient discharge is associated with a reduction in the number of future acute alcohol-related hospital readmissions to the same institution in patients suffering from major depressive disorder and alcohol-use disorder. A retrospective, medical record review study was conducted at a publicly-supported hospital in Sylmar, CA. A query was performed for adult patients admitted between 1/1/2005-12/31/2013 who had ICD-9 codes for both alcohol-use disorder and depression. Index admission was the first hospitalization in which the patient was currently consuming alcohol and had depression as identified by physician documentation as a problem. Acute alcohol-related admissions were those for alcohol intoxication or withdrawal (indicating current alcohol use). Patients were excluded if they were receiving an antidepressant on index admission, <18 years old, no patient data available, or not currently consuming alcohol; 139 patients met inclusion criteria. Multivariate logistical regression analysis was performed on the primary predictive variable of discharge prescription of an antidepressant along with other independent variables for alcohol readmissions: homelessness, family history of alcohol use disorder, and smoking. Discharging patients with a prescription of an antidepressant was not associated with a reduction in acute alcohol-related readmission. There was no difference in acute alcohol-related readmissions between patients discharged with (44.6 %) versus without (47.0 %) a prescription for an antidepressant (p = 0.863). The median number of days

  10. Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia.

    PubMed

    Smith, Monique L; Walcott, Andre T; Heinricher, Mary M; Ryabinin, Andrey E

    2017-01-01

    Pain is often described as a "biopsychosocial" process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another's pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in "bystanders" exposed to "primary" conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

  11. Safety of Risperidone for Acute Agitation and Alcohol Intoxication in Emergency Department Patients.

    PubMed

    Pepa, Patricia A; Lee, Kelly C; Huynh, Hien E; Wilson, Michael P

    2017-10-01

    Acute agitation in the setting of alcohol intoxication is commonly encountered in the Emergency Department (ED). In this setting, expert consensus guidelines recommend haloperidol over second-generation antipsychotics due to their limited safety data in alcohol intoxication. The primary objective was to compare vital sign changes prior to and after risperidone administration between ED patients presenting with alcohol intoxication [ETOH (+)] and without alcohol intoxication [ETOH (-)]. The secondary objective was to assess the effect of benzodiazepine co-administration with risperidone on vital signs. This was a retrospective chart review of patients who received oral risperidone for acute agitation at two university EDs between January 1, 2012 and December 31, 2015. Vital signs (oxygen saturation, systolic and diastolic blood pressure, heart rate, and respiratory rate) were compared in patients who had ingested alcohol with those who had not. There were 785 patients without evidence of alcohol intoxication who received risperidone in the ED, and 52 patients with alcohol intoxication who received risperidone. Overall, risperidone with and without alcohol intoxication and benzodiazepine administration had no statistically significant effect on vital signs (p = ns for all comparisons). This study suggests that oral risperidone may be a safe option for acute agitation in patients presenting to the ED with alcohol intoxication. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Alcohol, cardiac arrhythmias and sudden death.

    PubMed

    Kupari, M; Koskinen, P

    1998-01-01

    Studies in experimental animals have shown varying and apparently opposite effects of alcohol on cardiac rhythm and conduction. Given acutely to non-alcoholic animals, ethanol may even have anti-arrhythmic properties whereas chronic administration clearly increases the animals' susceptibility to cardiac arrhythmias. Chronic heavy alcohol use has been incriminated in the genesis of cardiac arrhythmias in humans. The evidence has come from clinical observations, retrospective case-control studies, controlled studies of consecutive admissions for arrhythmias, and prospective epidemiological investigations. Furthermore, electrophysiological studies have shown that acute alcohol administration facilitates the induction of tachyarrhythmias in selected heavy drinkers. The role of alcohol appears particularly conspicuous in idiopathic atrial fibrillation. Occasionally, ventricular tachyarrhythmias have also been provoked by alcohol intake. Several lines of evidence suggest that heavy drinking increases the risk of sudden cardiac death with fatal arrhythmia as the most likely mechanism. According to epidemiological studies this effect appears most prominent in middle-aged men and is only partly explained by confounding traits such as smoking and social class. The basic arrhythmogenic effects of alcohol are still insufficiently delineated. Subclinical heart muscle injury from chronic heavy use may be instrumental in producing patchy delays in conduction. The hyperadrenergic state of drinking and withdrawal may also contribute, as may electrolyte abnormalities, impaired vagal heart rate control, repolarization abnormalities with prolonged QT intervals and worsening of myocardial ischaemia or sleep apnoea. Most of what we know about alcohol and arrhythmias relates to heavy drinking. The effect of social drinking on clinical arrhythmias in non-alcoholic cardiac patients needs to be addressed further.

  13. Oxytocin for the treatment of drug and alcohol use disorders.

    PubMed

    Lee, Mary R; Weerts, Elise M

    2016-12-01

    There is growing interest in the use of oxytocin (OT) as a potential treatment for alcohol and other substance-use disorders. OT is a neuropeptide that modulates adaptive processes associated with addiction including reward, tolerance, associative learning, memory, and stress responses. OT exerts its effects through interactions with the hypothalamic-pituitary-adrenal axis and multiple neurotransmitter systems including the dopamine mesolimbic reward and corticotrophin-releasing factor stress systems. The effects of OT on stress systems are of high interest, given the strong link between stress, drug use and relapse, and known dysregulation of hypothalamic-pituitary-adrenal-axis activity associated with substance-use disorders. At the same time, the OT system is itself altered by acute or chronic drug exposure. This review summarizes the preclinical and clinical literature on the OT system and its relevance to drug and alcohol addiction. In addition, findings from recent clinical trials conducted in participants with cocaine, cannabis, or alcohol use disorder are included and evidence that OT may help to normalize blunted stress responses, and attenuate withdrawal-associated hypercortisolism, negative mood, and withdrawal symptoms is summarized.

  14. Acute alcohol intoxication impairs segmental body alignment in upright standing.

    PubMed

    Hafstrom, A; Patel, M; Modig, F; Magnusson, M; Fransson, P A

    2014-01-01

    Balance control when standing upright is a complex process requiring input from several partly independent mechanisms such as coordination, feedback and feedforward control, and adaptation. Acute alcohol intoxication from ethanol is recognized as a major contributor to accidental falls requiring medical care. This study aimed to investigate if intoxication at 0.06 and 0.10% blood alcohol concentration affected body alignment. Mean angular positions of the head, shoulder, hip, and knee were measured with 3D-motion analysis and compared with the ankle position in 25 healthy adults during standing with or without perturbations, and with eyes open or closed. Alcohol intoxication had significant effects on body alignment during perturbed and unperturbed stance, and on adaptation to perturbations. It induced a significantly more posterior alignment of the knees and shoulders, and a tendency for a more posterior and left deviated head alignment in perturbed stance than when sober. The impact of alcohol intoxication was most apparent on the knee alignment, where availability of visual information deteriorated the adaptation to perturbations. Thus, acute alcohol intoxication resulted in inadequate balance control strategies with increased postural rigidity and impaired adaptation to perturbations. These factors probably contribute to the increased risk of falling when intoxicated with alcohol.

  15. Alcohol disrupts sleep homeostasis.

    PubMed

    Thakkar, Mahesh M; Sharma, Rishi; Sahota, Pradeep

    2015-06-01

    Alcohol is a potent somnogen and one of the most commonly used "over the counter" sleep aids. In healthy non-alcoholics, acute alcohol decreases sleep latency, consolidates and increases the quality (delta power) and quantity of NREM sleep during the first half of the night. However, sleep is disrupted during the second half. Alcoholics, both during drinking periods and during abstinences, suffer from a multitude of sleep disruptions manifested by profound insomnia, excessive daytime sleepiness, and altered sleep architecture. Furthermore, subjective and objective indicators of sleep disturbances are predictors of relapse. Finally, within the USA, it is estimated that societal costs of alcohol-related sleep disorders exceeds $18 billion. Thus, although alcohol-associated sleep problems have significant economic and clinical consequences, very little is known about how and where alcohol acts to affect sleep. In this review, we have described our attempts to unravel the mechanism of alcohol-induced sleep disruptions. We have conducted a series of experiments using two different species, rats and mice, as animal models. We performed microdialysis, immunohistochemical, pharmacological, sleep deprivation and lesion studies which suggest that the sleep-promoting effects of alcohol may be mediated via alcohol's action on the mediators of sleep homeostasis: adenosine (AD) and the wake-promoting cholinergic neurons of the basal forebrain (BF). Alcohol, via its action on AD uptake, increases extracellular AD resulting in the inhibition of BF wake-promoting neurons. Since binge alcohol consumption is a highly prevalent pattern of alcohol consumption and disrupts sleep, we examined the effects of binge drinking on sleep-wakefulness. Our results suggest that disrupted sleep homeostasis may be the primary cause of sleep disruption observed following binge drinking. Finally, we have also shown that sleep disruptions observed during acute withdrawal, are caused due to impaired

  16. Prior social experience affects the behavioral and neural responses to acute alcohol in juvenile crayfish.

    PubMed

    Swierzbinski, Matthew E; Lazarchik, Andrew R; Herberholz, Jens

    2017-04-15

    The effects of alcohol on society can be devastating, both as an immediate consequence of acute intoxication and as a powerful drug of abuse. However, the neurocellular mechanisms of alcohol intoxication are still elusive, partly because of the complex interactions between alcohol and nervous system function. We found that juvenile crayfish are behaviorally sensitive to acute alcohol exposure and progress through stages that are strikingly similar to those of most other intoxicated organisms. Most surprisingly, we found that the social history of the animals significantly modified the acute effects of alcohol. Crayfish taken from a rich social environment became intoxicated more rapidly than animals that were socially isolated before alcohol exposure. In addition, we found that the modulation of intoxicated behaviors by prior social experience was paralleled on the level of individual neurons. These results significantly improve our understanding of the mechanisms underlying the interplay between social experience, alcohol intoxication and nervous system function. © 2017. Published by The Company of Biologists Ltd.

  17. Targeting Dynorphin/Kappa Opioid Receptor Systems to Treat Alcohol Abuse and Dependence

    PubMed Central

    Walker, Brendan M.; Valdez, Glenn R.; McLaughlin, Jay P.; Bakalkin, Georgy

    2012-01-01

    This review represents the focus of a symposium that was presented at the “Alcoholism and Stress: A Framework for Future Treatment Strategies” conference in Volterra, Italy on May 3–6, 2011 and organized / chaired by Dr. Brendan M. Walker. The primary goal of the symposium was to evaluate and disseminate contemporary findings regarding the emerging role of kappa-opioid receptors (KORs) and their endogenous ligands dynorphins (DYNs) in the regulation of escalated alcohol consumption, negative affect and cognitive dysfunction associated with alcohol dependence, as well as DYN / KOR mediation of the effects of chronic stress on alcohol reward and seeking behaviors. Dr. Glenn Valdez described a role for KORs in the anxiogenic effects of alcohol withdrawal. Dr. Jay McLaughlin focused on the role of KORs in repeated stress-induced potentiation of alcohol reward and increased alcohol consumption. Dr. Brendan Walker presented data characterizing the effects of KOR antagonism within the extended amygdala on withdrawal-induced escalation of alcohol self-administration in dependent animals. Dr. Georgy Bakalkin concluded with data indicative of altered DYNs and KORs in the prefrontal cortex of alcohol dependent humans that could underlie diminished cognitive performance. Collectively, the data presented within this symposium identified the multifaceted contribution of KORs to the characteristics of acute and chronic alcohol-induced behavioral dysregulation and provided a foundation for the development of pharmacotherapeutic strategies to treat certain aspects of alcohol use disorders. PMID:22459870

  18. [Effect of puerarin in myocardial protection in rats with acute and chronic alcoholism].

    PubMed

    Cui, Shu-qin

    2011-12-01

    To investigate the protective effect of puerarin on the myocardium of rats with acute and chronic alcoholism. In acute alcoholism experiment, normal male SD rats were randomly divided into the control group, alcoholism group and puerarin group (n=8), and high- and low-dose puerarin was administered. In chronic alcoholism experiment, increasing puerarin doses were given. Serum and myocardial levels of spartate aminotransferase (AST) and creatine phosphokinase (CPK) were determined using enzymatic methed, and superoxide dismutase (SOD), malondialdehyde (MDA), Ca(2+)-Mg(2+)-ATPase, and Na(+)-K(+)-ATPase in the myocardium were assayed with colorimetric method. HE staining was used to observe the microscopic changes of the myocardium. Compared with alcoholism group, puerarin-treated groups showed significantly lowered myocardial contents of MDA, CPK and AST and serum levels of AST and CPK (P<0.05, P<0.01) and increased myocardial SOD (P<0.05, P<0.01), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activity (P<0.05, P<0.01), but Na(+)-K(+)-ATPase was similar between the two groups (P>0.05). HE staining of the myocardium showed cell swelling and obscure cell boundaries in alcoholism group, especially in chronic alcoholism group. The myocardial structure in puerarin group remained clear and regular. Puerarin can protect from myocardial injuries induced by acute and chronic alcoholism in rats.

  19. Acute exercise effects on smoking withdrawal symptoms and desire to smoke are not related to expectation.

    PubMed

    Daniel, James Z; Cropley, Mark; Fife-Schaw, Chris

    2007-11-01

    Recent research has shown that 10 min of moderate intensity exercise reduce smoking withdrawal symptoms and desire to smoke in acutely abstinent smokers. The aim of the current study was to determine whether the reductions are related to participant expectation of these effects. Forty-five sedentary participants who had smoked ten or more cigarettes per day for at least 3 years reported their expectation of the effects of exercise on smoking withdrawal symptoms. Approximately 1 month later, participants were randomly assigned to one of three groups after 11-15 h of overnight smoking abstinence. Each group read either a positive, negative or neutral statement concerning exercise effects on smoking withdrawal symptoms. They rated their expectation again and then completed 10 min of moderate intensity exercise on a stationary bicycle ergometer. Using standardised scales, participants rated smoking withdrawal symptoms and desire to smoke at 10, 5 and 0 min before exercise, then at 5 and 10 min during exercise and 15 and 20 min post-exercise. Expectation of exercise effects on withdrawal were manipulated in the predicted directions. No significant group main effects were found for any symptom. Significant reductions in symptoms and desire to smoke occurred during and after exercise regardless of participant expectation. Ten minutes of moderate intensity exercise can lead to reductions in desire to smoke and smoking withdrawal symptoms, which are not due to the participant's expectation of exercise effects. These findings support the use of short periods of exercise as an aid to smoking cessation.

  20. Circadian wheel-running activity during withdrawal from chronic intermittent ethanol exposure in mice

    PubMed Central

    Logan, Ryan W.; Seggio, Joseph A.; Robinson, Stacy L.; Richard, Gregory R.; Rosenwasser, Alan M.

    2010-01-01

    Alcohol withdrawal is associated with affective-behavioral disturbances in both human alcoholics and in animal models. In general, these phenomena are potentiated by increased alcohol exposure duration and by prior withdrawal episodes. Previous studies have also reported locomotor hypoactivity during ethanol withdrawal in rats and mice, but only in novel test environments, not in the home-cage. In the present study, we examined the effects of withdrawal from chronic intermittent ethanol (CIE) vapor exposure on the level and circadian periodicity of wheel-running activity in C57BL/6J mice. CIE treatment resulted in reductions in wheel-running activity relative to plain-air controls that persisted for about one week after withdrawal. Analysis of circadian waveforms indicated that reduced activity occurred throughout the night phase, but that daily activity patterns were otherwise unaltered. CIE failed to alter free-running circadian period or phase in animals maintained under constant darkness. These results show that ethanol withdrawal can result in locomotor hypoactivity even in the habitual, home-cage environment, and suggest that withdrawal-related reductions in wheel-running activity may reflect the specific motivational significance of this behavior. PMID:20682191

  1. Acute alcohol effects on facial expressions of emotions in social drinkers: a systematic review

    PubMed Central

    Capito, Eva Susanne; Lautenbacher, Stefan; Horn-Hofmann, Claudia

    2017-01-01

    Background As known from everyday experience and experimental research, alcohol modulates emotions. Particularly regarding social interaction, the effects of alcohol on the facial expression of emotion might be of relevance. However, these effects have not been systematically studied. We performed a systematic review on acute alcohol effects on social drinkers’ facial expressions of induced positive and negative emotions. Materials and methods With a predefined algorithm, we searched three electronic databases (PubMed, PsycInfo, and Web of Science) for studies conducted on social drinkers that used acute alcohol administration, emotion induction, and standardized methods to record facial expressions. We excluded those studies that failed common quality standards, and finally selected 13 investigations for this review. Results Overall, alcohol exerted effects on facial expressions of emotions in social drinkers. These effects were not generally disinhibiting, but varied depending on the valence of emotion and on social interaction. Being consumed within social groups, alcohol mostly influenced facial expressions of emotions in a socially desirable way, thus underscoring the view of alcohol as social lubricant. However, methodical differences regarding alcohol administration between the studies complicated comparability. Conclusion Our review highlighted the relevance of emotional valence and social-context factors for acute alcohol effects on social drinkers’ facial expressions of emotions. Future research should investigate how these alcohol effects influence the development of problematic drinking behavior in social drinkers. PMID:29255375

  2. Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study

    PubMed Central

    Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

    2017-01-01

    Background Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Methods Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Results Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Conclusions Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under

  3. Influence of Volatile Anesthesia on the Release of Glutamate and other Amino Acids in the Nucleus Accumbens in a Rat Model of Alcohol Withdrawal: A Pilot Study.

    PubMed

    Seidemann, Thomas; Spies, Claudia; Morgenstern, Rudolf; Wernecke, Klaus-Dieter; Netzhammer, Nicolai

    2017-01-01

    Alcohol withdrawal syndrome is a potentially life-threatening condition, which can occur when patients with alcohol use disorders undergo general anesthesia. Excitatory amino acids, such as glutamate, act as neurotransmitters and are known to play a key role in alcohol withdrawal syndrome. To understand this process better, we investigated the influence of isoflurane, sevoflurane, and desflurane anesthesia on the profile of excitatory and inhibitory amino acids in the nucleus accumbens (NAcc) of alcohol-withdrawn rats (AWR). Eighty Wistar rats were randomized into two groups of 40, pair-fed with alcoholic or non-alcoholic nutrition. Nutrition was withdrawn and microdialysis was performed to measure the activity of amino acids in the NAcc. The onset time of the withdrawal syndrome was first determined in an experiment with 20 rats. Sixty rats then received isoflurane, sevoflurane, or desflurane anesthesia for three hours during the withdrawal period, followed by one hour of elimination. Amino acid concentrations were measured using chromatography and results were compared to baseline levels measured prior to induction of anesthesia. Glutamate release increased in the alcohol group at five hours after the last alcohol intake (p = 0.002). After 140 min, desflurane anesthesia led to a lower release of glutamate (p < 0.001) and aspartate (p = 0.0007) in AWR compared to controls. GABA release under and after desflurane anesthesia was also significantly lower in AWR than controls (p = 0.023). Over the course of isoflurane anesthesia, arginine release decreased in AWR compared to controls (p < 0.001), and aspartate release increased after induction relative to controls (p20min = 0.015 and p40min = 0.006). However, amino acid levels did not differ between the groups as a result of sevoflurane anesthesia. Each of three volatile anesthetics we studied showed different effects on excitatory and inhibitory amino acid concentrations. Under desflurane anesthesia, both glutamate

  4. Behavioral economic analysis of stress effects on acute motivation for alcohol.

    PubMed

    Owens, Max M; Ray, Lara A; MacKillop, James

    2015-01-01

    Due to issues of definition and measurement, the heavy emphasis on subjective craving in the measurement of acute motivation for alcohol and other drugs remains controversial. Behavioral economic approaches have increasingly been applied to better understand acute drug motivation, particularly using demand curve modeling via purchase tasks to characterize the perceived reinforcing value of the drug. This approach has focused on using putatively more objective indices of motivation, such as units of consumption, monetary expenditure, and price sensitivity. To extend this line of research, the current study used an alcohol purchase task to determine if, compared to a neutral induction, a personalized stress induction would increase alcohol demand in a sample of heavy drinkers. The stress induction significantly increased multiple measures of the reinforcing value of alcohol to the individual, including consumption at zero price (intensity), the maximum total amount of money spent on alcohol (Omax), the first price where consumption was reduced to zero (breakpoint), and the general responsiveness of consumption to increases in price (elasticity). These measures correlated only modestly with craving and mood. Self-reported income was largely unrelated to demand but moderated the influence of stress on Omax. Moderation based on CRH-BP genotype (rs10055255) was present for Omax, with T allele homozygotes exhibiting more pronounced increases in response to stress. These results provide further support for a behavioral economic approach to measuring acute drug motivation. The findings also highlight the potential relevance of income and genetic factors in understanding state effects on the perceived reinforcing value of alcohol. © Society for the Experimental Analysis of Behavior.

  5. [Metabolic disturbances and ways of their pharmacological correction in acute poisoning with ethanol in patients with chronic alcoholism].

    PubMed

    Livanov, G A; Lodyagin, A N; Lubsanova, S V; Kovalenko, A L; Batotsyrenov, B V; Sergeev, O A; Loladze, A T; Andrianov, A Yu

    2015-01-01

    To study an influence of chronic alcoholism on the clinical course and severity of metabolic disturbances in patients with acute poisoning with ethanol and to improve the treatment. Authors examined 93 patients stratified into three groups (acute poisoning with ethanol in patients with chronic alcoholism, without chronic alcoholism and those treated with reamberin). The presence of chronic alcoholism significantly augmented metabolic disturbances and influenced the disturbance of oxygen-transport function and free-radical processes in patients with acute intoxication with ethanol. Using of reamberin in the complex intensive therapy led to the decrease in metabolic disorders, which improved the clinical course of acute poisoning with ethanol in patients with chronic alcoholism.

  6. Acute and chronic alcohol use correlated with methods of suicide in a Swiss national sample.

    PubMed

    Pfeifer, P; Bartsch, C; Hemmer, A; Reisch, T

    2017-09-01

    Chronic and acute alcohol use are highly associated risk factors for suicides worldwide. Therefore, we examined suicide cases with and without alcohol use disorder (AUD) using data from the SNSF project "Suicide in Switzerland: A detailed national survey". Our investigations focus on correlations between acute and chronic alcohol use with reference to suicide and potential interactions with the methods of suicide. We used data from the SNSF project in which all cases of registered completed suicide in Switzerland reported to any of the seven Swiss institutes of legal and forensic medicine between 2000 and 2010 were collected. We extracted cases that were tested for blood alcohol to use in our analysis. We compared clinical characteristics, blood alcohol concentrations, and methods of suicide in cases with and without AUD. Out of 6497 cases, 2946 subjects were tested for acute alcohol use and included in our analysis. Of the latter, 366 (12.4%) persons had a medical history of AUD. Subjects with AUD significantly had higher blood alcohol concentrations and were more often in medical treatment before suicide. Drug intoxication as method of suicide was more frequent in cases with AUD compared to NAUD. Overall, we found a high incidence of acute alcohol use at the time of death in chronic alcohol misusers (AUD). The five methods of suicide most commonly used in Switzerland differed considerably between individuals with and without AUD. Blood alcohol concentrations varied across different methods of suicide independently from the medical history in both groups. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Critical thoughts on current rodent models for evaluating potential treatments of alcohol addiction and withdrawal

    PubMed Central

    Ripley, Tamzin L; Stephens, David N

    2011-01-01

    Despite years of neurobiological research that have helped to identify potential therapeutic targets, we do not have a reliable pharmacological treatment for alcoholism. There are a range of possible explanations for this failure, including arguments that alcoholism is a spectrum disorder and that different population subtypes may respond to different treatments. This view is supported by categorisations such as early- and late-onset alcoholism, whilst multifactorial genetic factors may also alter responsivity to pharmacological agents. Furthermore, experience of alcohol withdrawal may play a role in future drinking in a way that may distinguish alcoholism from other forms of addiction. Additionally, our neurobiological models, based largely upon results from rodent studies, may not mimic specific aspects of the human condition and may reflect different underlying phenomena and biological processes from the clinical pattern. As a result, potential treatments may be targeting inappropriate aspects of alcohol-related behaviours. Instead, we suggest a more profitable approach is (a) to identify well-defined intermediate behavioural phenotypes in human experimental models that reflect defined aspects of the human clinical disorder and (b) to develop animal models that are homologous with those phenotypes in terms of psychological processes and underlying neurobiological mechanisms. This review describes an array of animal models currently used in the addiction field and what they tell us about alcoholism. We will then examine how established pharmacological agents have been developed using only a limited number of these models, before describing some alternative novel approaches to achieving homology between animal and human experimental measures. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21470204

  8. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  9. [Characteristics of alcohol withdrawal delirium in surgical patients and recommendations for treatment].

    PubMed

    Naber, M; Franz, W; Overbeck, W

    1991-02-01

    An alcohol withdrawal syndrome affects the patient in a 'vulnerable phase' either after an operation or posttraumatically. It can be shown pathophysiologically, that the symptoms are caused by a hyperactivity of the central sympathetic nervous system and a disbalance of the neurotransmitters. As for these complex symptoms, a multi-layered treatment is required. We report on our experiences with 23 patients who were treated in our intensive care unit. The treatment included a benzo-diazepine and a drug effecting central alpha 2-receptors. Only three of these patients had to be intubated or ventilated. Because of the induced bradycardia monitor observation was required in all cases. The patients could be wakened up at any time and thus were co-operative for basic care. One patient died of pulmonary embolism, a second patient died of cardiovascular failure as a consequence of cardiac insufficiency.

  10. The effects of acute alcohol intoxication on the cognitive mechanisms underlying false facial recognition.

    PubMed

    Colloff, Melissa F; Flowe, Heather D

    2016-06-01

    False face recognition rates are sometimes higher when faces are learned while under the influence of alcohol. Alcohol myopia theory (AMT) proposes that acute alcohol intoxication during face learning causes people to attend to only the most salient features of a face, impairing the encoding of less salient facial features. Yet, there is currently no direct evidence to support this claim. Our objective was to test whether acute alcohol intoxication impairs face learning by causing subjects to attend to a salient (i.e., distinctive) facial feature over other facial features, as per AMT. We employed a balanced placebo design (N = 100). Subjects in the alcohol group were dosed to achieve a blood alcohol concentration (BAC) of 0.06 %, whereas the no alcohol group consumed tonic water. Alcohol expectancy was controlled. Subjects studied faces with or without a distinctive feature (e.g., scar, piercing). An old-new recognition test followed. Some of the test faces were "old" (i.e., previously studied), and some were "new" (i.e., not previously studied). We varied whether the new test faces had a previously studied distinctive feature versus other familiar characteristics. Intoxicated and sober recognition accuracy was comparable, but subjects in the alcohol group made more positive identifications overall compared to the no alcohol group. The results are not in keeping with AMT. Rather, a more general cognitive mechanism appears to underlie false face recognition in intoxicated subjects. Specifically, acute alcohol intoxication during face learning results in more liberal choosing, perhaps because of an increased reliance on familiarity.

  11. The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) in the assessment of alcohol use disorders among acute injury patients.

    PubMed

    Wade, Darryl; Varker, Tracey; Forbes, David; O'Donnell, Meaghan

    2014-01-01

    The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) is a brief alcohol screening test and a candidate for inclusion in recommended screening and brief intervention protocols for acute injury patients. The objective of the current study was to examine the performance of the AUDIT-C to risk stratify injury patients with regard to their probability of having an alcohol use disorder. Participants (n = 1,004) were from a multisite Australian acute injury study. Stratum-specific likelihood ratio (SSLR) analysis was used to examine the performance of previously recommended AUDIT-C risk zones based on a dichotomous cut-point (0 to 3, 4 to 12) and risk zones derived from SSLR analysis to estimate the probability of a current alcohol use disorder. Almost a quarter (23%) of patients met criteria for a current alcohol use disorder. SSLR analysis identified multiple AUDIT-C risk zones (0 to 3, 4 to 5, 6, 7 to 8, 9 to 12) with a wide range of posttest probabilities of alcohol use disorder, from 5 to 68%. The area under receiver operating characteristic curve (AUROC) score was 0.82 for the derived AUDIT-C zones and 0.70 for the recommended AUDIT-C zones. A comparison between AUROCs revealed that overall the derived zones performed significantly better than the recommended zones in being able to discriminate between patients with and without alcohol use disorder. The findings of SSLR analysis can be used to improve estimates of the probability of alcohol use disorder in acute injury patients based on AUDIT-C scores. In turn, this information can inform clinical interventions and the development of screening and intervention protocols in a range of settings. Copyright © 2013 by the Research Society on Alcoholism.

  12. 27 CFR 19.585 - Production and withdrawal records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... records. 19.585 Section 19.585 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Records and Reports Production Records § 19.585 Production and withdrawal records. (a) Production of spirits. The following rules apply...

  13. 27 CFR 22.111 - Withdrawals under permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF THE TREASURY LIQUORS DISTRIBUTION AND USE OF TAX-FREE ALCOHOL Withdrawal and Receipt of Tax... distilled spirits plant or, under the provisions of 26 U.S.C. 5688(a)(2)(B), receive alcohol from the... its permit, or amended permit, to a distilled spirits plant for the “initial order” from that...

  14. Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.

    PubMed

    Gispert, Juan D; Figueiras, Francisca P; Vengeliene, Valentina; Herance, José R; Rojas, Santiago; Spanagel, Rainer

    2017-06-01

    Several [ 18 F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [ 18 F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [ 18 F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [ 18 F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. MDMA attenuates THC withdrawal syndrome in mice.

    PubMed

    Touriño, Clara; Maldonado, Rafael; Valverde, Olga

    2007-07-01

    3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition, and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet. In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Delta(9)-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration. Both chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA. The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.

  16. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers.

    PubMed

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-03-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose-response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug-response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  17. Acute alcohol effects on explicit and implicit motivation to drink alcohol in socially drinking adolescents.

    PubMed

    Jünger, Elisabeth; Javadi, Amir-Homayoun; Wiers, Corinde E; Sommer, Christian; Garbusow, Maria; Bernhardt, Nadine; Kuitunen-Paul, Sören; Smolka, Michael N; Zimmermann, Ulrich S

    2017-07-01

    Alcohol-related cues can evoke explicit and implicit motivation to drink alcohol. Concerning the links between explicit and implicit motivation, there are mixed findings. Therefore, we investigated both concepts in 51 healthy 18- to 19-year-old males, who are less affected by neuropsychological deficits in decision-making that are attributed to previous alcohol exposure than older participants. In a randomized crossover design, adolescents were infused with either alcohol or placebo. Self-ratings of alcohol desire, thirst, well-being and alcohol effects comprised our explicit measures of motivation. To measure implicit motivation, we used money and drink stimuli in a Pavlovian conditioning (Pc) task and an Approach-Avoidance Task (AAT). Alcohol administration increased explicit motivation to drink alcohol, reduced Pc choices of alcoholic drink-conditioned stimuli, but had no effect on the AAT. This combination of results might be explained by differences between goal-directed and habitual behavior or a temporary reduction in rewarding outcome expectancies. Further, there was no association between our measures of motivation to drink alcohol, indicating that both self-reported motivation to drink and implicit approach tendencies may independently contribute to adolescents' actual alcohol intake. Correlations between Alcohol Use Disorders Identification Test (AUDIT) scores and our measures of motivation to drink alcohol suggest that interventions should target high-risk adolescents after alcohol intake. Clinical trials: Project 4: Acute Effects of Alcohol on Learning and Habitization in Healthy Young Adults (LeAD_P4); NCT01858818; https://clinicaltrials.gov/ct2/show/NCT01858818.

  18. IV crystalloid fluid for acute alcoholic intoxication prolongs ED length of stay.

    PubMed

    Homma, Yosuke; Shiga, Takashi; Hoshina, Yuiko; Numata, Kenji; Mizobe, Michiko; Nakashima, Yoshiyuki; Takahashi, Jin; Inoue, Tetsuya; Takahashi, Osamu; Funakoshi, Hiraku

    2018-04-01

    Acute alcohol intoxication is often treated in emergency departments by intravenous crystalloid fluid (IVF), but it is not clear that this shortens the time to achieving sobriety. The study aim was to investigate the association of IVF infusion and length of stay in the ED. This single-center retrospective cohort study was conducted in Japan and included patients aged ≥20years of age and treated for acute alcohol intoxication without or with IVF. The primary outcome was the length of the ED stay and the treatments were compared by time-to-event analysis. A total of 106 patients, 42 treated without IVF and 64 with IVF. The baseline characteristics of the two groups were similar. Kaplan-Meier analysis and the generalized Wilcoxon test found no significant difference between the two treatments in the time to ED discharge. The median time was 189 (IQR 160-230) minutes without IVF and 254.5 (203-267 minutes with IVF; p=0.052). A Cox proportional hazards regression model adjusted for potential confounding variables found that patients treated with IVF were less likely to be discharged earlier than those treated without IVF (HR 0.54, 95% CI: 0.35-0.84, p=0.006). IVF for treatment of acute alcoholic intoxication prolonged ED length of stay even after adjustment for potential confounders. Patients given IVF for acute alcohol intoxication should be selected with care. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Age-Dependent Effects of Acute Alcohol Administration in the Hippocampal Phosphoproteome.

    PubMed

    Contreras, Ana; Morales, Lidia; Tebourbi, Ali; Miguéns, Miguel; Olmo, Nuria Del; Pérez-García, Carmen

    2017-12-18

    Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration. We have compared the phosphoprotein expression in the hippocampus of adult and adolescent Wistar rats treated with a single dose of ethanol (5 g/kg i.p.), using a proteomic approach including phosphoprotein enrichment by immobilized metal affinity chromatography (IMAC). Our proteomic analysis revealed that 13 proteins were differentially affected by age, ethanol administration, or both. Most of these proteins are involved in neuroprotection and are expressed less in young rats treated with ethanol. We conclude that acute alcohol induces important changes in the expression of phosphoproteins in the hippocampus that could increase the risk of neurodegenerative disorders, especially when the alcohol exposure begins in adolescence.

  20. Identification of a QTL in Mus musculus for Alcohol Preference, Withdrawal, and Ap3m2 Expression Using Integrative Functional Genomics and Precision Genetics

    PubMed Central

    Bubier, Jason A.; Jay, Jeremy J.; Baker, Christopher L.; Bergeson, Susan E.; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C.; Chesler, Elissa J.

    2014-01-01

    Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits. PMID:24923803

  1. Acute effects of a guided relaxation routine (body scan) on tobacco withdrawal symptoms and cravings in abstinent smokers.

    PubMed

    Cropley, Mark; Ussher, Michael; Charitou, Elli

    2007-06-01

    To examine the acute effects of a guided relaxation routine (body scan) on desire to smoke and tobacco withdrawal symptoms in overnight abstinent smokers. Experimental. Thirty individuals reporting to smoke 10 or more cigarettes daily for at least 3 years. Participants were assigned randomly to complete a 10-minute body scan (experimental group n = 15) or listen to a natural history passage for 10 minutes (control group n = 15). Ratings of strength of desire to smoke and smoking withdrawal symptoms were assessed at baseline, immediately after the interventions, and 5, 10 and 15 minutes post-intervention. There was a significant group x time interaction for strength of desire to smoke. The mean desire to smoke rating was significantly lower in the body scan group relative to the control group immediately after the intervention, and 5 minutes post-intervention. The body scan group also reported lower ratings of irritability, tension and restlessness, relative to the controls. A brief body scan intervention reduces strength of desire to smoke and some tobacco withdrawal symptoms in temporarily abstaining smokers. The body scan may be beneficial as a technique for managing cigarette cravings and withdrawal.

  2. Acute Morphine, Chronic Morphine, and Morphine Withdrawal Differently Affect Pleiotrophin, Midkine, and Receptor Protein Tyrosine Phosphatase β/ζ Regulation in the Ventral Tegmental Area.

    PubMed

    García-Pérez, Daniel; Laorden, M Luisa; Milanés, M Victoria

    2017-01-01

    Pleiotrophin (PTN) and midkine (MK) are secreted growth factors and cytokines, proposed to be significant neuromodulators with multiple neuronal functions. PTN and MK are generally related with cell proliferation, growth, and differentiation by acting through different receptors. PTN or MK, signaling through receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ), lead to the activation of extracellular signal-regulated kinases (ERKs) and thymoma viral proto-oncogene (Akt), which induce morphological changes and modulate addictive behaviors. Besides, there is increasing evidence that during the development of drug addiction, astrocytes contribute to the synaptic plasticity by synthesizing and releasing substances such as cytokines. In the present work, we studied the effect of acute morphine, chronic morphine, and morphine withdrawal on PTN, MK, and RPTPβ/ζ expression and on their signaling pathways in the ventral tegmental area (VTA). Present results indicated that PTN, MK, and RPTPβ/ζ levels increased after acute morphine injection, returned to basal levels during chronic opioid treatment, and were upregulated again during morphine withdrawal. We also observed an activation of astrocytes after acute morphine injection and during opiate dependence and withdrawal. In addition, immunofluorescence analysis revealed that PTN, but not MK, was overexpressed in astrocytes and that dopaminergic neurons expressed RPTPβ/ζ. Interestingly, p-ERK 1/2 levels during chronic morphine and morphine withdrawal correlated RPTPβ/ζ expression. All these observations suggest that the neuroprotective and behavioral adaptations that occur during opiate addiction could be, at least partly, mediated by these cytokines.

  3. [Relationship between the Expression of α-syn and Neuronal Apoptosis in Brain Cortex of Acute Alcoholism Rats].

    PubMed

    Li, F; Zhang, Y; Ma, S L

    2016-12-01

    To observe the changes of expression of α-synuclein (α-syn) and neuronal apoptosis in brain cortex of acute alcoholism rats and to explore the mechanism of the damage caused by ethanol to the neurons. The model of acute alcoholism rat was established by 50% alcohol gavage. The α-syn and caspase-3 were detected by immunohistochemical staining and imaging analysis at 1 h, 3 h, 6 h and 12 h after acute alcoholism. The number of positive cell and mean of optical density were detected and the trend change was analyzed. The variance analysis and t -test were also performed. The number of α-syn positive cell and average optical density in brain cortex of acute alcoholism rat increased significantly and peaked at 6 hour with a following slight decrease at 12 h, but still higher than the groups at 1 h and 3 h. Within 12 hours after poisoning, the number of caspase-3 positive cell and average optical density in brain cortex of rats gradually increased. The abnormal aggregation of α-syn caused by brain edema and hypoxia may participate the early stage of neuronal apoptosis in brain cortex after acute alcoholism. Copyright© by the Editorial Department of Journal of Forensic Medicine

  4. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic- pituitary-adrenal axis activation

    PubMed Central

    Reynolds, Anna R.; Saunders, Meredith A.; Brewton, Honoree’ W.; Winchester, Sydney R.; Elgumati, Ibrahim S.; Prendergast, Mark A.

    2015-01-01

    Background The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Methods Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 1100 hrs on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60 mg/kg/i.g.) or a placebo and withdrawal was monitored. Results Peak BELs of 225.52 mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g. aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. Conclusions The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. PMID:26143299

  5. Acute oral administration of the novel, competitive and selective glucocorticoid receptor antagonist ORG 34517 reduces the severity of ethanol withdrawal and related hypothalamic-pituitary-adrenal axis activation.

    PubMed

    Reynolds, Anna R; Saunders, Meredith A; Brewton, Honoree' W; Winchester, Sydney R; Elgumati, Ibrahim S; Prendergast, Mark A

    2015-09-01

    The development of ethanol dependence is associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis and activation of type II glucocorticoid receptors (GR). These effects may contribute to withdrawal-associated anxiety, craving and relapse to drinking. The present studies examined acute and oral administration of the novel, selective and competitive GR antagonist ORG 34517 on the severity of ethanol withdrawal. Adult, male Sprague-Dawley rats were administered ethanol (4g/kg/i.g.) twice daily for 5 days followed by 2 days of withdrawal for 1, 2 or 3 consecutive cycles. Blood ethanol levels (BELs) were determined at 0930 on Day 4 of each week, while blood corticosterone levels (BCLs) were obtained at 11:00hours on the first day of each ethanol withdrawal. During early withdrawal, subjects received oral administration of ORG 345617 (60mg/kg/i.g.) or a placebo and withdrawal was monitored. Peak BELs of 225.52mg/dl were observed during the third week. Withdrawal from three cycles of the regimen produced marked behavioral abnormalities (e.g., aggression, rigidity, and hypoactivity) and significant increases in BCLs of ethanol-dependent subjects. Acute, oral administration of ORG 34517 during early withdrawal significantly reduced both the severity of ethanol withdrawal, as reflected in reduced rigidity, aggression, and hypoactivity, and elevations in BCL without producing any sedative-like effects. The present findings demonstrate that repeated ethanol exposure and withdrawal is associated with significant behavioral abnormalities and dysregulation of HPA axis activation. Further these data suggest that selective GR antagonists should be further considered as putative pharmacotherapies for treatment of ethanol dependence. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. 27 CFR 31.104 - Withdrawal of one or more partners.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Withdrawal of one or more partners. 31.104 Section 31.104 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... this part, the remaining partner, or partners, must register the change in control by filing an amended...

  7. 27 CFR 31.104 - Withdrawal of one or more partners.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of one or more partners. 31.104 Section 31.104 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... this part, the remaining partner, or partners, must register the change in control by filing an amended...

  8. Severity of Withdrawal Symptoms, Plasma Oxytocin Levels, and Treatment Outcome in Heroin Users Undergoing Acute Withdrawal.

    PubMed

    Nikolaou, Kakia; Kapoukranidou, Dorothea; Ndungu, Samuel; Floros, Georgios; Kovatsi, Leda

    2017-01-01

    Pre-clinical studies show that, following chronic opioid exposure, oxytocin neurons exhibit over-excitation upon withdrawal, causing an increase in oxytocin brain and plasma levels. Relevant clinical data on humans are scarce. This study investigates the opioid withdrawal stress effect on oxytocin plasma levels in humans. We evaluated 57 male chronic heroin users in a residential detoxification program. We determined plasma oxytocin levels by ELISA and measured the stress effects of withdrawal using the COWS scale for opioid withdrawal, the VAS scale for craving, and the Hamilton scales for anxiety and depression on the second day of admission. Out of the 57 patients enrolled in the study, 27 completed the 21-day program, while the remaining 30 dropped out prior to completion. Plasma oxytocin levels were significantly higher in those individuals who dropped out than in those who completed the program. Participants who dropped out at some stage scored higher in the COWS, VAS-Craving, and Hamilton-anxiety scales, indicating a higher stress and explaining the higher oxytocin levels. In addition, plasma oxytocin levels correlated positively with the scores achieved in the COWS and Hamilton-anxiety scales. Higher withdrawal stress levels are associated with higher plasma oxytocin levels and early treatment discharge.

  9. Increased plasma pancreatic polypeptide in chronic alcohol abuse.

    PubMed

    Fink, R S; Adrian, T E; Margot, D H; Bloom, S R

    1983-04-01

    Post-prandial plasma gastrointestinal hormone profiles were measured in nine chronic alcoholics, one and fourteen days after complete alcohol withdrawal. Basal plasma pancreatic polypeptide concentration (PP--mean +/- SE mean) was significantly greater in alcoholics (control, 28 +/- 5 pmol/l; alcoholics, post-withdrawal day 1, 62 +/- 14 pmol/l, P less than 0.05; and post-withdrawal day 14, 89 +/- 17 pmol/1, P less than 0.005). The total integrated (TIR) PP response following a test breakfast was similarly elevated (control, 442 +/- 63 units; alcoholics, day 1, 1310 +/- 231 units, P less than 0.005; day 14,1066 +/- 66, P less than 0.005). Basal and TIR values for gastrin, gastric inhibitory peptide, insulin and glucagon were similar in alcoholics and controls. As PP has been shown to inhibit pancreatic exocrine enzyme secretion, these findings may help explain the abnormal pancreatic function seen frequently in alcoholics.

  10. Differences in reporting of perceived acute effects of alcohol use, marijuana use, and simultaneous alcohol and marijuana use.

    PubMed

    Lee, Christine M; Cadigan, Jennifer M; Patrick, Megan E

    2017-11-01

    Although there are serious negative harms associated with simultaneous alcohol and marijuana (SAM) use, little is known about the self-reported acute effects of SAM use and how they may be similar to or different than effects experienced when using alcohol or marijuana only. The current study examines the perceived acute effects of SAM use, compared to using alcohol or marijuana only, as well as demographic and substance use predictors of overall SAM effects. Participants were a community sample of young adults ages 18-23 participating in a longitudinal study on social role transitions and substance use during young adulthood. Young adults who reported SAM use at least once in their lifetime were selected for the present analyses (N=315; mean age=21.42; 58% female) and reported the effects they experienced from typical alcohol use, marijuana use, and SAM use. There were significant differences in the extent to which young adults perceived the effects depending on the substances used. Most effects (i.e., clumsy, confused, dizzy, difficulty concentrating) were rated strongest when engaging in SAM use, compared to typical alcohol or marijuana use alone. Feeling high and feeling marijuana effects were rated strongest when engaging in marijuana use alone compared to SAM use, but feeling drunk was greater during SAM use compared to alcohol use alone. Greater alcohol use and increased time spent high during typical SAM use were associated with greater overall SAM effects. When young adults engage in SAM use they report experiencing greater negative physiological and cognitive effects. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Identification of a QTL in Mus musculus for alcohol preference, withdrawal, and Ap3m2 expression using integrative functional genomics and precision genetics.

    PubMed

    Bubier, Jason A; Jay, Jeremy J; Baker, Christopher L; Bergeson, Susan E; Ohno, Hiroshi; Metten, Pamela; Crabbe, John C; Chesler, Elissa J

    2014-08-01

    Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits. Copyright © 2014 by the Genetics Society of America.

  12. [Compulsory hospitalisation of patients suffering from severe drug or alcohol addiction].

    PubMed

    Höppener, P E; Godschalx-Dekker, J A; van de Wetering, B J M

    2013-01-01

    Psychiatrists treating patients with drug and alcohol addiction currently consider these afflicions to be mental disorders. If patients are so mentally disturbed that they are a danger to themselves or others, then compulsory hospitalisation seems to be an acceptable treatment option. However, it would seem that at present this solution is not normal practice in addiction care. To describe the indications for compulsory hospitalisation when mental disorders associated with addiction and withdrawal cause risks and dangers. Discussion of the indications for compulsory enforced hospitalisation supported by literature. Compulsory hospitalisation is based on the acceptance of the principle that addiction and substance abuse are mental disorders. Indications for emergency hospitalisation include intoxications, acute withdrawal symptoms and other disorders associated with substance use. Indications for longer-term measures are (self)-protection, societal isolation and the need to protect other people from danger. Factors influencing the decision-making process regarding emergency hospitalisation are motivation and treatment perspectives, mental incompetence, contraindications and conflicts between criminal law and patients’ rights. Compulsory hospitalisation deserves serious consideration as the ultimate step in treatment of intoxication, drug and alcohol dependence and withdrawal symptoms. In addition, emergency hospitalisation can be a way of averting danger, facilitating diagnosis and motivating abstinence or at least a reduction in substance use.

  13. αCaMKII Autophosphorylation Controls the Establishment of Alcohol Drinking Behavior

    PubMed Central

    Easton, Alanna C; Lucchesi, Walter; Lourdusamy, Anbarasu; Lenz, Bernd; Solati, Jalal; Golub, Yulia; Lewczuk, Piotr; Fernandes, Cathy; Desrivieres, Sylvane; Dawirs, Ralph R; Moll, Gunther H; Kornhuber, Johannes; Frank, Josef; Hoffmann, Per; Soyka, Michael; Kiefer, Falk; Schumann, Gunter; Peter Giese, K; Müller, Christian P

    2013-01-01

    The α-Ca2+/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a ‘molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKIIT286A mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKIIT286A mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKIIT286A mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKIIT286A mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA–5-HT balance as a putative mechanism. PMID:23459588

  14. Alcohol education revisited: exploring how much time we devote to alcohol education in the nursing curriculum.

    PubMed

    Cund, Audrey

    2013-01-01

    This study examines student nurses knowledge, attitudes and educational preparation to work with patients who misuse alcohol. The study begins to quantify how much time is devoted to alcohol education at one Scottish University. The study modified the Short Alcohol Attitudes Problem Perception Questionnaire (SAAPPQ) and incorporated three case vignettes to examine the student nurses knowledge, attitudes and experience of working with patients who have an alcohol problem. The questionnaire was hand delivered to a convenience sample of third year nursing students. The results show that the student nurses exhibit positive attitudes and beliefs about working with patients who have an alcohol misuse problem. A series of significant associations was found between the adult nursing cohort and their ability to include a comprehensive alcohol history in their nursing assessments (χ(2) = 19.82, df = 4, p < 0.0005); recognise signs of acute alcohol withdrawal (χ(2) = 52.26, df = 16, p < 0.000); and the psychological signs associated with alcohol misuse (χ(2) = 41.81, df = 16, p < 0.000). A baseline figure of 2.5 h of alcohol education is noted at this university. Alcohol education strongly features in three out of the five nursing programmes surveyed. Nurse education needs to focus on strategies that extend to teaching nurses how to respond, provide brief interventions and identify when to refer the patient for specialist intervention. These approaches should be universal to all areas of nursing practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Acute Alcohol Modulates Cardiac Function as PI3K/Akt Regulates Oxidative Stress

    PubMed Central

    Umoh, Nsini A.; Walker, Robin K.; Al-Rubaiee, Mustafa; Jeffress, Miara A.; Haddad, Georges E.

    2015-01-01

    Background Clinical manifestations of alcohol abuse on the cardiac muscle include defective contractility with the development of heart failure. Interestingly, low alcohol consumption has been associated with reduced risk of cardiovascular disease. Although several hypotheses have been postulated for alcoholic cardiomyopathy and for the low-dose beneficial cardiovascular effects, the precise mechanisms and mediators remain largely undefined. We hypothesize that modulation of oxidative stress by PI3K/Akt plays a key role in the cardiac functional outcome to acute alcohol exposure. Methods Thus, acutely exposed rat cardiac tissue and cardiocytes to low (LA: 5 mM), moderate (MA: 25 mM), and high (HA: 100 mM) alcohol were assessed for markers of oxidative stress in the presence and absence of PI3K/Akt activators (IGF-1 0.1 μM or constitutively active PI3K: Ad.BD110 transfection) or inhibitor (LY294002 1 μMor Akt-negative construct Ad.Akt(K179M) transfection). Results Acute LA reduced Akt, superoxide dismutase (SOD-3) and NFκB, ERK1, and p38 MAPK gene expression. Acute HA only increased that of SOD-3 and NFκB. These effects were generally inhibited by Ad.Akt(K179M) and enhanced with Ad.BD110 transfection. In parallel, LA reduced but HA enhanced Akt activity, which was reversed by IGF-1 and inhibited by Ad.Akt(K179M), respectively. Also, LA reduced caspase 3/7 activity and oxidative stress, while HA increased both. The former was blocked, while the latter effect was enhanced by Ad.Akt(K179M). The reverse was true with PI3K/Akt activation. This translated into reduced viability with HA, with no effect with LA. On the functional level, acute LA improved cardiac output and ejection fraction, mainly through increased stroke volume. This was accompanied with enhanced end-systolic pressure–volume relationship and preload recruitable stroke work. Opposite effect was recorded for HA. LA and HA in vivo functional effects were alleviated by LY and enhanced by IGF-1 treatment

  16. Dutch courage? Effects of acute alcohol consumption on self-ratings and observer ratings of foreign language skills.

    PubMed

    Renner, Fritz; Kersbergen, Inge; Field, Matt; Werthmann, Jessica

    2018-01-01

    A popular belief is that alcohol improves the ability to speak in a foreign language. The effect of acute alcohol consumption on perceived foreign language performance and actual foreign language performance in foreign language learners has not been investigated. The aim of the current study was to test the effects of acute alcohol consumption on self-rated and observer-rated verbal foreign language performance in participants who have recently learned this language. Fifty native German speakers who had recently learned Dutch were randomized to receive either a low dose of alcohol or a control beverage that contained no alcohol. Following the experimental manipulation, participants took part in a standardized discussion in Dutch with a blinded experimenter. The discussion was audio-recorded and foreign language skills were subsequently rated by two native Dutch speakers who were blind to the experimental condition (observer-rating). Participants also rated their own individual Dutch language skills during the discussion (self-rating). Participants who consumed alcohol had significantly better observer-ratings for their Dutch language, specifically better pronunciation, compared with those who did not consume alcohol. However, alcohol had no effect on self-ratings of Dutch language skills. Acute alcohol consumption may have beneficial effects on the pronunciation of a foreign language in people who have recently learned that language.

  17. Alcohol and violence: neuropeptidergic modulation of monoamine systems

    PubMed Central

    Miczek, Klaus A.; DeBold, Joseph F.; Hwa, Lara S.; Newman, Emily L.; de Almeida, Rosa M. M.

    2015-01-01

    Neurobiological processes underlying the epidemiologically-established link between alcohol and several types of social, aggressive, and violent behavior remain poorly understood. Acute low doses of alcohol, as well as withdrawal from long-term alcohol use, may lead to escalated aggressive behavior in a subset of individuals. An urgent task will be to disentangle the host of interacting genetic and environmental risk factors in individuals that are predisposed to engage in escalated aggressive behavior. The modulation of 5-hydroxytryptamine impulse flow by gamma-aminobutyric acid (GABA) and glutamate, acting via distinct ionotropic and metabotropic receptor subtypes in the dorsal raphe nucleus during alcohol consumption, is of critical significance in the suppression and escalation of aggressive behavior. In anticipation and reaction to aggressive behavior, neuropeptides such as corticotropin-releasing factor, neuropeptide Y, opioid peptides, and vasopressin interact with monoamines, GABA, and glutamate to attenuate and amplify aggressive behavior in alcohol-consuming individuals. These neuromodulators represent novel molecular targets for intervention that await clinical validation. Intermittent episodes of brief social defeat during aggressive confrontations are sufficient to cause long-lasting neuroadaptations that can lead to the escalation of alcohol consumption. PMID:26285061

  18. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhir

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day formore » 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.« less

  19. Relationship of nicotine deprivation and indices of alcohol use behavior to implicit alcohol and cigarette approach cognitions in smokers.

    PubMed

    Cohn, Amy; Ehlke, Sarah; Cobb, Caroline O

    2017-04-01

    Alcohol and smoking frequently co-occur and alcohol is a primary trigger for smoking behavior and relapse back to smoking. This study examined whether several indices of alcohol use behavior and consequences of use would be associated with changes in implicit alcohol-approach versus implicit cigarette-approach cognitions under cigarette deprived and non-deprived cognitions in 109 smokers who drank at risky or non-risky levels. An Implicit Association Task (IAT) measured how quickly respondents paired alcohol and cigarette pictures with approach and avoid words. Regression analyses examined the associations of quantity/frequency, proportion heavy drinking days, number of DSM-IV alcohol use disorder (AUD) symptoms, and risky drinking status to IAT scores under deprived conditions, controlling for IAT order effects, non-deprived IAT score, and deprived cigarette craving and withdrawal. Interactions with craving and withdrawal intensity were also examined. Results showed a significant positive association between proportion of heavy drinking days and stronger alcohol-approach than cigarette-approach motivations when deprived. There was also a conditional association of AUD symptoms to alcohol-approach motivations among respondents reporting more intense withdrawal when deprived. Alcohol quantity and frequency, as well as risky drinking status were unrelated to change in IAT scores. Findings suggest that cigarette deprivation may magnify motivation to drink, rather than smoke, among smokers who engage in more frequent bouts of heavy drinking and who report more alcohol-related problems. Results also show relative momentary and unconscious "preference" or choice for alcohol over cigarettes in some high-risk smokers, when cigarette craving and withdrawal are high. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Alcohol and Caffeine: The Perfect Storm

    PubMed Central

    O'Brien, Mary Claire

    2011-01-01

    Although it is widely believed that caffeine antagonizes the intoxicating effects of alcohol, the molecular mechanisms underlying their interaction are incompletely understood. It is known that both caffeine and alcohol alter adenosine neurotransmission, but the relationship is complex, and may be dose dependent. In this article, we review the available literature on combining caffeine and alcohol. Ethical constraints prohibit laboratory studies that would mimic the high levels of alcohol intoxication achieved by many young people in real-world settings, with or without the addition of caffeine. We propose a possible neurochemical mechanism for the increase in alcohol consumption and alcohol-related consequences that have been observed in persons who simultaneously consume caffeine. Caffeine is a nonselective adenosine receptor antagonist. During acute alcohol intake, caffeine antagonizes the “unwanted” effects of alcohol by blocking the adenosine A1 receptors that mediate alcohol's somnogenic and ataxic effects. The A1 receptor–mediated “unwanted” anxiogenic effects of caffeine may be ameliorated by alcohol-induced increase in the extracellular concentration of adenosine. Moreover, by means of interactions between adenosine A2A and dopamine D2 receptors, caffeine-mediated blockade of adenosine A2A receptors can potentiate the effects of alcohol-induced dopamine release. Chronic alcohol intake decreases adenosine tone. Caffeine may provide a “treatment” for the withdrawal effects of alcohol by blocking the effects of upregulated A1 receptors. Finally, blockade of A2A receptors by caffeine may contribute to the reinforcing effects of alcohol. PMID:24761263

  1. Alcohol-impaired speed and accuracy of cognitive functions: a review of acute tolerance and recovery of cognitive performance.

    PubMed

    Schweizer, Tom A; Vogel-Sprott, Muriel

    2008-06-01

    Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews the results of recent research using these tasks to test the development of acute tolerance in cognitive performance and recovery from impairment during declining BACs. Results show that speed and accuracy do not necessarily agree in detecting cognitive impairment, and this mismatch most frequently occurs during declining BACs. Speed of cognitive performance usually recovers from impairment to drug-free levels during declining BACs, whereas alcohol-increased errors fail to diminish. As a consequence, speed of cognitive processing tends to develop acute tolerance, but no such tendency is shown in accuracy. This "acute protracted error" phenomenon has not previously been documented. The findings pose a challenge to the theory of alcohol tolerance on the basis of physiological adaptation and raise new research questions concerning the independence of speed and accuracy of cognitive processes, as well as hemispheric lateralization of alcohol effects. The occurrence of alcohol-induced protracted cognitive errors long after speed returned to normal is identified as a potential threat to the safety of social drinkers that requires urgent investigation.

  2. Sequence variations of the human MPDZ gene and association with alcoholism in subjects with European ancestry.

    PubMed

    Karpyak, Victor M; Kim, Jeong-Hyun; Biernacka, Joanna M; Wieben, Eric D; Mrazek, David A; Black, John L; Choi, Doo-Sup

    2009-04-01

    Mpdz gene variations are known contributors of acute alcohol withdrawal severity and seizures in mice. To investigate the relevance of these findings for human alcoholism, we resequenced 46 exons, exon-intron boundaries, and 2 kilobases in the 5' region of the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures (AWS), 59 subjects with a history of alcohol withdrawal without AWS, and 64 Coriell samples from self-reported nonalcoholic subjects [all European American (EA) ancestry] and compared with the Mpdz sequences of 3 mouse strains with different propensity to AWS. To explore potential associations of the human MPDZ gene with alcoholism and AWS, single SNP and haplotype analyses were performed using 13 common variants. Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequence comparison revealed that the human gene does not have variations identical to those comprising Mpdz gene haplotype associated with AWS in mice. We also found no significant association between MPDZ haplotypes and AWS in humans. However, a global test of haplotype association revealed a significant difference in haplotype frequencies between alcohol-dependent subjects without AWS and Coriell controls (p = 0.015), suggesting a potential role of MPDZ in alcoholism and/or related phenotypes other than AWS. Haplotype-specific tests for the most common haplotypes (frequency > 0.05), revealed a specific high-risk haplotype (p = 0.006, maximum statistic p = 0.051), containing rs13297480G allele also found to be significantly more prevalent in alcoholics without AWS compared with nonalcoholic Coriell subjects (p = 0.019). Sequencing of MPDZ gene in individuals with EA ancestry revealed no variations in the sites identical to those associated with AWS in mice. Exploratory haplotype and single SNP association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not AWS. Further functional genomic analysis of MPDZ

  3. Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury

    PubMed Central

    Wang, Yuhua; Liu, Yanlong; Sidhu, Anju; Ma, Zhenhua; McClain, Craig

    2012-01-01

    Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (109 colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2α, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel

  4. Molecular mechanisms of synaptic remodeling in alcoholism

    PubMed Central

    Kyzar, Evan J.; Pandey, Subhash C.

    2015-01-01

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the “dark side” of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. PMID:25623036

  5. Molecular mechanisms of synaptic remodeling in alcoholism.

    PubMed

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

  6. Paracetamol, alcohol and the liver

    PubMed Central

    Prescott, Laurie F

    2000-01-01

    It is claimed that chronic alcoholics are at increased risk of paracetamol (acetaminophen) hepatotoxicity not only following overdosage but also with its therapeutic use. Increased susceptibility is supposed to be due to induction of liver microsomal enzymes by ethanol with increased formation of the toxic metabolite of paracetamol. However, the clinical evidence in support of these claims is anecdotal and the same liver damage after overdosage occurs in patients who are not chronic alcoholics. Many alcoholic patients reported to have liver damage after taking paracetamol with ‘therapeutic intent’ had clearly taken substantial overdoses. No proper clinical studies have been carried out to investigate the alleged paracetamol–alcohol interaction and acute liver damage has never been produced by therapeutic doses of paracetamol given as a challenge to a chronic alcoholic. The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects. In animals, chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol). However, in man, chronic alcohol ingestion causes only modest (about twofold) and short-lived induction of CYP2E1, and there is no corresponding increase (as claimed) in the toxic metabolic activation of paracetamol. The paracetamol–ethanol interaction is not specific for any one isoform of cytochrome P450, and it seems that isoenzymes other than CYP2E1 are primarily responsible for the oxidative metabolism of paracetamol in man. Acute ethanol inhibits the microsomal oxidation of paracetamol both in animals and man. This protects against liver damage in animals and there is evidence that it also does so in man. The protective effect disappears when ethanol is eliminated and the relative timing of ethanol and paracetamol intake is critical. In many of the reports

  7. Alcohol consumption decreases lactate clearance in acutely injured patients☆

    PubMed Central

    Dezman, Zachary D.W.; Comer, Angela C.; Narayan, Mayur; Scalea, Thomas M.; Hirshon, Jon Mark; Smith, Gordon S.

    2017-01-01

    Introduction Alcohol, a common risk factor for injury, has direct toxic effects on the liver. The use of lactate clearance has been well described as an indicator of the adequacy of resuscitation in injured patients. We investigated whether acutely injured patients with positive blood alcohol content (+BAC) had less lactate clearance than sober patients. Methods We conducted a retrospective cohort study of acutely injured patients treated at an urban Level 1 trauma centre between January 2010 and December 2012. Blood alcohol and venous lactate levels were measured on all patients at the time of arrival. Study subjects were patients transported directly from the scene of injury, who had an elevated lactate concentration on arrival (≥3.0 mmol/L) and at least one subsequent lactate measurement within 24 h after admission. Lactate clearance ([Lactate1 − Lactate2]/Lactate1) was calculated for all patients. Chi-squared tests were used to compare values from sober and intoxicated subjects. Lactate clearance was plotted against alcohol levels and stratified by age and Injury Severity Score (ISS). Results Serial lactate concentration measurements were obtained in 3910 patients; 1674 of them had +BAC. Patients with +BAC were younger (mean age: 36.6 [SD 14.7] vs 41.0 [SD 19.9] years [p = 0.0001]), were more often male (83.4% vs 75.9% [p = 0.0001]), had more minor injuries (ISS < 9) (33.8% vs 27.1% [p = 0.0001]), had a lower in-hospital mortality rate (1.4% vs 3.9% [p = 0.0001]), but also had lower average lactate clearance (37.8% vs 47.6% [p = 0.0001]). The lactate clearance of the sober patients (47.6 [SD 33.5]) was twice that of those with +BAC >400 (23.5 [SD 6.5]). Lactate clearance decreased with increasing BAC irrespective of age and ISS. Conclusions In a large group of acutely injured patients, a dose-dependent decrease in lactate clearance was seen in those with elevated BAC. This relationship will cause a falsely elevated lactate reading or prolong lactate

  8. Family Based Prevention of Alcohol and Risky Sex for Older Teens

    ClinicalTrials.gov

    2018-05-08

    Alcohol Drinking; Alcohol Intoxication; Alcohol Poison; Alcohol-Related Disorders; Alcohol Impairment; Alcohol Withdrawal; Alcohol Abstinence; Alcohol; Harmful Use; Sex Behavior; Sexual Aggression; Sexual Harassment; Relation, Interpersonal

  9. Use of alcohol hand sanitizer as an infection control strategy in an acute care facility.

    PubMed

    Hilburn, Jessica; Hammond, Brian S; Fendler, Eleanor J; Groziak, Patricia A

    2003-04-01

    Nosocomial infections are a major problem in health care facilities, resulting in extended durations of care, substantial morbidity and mortality, and excess costs. Since alcohol gel hand sanitizers combine high immediate antimicrobial efficacy with ease of use, this study was carried out to determine the effect of the use of an alcohol gel hand sanitizer by caregivers on infection types and rates in an acute care facility. Patients were educated about the study through a poster on the unit, and teachable patients were given portable bottles of the alcohol hand gel for bedside use, along with an educational brochure explaining how and why to practice good hand hygiene. Infection rate and type data were collected in 1 unit of a 498-bed acute care facility for 16 months (February 2000 to May 2001). An alcohol gel hand sanitizer was provided and used by caregivers in the orthopedic surgical unit of the facility during this period. The primary infection types (more than 80%) found were urinary tract (UTI) and surgical site (SSI) infections. Infection types and rates for the unit during the period the alcohol hand sanitizer (intervention) was used were compared with the infection types and rates for the same unit when the alcohol hand sanitizer was not used (baseline); the results demonstrated a 36.1% decrease in infection rates for the 10-month period that the hand sanitizer was used. This study indicates that use of an alcohol gel hand sanitizer can decrease infection rates and provide an additional tool for an effective infection control program in acute care facilities.

  10. Differential effects of acute amphetamine and phencyclidine treatment and withdrawal from repeated amphetamine or phencyclidine treatment on social interaction and social memory in rats.

    PubMed

    Li, Ming; He, Wei; Munro, Rebecca

    2012-06-01

    Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals with the same partner rat (termed "AAAA" day). One day later, the rats were tested with the previous partner in the first three sessions and with a new partner rat in the final session (termed "AAAB" day). The results show that acute AMPH treatment (1.5 mg/kg, sc) significantly reduced the time spent on social interaction, but did not affect social recognition on the first day. Acute AMPH only disrupted social recognition on the second day of drug testing. In contrast, acute PCP treatment (2.0 mg/kg, sc) had no effect on time spent on social interaction, but did significantly disrupt social recognition on both days. Withdrawal from repeated AMPH (3.0 mg/kg/day for 7 days, ip) or PCP (5.0 mg/kg/twice daily for 7 days, ip) treatment did not affect social interaction or social recognition, indicating a lack of long-term detrimental effect of repeated AMPH or PCP treatment. These results suggest that acute AMPH treatment at a low dose (1.5 mg/kg) may be useful in modeling social withdrawal symptoms of schizophrenia, whereas acute PCP treatment at a similar dose range (2.0 mg/kg) may be useful in modeling the social cognitive deficit of schizophrenia. © 2012 The Institute of Psychology, Chinese Academy of Sciences and Blackwell Publishing Asia Pty Ltd.

  11. A Case Report of Nystagmus with Acute Comitant Esotropia Secondary to Heroin Withdrawal: A Novel Presentation

    PubMed Central

    Rabin, Richard L.

    2015-01-01

    Background Acute comitant esotropia secondary to heroin withdrawal is a rarely reported phenomenon that has never been described with nystagmus. Adverse effects of heroin on eye alignment were first reported in soldiers returning from Vietnam, yet no theory is generally accepted as the cause of these abnormalities. Method We present a case of a 22-year-old female who developed 40 prism diopters of alternating comitant esotropia with nystagmus 8 days after abrupt heroin cessation, review the existing literature, and propose a novel hypothesis for this phenomenon. Results After 76 days, her esotropia resolved, and she was left with 7 prism diopters of esophoria. Conclusion This case demonstrates that acquired nystagmus can present in addition to acute-onset esotropia after abrupt heroin cessation. We compare and contrast the theories of this mechanism and review the literature. PMID:26483678

  12. Acute effects of alcohol on the development of intrusive memories.

    PubMed

    Bisby, James A; Brewin, Chris R; Leitz, Julie R; Valerie Curran, H

    2009-07-01

    Post-traumatic stress disorder is characterised by repeated intrusive imagery of the traumatic event. Despite alcohol's impairing effect on memory and frequent involvement in real-life trauma, virtually nothing is known of the interaction between alcohol and trauma memory. We aimed to investigate the acute alcohol effects on spontaneous memories following a trauma film as well as explicit memory for the film. Utilising an independent-group double-blind design, 48 healthy volunteers were randomly allocated to receive alcohol of 0.4 or 0.8 g/kg or a matched placebo drink. A stressful film was viewed post-drink. Skin conductance was monitored throughout and mood and dissociative symptoms were indexed. Volunteers recorded their spontaneous memories of the film daily in an online diary over the following week. Their explicit memory for both gist and details of the film was tested on day 7. Intriguingly, an inverted 'U' alcohol dose-response was observed on intrusive memories with a low dose of alcohol increasing memory intrusions while a high dose decreased intrusions. In contrast, explicit memory performance after 7 days showed a linear dose-response effect of alcohol with both recall and recognition decreasing as dose increased. These findings highlight a striking differential pattern of alcohol's effects on spontaneous memories as compared with explicit memories. Alcohol's effect on spontaneous memories may reflect a dose-dependent impairment of two separate memory systems integral to the processing of different aspects of a traumatic event.

  13. The Acute Administration of the Selective Dopamine D3 Receptor Antagonist SB-277011A Reverses Conditioned Place Aversion Produced by Naloxone Precipitated Withdrawal From Acute Morphine Administration in Rats

    PubMed Central

    RICE, ONARAE V.; GARDNER, ELIOT L.; HEIDBREDER, CHRISTIAN A.; ASHBY, CHARLES R.

    2014-01-01

    We examined the effect of SB-277011A, a selective D3 receptor antagonist, on the conditioned place aversion (CPA) response associated with naloxone-induced withdrawal from acute morphine administration in male Sprague-Dawley rats. Morphine (5.6 mg/kg i.p.) was given, followed 4 hrs later by naloxone (0.3 mg/kg i.p.) and prior to placing the animals in one specific chamber of the test apparatus. All animals were subjected to 2 of these trials. A significant CPA occurred in animals that received an i.p. injection of vehicle 30 minutes prior to the measurement of chamber preference. The pretreatment of animals (30 minutes prior to testing) with 3 mg/kg i.p. of SB-277011A did not significantly alter the CPA compared to animals treated with vehicle (1 ml/kg i.p. of deionized distilled water). In contrast, the acute pretreatment of animals with 6, 12 or 24 mg/kg i.p. of SB-277011A significantly decreased the CPA compared to vehicle-treated animals. In fact, the 12 and 24 mg/kg doses of SB-277011A significantly increased the time spent in the chamber where animals were paired with morphine and naloxone. These results suggest that the selective antagonism of D3 receptors attenuates the CPA produced by a model of naloxone-induced withdrawal from acute morphine dependence. PMID:21905128

  14. Effects of Acute Alcohol Intoxication on Empathic Neural Responses for Pain

    PubMed Central

    Hu, Yang; Cui, Zhuoya; Fan, Mingxia; Pei, Yilai; Wang, Zhaoxin

    2018-01-01

    The questions whether and how empathy for pain can be modulated by acute alcohol intoxication in the non-dependent population remain unanswered. To address these questions, a double-blind, placebo-controlled, within-subject study design was adopted in this study, in which healthy social drinkers were asked to complete a pain-judgment task using pictures depicting others' body parts in painful or non-painful situations during fMRI scanning, either under the influence of alcohol intoxication or placebo conditions. Empathic neural activity for pain was reduced by alcohol intoxication only in the dorsal anterior cingulate cortex (dACC). More interestingly, we observed that empathic neural activity for pain in the right anterior insula (rAI) was significantly correlated with trait empathy only after alcohol intoxication, along with impaired functional connectivity between the rAI and the fronto-parietal attention network. Our results reveal that alcohol intoxication not only inhibits empathic neural responses for pain but also leads to trait empathy inflation, possibly via impaired top-down attentional control. These findings help to explain the neural mechanism underlying alcohol-related social problems. PMID:29354044

  15. Effects of Acute Alcohol Intoxication on Empathic Neural Responses for Pain.

    PubMed

    Hu, Yang; Cui, Zhuoya; Fan, Mingxia; Pei, Yilai; Wang, Zhaoxin

    2017-01-01

    The questions whether and how empathy for pain can be modulated by acute alcohol intoxication in the non-dependent population remain unanswered. To address these questions, a double-blind, placebo-controlled, within-subject study design was adopted in this study, in which healthy social drinkers were asked to complete a pain-judgment task using pictures depicting others' body parts in painful or non-painful situations during fMRI scanning, either under the influence of alcohol intoxication or placebo conditions. Empathic neural activity for pain was reduced by alcohol intoxication only in the dorsal anterior cingulate cortex (dACC). More interestingly, we observed that empathic neural activity for pain in the right anterior insula (rAI) was significantly correlated with trait empathy only after alcohol intoxication, along with impaired functional connectivity between the rAI and the fronto-parietal attention network. Our results reveal that alcohol intoxication not only inhibits empathic neural responses for pain but also leads to trait empathy inflation, possibly via impaired top-down attentional control. These findings help to explain the neural mechanism underlying alcohol-related social problems.

  16. Protective Action of Se-Supplement Against Acute Alcoholism Is Regulated by Selenoprotein P (SelP) in the Liver.

    PubMed

    Zhang, Zhenbiao; Guo, Yingfang; Qiu, Changwei; Deng, Ganzhen; Guo, Mengyao

    2017-02-01

    Acute alcoholism is a major cause of cirrhosis and liver failure around the world. Selenium (Se) is an essential micronutrient promoting liver health in humans and animals. Selenoprotein P (SelP) is a glycoprotein secreted within the liver, which interacts with cytokines and the growth factor pathway to provide protection for hepatic cells. The present study was conducted to confirm the effect and mechanism of Se and SelP action in livers affected by acute alcoholism. In this study, a mouse model of acute alcoholism, as well as a hepatocyte model, was successfully established. The Se content of the liver was detected by atomic fluorescence spectrophotometry. The expression of messenger RNA (mRNA) was analyzed by quantitative polymerase chain reaction (qPCR). The protein expression of inflammatory factors was detected by ELISA. The other proteins were analyzed by western blotting. The results showed that pathological damage to the liver was gradually weakened by Se-supplementation, which was evaluated by hematoxylin and eosin (H&E) and TUNEL staining. Se-supplementation inhibited expression of pro-inflammatory factors TNF-α and IL-1β and promoted production of anti-inflammatory cytokine IL-10 in the liver with acute alcoholism. Se-supplementation also prevented the apoptosis of hepatocytes by suppressing the cleavage of caspases-9, 3, 6, 7, and poly(ADP-ribose) polymerase (PARP). Through correlational analysis, it was determined that the effects of Se-supplement were closely related to SelP expression, inflammatory cytokines, and apoptosis molecule production. The sienna of SelP further confirmed the protective action of Se-supplementation on the liver and that the mechanism of SelP involves the regulation of inflammatory cytokines and apoptosis molecules in acute alcoholism. These findings provide information regarding a new potential target for the treatment of acute alcoholism.

  17. Caffeine withdrawal and high-intensity endurance cycling performance.

    PubMed

    Irwin, Christopher; Desbrow, Ben; Ellis, Aleisha; O'Keeffe, Brooke; Grant, Gary; Leveritt, Michael

    2011-03-01

    In this study, we investigated the impact of a controlled 4-day caffeine withdrawal period on the effect of an acute caffeine dose on endurance exercise performance. Twelve well-trained and familiarized male cyclists, who were caffeine consumers (from coffee and a range of other sources), were recruited for the study. A double-blind placebo-controlled cross-over design was employed, involving four experimental trials. Participants abstained from dietary caffeine sources for 4 days before the trials and ingested capsules (one in the morning and one in the afternoon) containing either placebo or caffeine (1.5 mg · kg(-1) body weight · day(-1)). On day 5, capsules containing placebo or caffeine (3 mg · kg(-1) body weight) were ingested 90 min before completing a time trial, equivalent to one hour of cycling at 75% peak sustainable power output. Hence the study was designed to incorporate placebo-placebo, placebo-caffeine, caffeine-placebo, and caffeine-caffeine conditions. Performance time was significantly improved after acute caffeine ingestion by 1:49 ± 1:41 min (3.0%, P = 0.021) following a withdrawal period (placebo-placebo vs. placebo-caffeine), and by 2:07 ± 1:28 min (3.6%, P = 0.002) following the non-withdrawal period (caffeine-placebo vs. caffeine-caffeine). No significant difference was detected between the two acute caffeine trials (placebo-caffeine vs. caffeine-caffeine). Average heart rate throughout exercise was significantly higher following acute caffeine administration compared with placebo. No differences were observed in ratings of perceived exertion between trials. A 3 mg · kg(-1) dose of caffeine significantly improves exercise performance irrespective of whether a 4-day withdrawal period is imposed on habitual caffeine users.

  18. Acute rejection characteristics from a prospective, randomized, double-blind, placebo-controlled multicenter trial of early corticosteroid withdrawal.

    PubMed

    Gaber, A Osama; Moore, Linda W; Alloway, Rita R; Woodle, E Steve; Pirsch, John; Shihab, Fuad; Henning, Alice; Fitzsimmons, William; Holman, John; Reisfield, Robin; First, M Roy

    2013-02-27

    This report characterizes acute rejection and rejection outcomes in subjects randomized to continuous corticosteroid therapy (CCS) or early corticosteroid withdrawal (CSWD; 7 days after transplantation) in the Astellas Blinded CSWD Trial. The Astellas Blinded CSWD Trial was a 5-year, prospective, multicenter, randomized, double-blind trial of early CCS withdrawal in 386 kidney transplant recipients (195 CCS and 191 CSWD). Tacrolimus and mycophenolate mofetil were required as well as either rabbit antithymocyte globulin or interleukin-2 receptor antibody induction. Biopsy-confirmed acute rejection (BCAR) was grade 1A or higher by Banff criteria. This report also provides borderline changes (BL) that did not meet Banff grade 1A included with BCAR (BCAR+BL). BCAR+BL was 25 (12.8%) in CCS group and 42 (22.0%) in CSWD group (P=0.022). Early BCAR+BL (first 90 days after transplantation) was less frequent in CCS (n=5 [2.6%]) than in CSWD (n=22 [11.5%]; P<0.001). Among non-African-American subjects, early BCAR+BL occurred more often in CSWD (n=20 [12.7%]) versus CCS (n=2 [1.3%]; P<0.001). Late acute rejection (>2 years) occurred more often in African-American subjects in CCS (n=5 [13.9%]) than in CSWD (n=0; P=0.056). Risk factors were CSWD (hazard ratio [HR], 4.72; P<0.002) and human leukocyte antigen mismatch (HR, 1.48; P<0.005) for early BCAR+BL and CSWD (HR, 1.9; P<0.02), human leukocyte antigen mismatch (HR, 1.2; P<0.01), and age (HR, 0.97; P<0.002) for 5-year rejection. The HR for graft loss associated with BCAR+BL was 8.8. BCAR+BL may occur more frequently during the early period after transplantation under an early CSWD regimen with tacrolimus plus induction compared with CCS, particularly among non-African-Americans.

  19. Severity of acute illness is associated with baseline readiness to change in medical intensive care unit patients with unhealthy alcohol use.

    PubMed

    Clark, Brendan J; Smart, Alexandra; House, Robert; Douglas, Ivor; Burnham, Ellen L; Moss, Marc

    2012-03-01

    Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one-third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use. We performed a cross-sectional observational study of current regular drinkers in 3 medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low-risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient's acute illness was assessed by calculating the Acute Physiologic and Chronic Health Evaluation II (APACHE II) score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires. Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHE II score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale; p < 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term). Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy alcohol use as potential effect modifiers

  20. Nitrendipine decreases benzodiazepine withdrawal seizures but not the development of benzodiazepine tolerance or withdrawal signs.

    PubMed Central

    Dolin, S. J.; Patch, T. L.; Rabbani, M.; Siarey, R. J.; Bowhay, A. R.; Little, H. J.

    1990-01-01

    1. The effects of the calcium channel blocking agent, nitrendipine, were studied on seizures in mice produced during withdrawal from chronic benzodiazepine treatment and on the development of tolerance to benzodiazepines. 2. Nitrendipine produced a dose-dependent decrease in seizure incidence, when seizures were produced by the partial inverse agonist FG7142 during withdrawal from seven days treatment with flurazepam. 3. Nitrendipine did not raise the seizure thresholds in naïve mice to the full inverse agonist methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), or to the gamma-aminobutyric acid (GABA) antagonist, bicuculline. 4. When given concurrently with flurazepam for seven days, nitrendipine did not affect the incidence of seizures during flurazepam withdrawal. 5. When given concurrently with the benzodiazepines, nitrendipine did not prevent the development of tolerance to midazolam general anaesthesia or tolerance to the ataxic actions of flurazepam or midazolam. 6. Chronic treatment with flurazepam for seven days did not affect the Kd or Bmax of [3H]-nimodipine binding in mouse whole brain or cerebral cortex. 7. These results with benzodiazepines are partially in contrast with those for ethanol, where nitrendipine not only decreased ethanol withdrawal seizures when given acutely, but also prevented the development of tolerance and withdrawal signs when given concurrently with ethanol. However, they do confirm the selectivity of nitrendipine for withdrawal-induced seizures. PMID:1963805

  1. Differences in Acute Alcohol-Induced Behavioral Responses Among Zebrafish Populations

    PubMed Central

    Gerlai, Robert; Ahmad, Fahad; Prajapati, Sonal

    2009-01-01

    Background With the arsenal of genetic tools available for zebrafish, this species has been successfully used to investigate the genetic aspects of human diseases from developmental disorders to cancer. Interest in the behavior and brain function of zebrafish is also increasing as CNS disorders may be modeled and studied with this species. Alcoholism and alcohol abuse are among the most devastating and costliest diseases. However, the mechanisms of these diseases are not fully understood. Zebrafish has been proposed as a model organism to study such mechanisms. Characterization of alcohol’s effects on zebrafish is a necessary step in this research. Methods Here, we compare the effects of acute alcohol (EtOH) administration on the behavior of zebrafish from 4 distinct laboratory-bred populations using automated as well as observation based behavioral quantification methods. Results Alcohol treatment resulted in significant dose-dependent behavioral changes but the dose–response trajectories differed among zebrafish populations. Conclusions The results demonstrate for the first time a genetic component in alcohol responses in adult zebrafish and also show the feasibility of high throughput behavioral screening. We discuss the exploration and exploitation of the genetic differences found. PMID:18652595

  2. The 1H-NMR-based metabolite profile of acute alcohol consumption: A metabolomics intervention study

    PubMed Central

    Mason, Shayne; Mienie, Lodewyk J.; Wevers, Ron A.; Westerhuis, Johan A.

    2018-01-01

    Metabolomics studies of disease conditions related to chronic alcohol consumption provide compelling evidence of several perturbed metabolic pathways underlying the pathophysiology of alcoholism. The objective of the present study was to utilize proton nuclear magnetic resonance (1H-NMR) spectroscopy metabolomics to study the holistic metabolic consequences of acute alcohol consumption in humans. The experimental design was a cross-over intervention study which included a number of substances to be consumed—alcohol, a nicotinamide adenine dinucleotide (NAD) supplement, and a benzoic acid-containing flavoured water vehicle. The experimental subjects—24 healthy, moderate-drinking young men—each provided six hourly-collected urine samples for analysis. Complete data sets were obtained from 20 of the subjects and used for data generation, analysis and interpretation. The results from the NMR approach produced complex spectral data, which could be resolved sufficiently through the application of a combination of univariate and multivariate methods of statistical analysis. The metabolite profiles resulting from acute alcohol consumption indicated that alcohol-induced NAD+ depletion, and the production of an excessive amount of reducing equivalents, greatly perturbed the hepatocyte redox homeostasis, resulting in essentially three major metabolic disturbances—up-regulated lactic acid metabolism, down-regulated purine catabolism and osmoregulation. Of these, the urinary excretion of the osmolyte sorbitol proved to be novel, and suggests hepatocyte swelling due to ethanol influx following acute alcohol consumption. Time-dependent metabolomics investigations, using designed interventions, provide a way of interpreting the variation induced by the different factors of a designed experiment, thereby also giving methodological significance to this study. The outcomes of this approach have the potential to significantly advance our understanding of the serious impact of

  3. Experimental acute alcohol pancreatitis-related liver damage and endotoxemia: synbiotics but not metronidazole have a protective effect.

    PubMed

    Marotta, F; Barreto, R; Wu, C C; Naito, Y; Gelosa, F; Lorenzetti, A; Yoshioka, M; Fesce, E

    2005-01-01

    The aim of this study was to test the effect of gut manipulation by either novel synbiotics or by metronidazole on either endotoxemia or the severity of liver damage in the course of acute pancreatitis from alcohol ingestion. Sprague-Dawley rats were fed for 1 week through an intragastric tube a liquid diet with either: (i) 1 mL t.i.d. of a mixture of synbiotics (Lactobacillus acidophilus, Lactobacillus helveticus and Bifidobacterium in an enriched medium); (ii) 20 mg/kg t.i.d. metronidazole; or (iii) standard diet. Then, acute pancreatitis was induced by caerulein and when the disease was full-blown, rats were fed an alcohol-rich diet. Synbiotic and metronidazole treatment was given for a further 2 weeks. Transaminase and endotoxemia levels were measured before treatment, after 6 h, after 24 h and 2 weeks later, at the time the rats were killed. Liver samples were obtained for histological analysis. Synbiotics but not metronidazole improved the acute pancreatitis-induced increase in endotoxemia and transaminase levels. The addition of alcohol worsened these variables to a limited extent in the synbiotic-treated group, while metronidazole had a negative effect on liver damage. Gut flora pretreatment with synbiotics was able to effectively protect against endotoxin/bacterial translocation, as well as liver damage in the course of acute pancreatitis and concomitant heavy alcohol consumption. The beneficial effect of synbiotics on liver histology seems to be correlated with endotoxemia. Metronidazole did not produce such a beneficial effect; in fact, it further worsened liver damage when alcohol was added to the background of ongoing acute pancreatic inflammation.

  4. Acute Alcohol Effects on Attentional Bias in Heavy and Moderate Drinkers

    PubMed Central

    Weafer, Jessica; Fillmore, Mark T.

    2012-01-01

    Heavy drinkers show an increased attentional bias to alcohol-related stimuli compared to moderate drinkers, and this bias is thought to promote motivation for alcohol consumption (Field & Cox, 2008). Studies have begun to examine acute alcohol effects on attentional bias, however little is known regarding how these effects might differ based on drinker type. Further, the degree to which attentional bias in response to alcohol is associated with excessive alcohol consumption remains unexplored. For the current study, 20 heavy drinkers and 20 moderate drinkers completed a visual probe task in response to placebo and two active doses of alcohol (0.45 g/kg and 0.65 g/kg). Participants’ eye-movements were monitored and attentional bias was calculated as the difference in time spent focused on alcohol compared to neutral images. Participants’ alcohol consumption was assessed by a timeline follow-back calendar and a laboratory ad lib consumption task. Results showed that heavy drinkers displayed significantly greater attentional bias than did moderate drinkers following placebo. However, heavy drinkers displayed a dose-dependent decrease in attentional bias following alcohol, whereas the drug had no effect in moderate drinkers. Individual differences in attentional bias under placebo were strongly associated with both self-reported and laboratory alcohol consumption, yet bias following alcohol administration did not predict either measure of consumption. These findings suggest that attentional bias is strongest before a drinking episode begins. As such, an attentional bias might be most influential in terms of initiation of alcohol consumption, and less of a factor in promoting continued consumption within the drinking episode. PMID:22732051

  5. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

    PubMed Central

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-01-01

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  6. Selective CRF2 receptor agonists ameliorate the anxiety- and depression-like state developed during chronic nicotine treatment and consequent acute withdrawal in mice.

    PubMed

    Bagosi, Zsolt; Palotai, Miklós; Simon, Balázs; Bokor, Péter; Buzás, András; Balangó, Beáta; Pintér, Dávid; Jászberényi, Miklós; Csabafi, Krisztina; Szabó, Gyula

    2016-12-01

    The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution. After 30min the mice were observed in an elevated plus-maze test or a forced swim test, for anxiety- and depression-like behavior. After 5min of testing, the plasma corticosterone concentration reflecting the activity of the hypothalamic-pituitary-adrenal (HPA) axis was also determined by a chemo-fluorescent method. Half of the animals were treated ICV and evaluated on the 8th day, the other half on the 9th day. On the 8th day, nicotine-treated mice presented signs of anxiolysis and depression, but no significant elevation of the plasma corticosterone concentration. On the 9th day, nicotine-treated mice exhibited signs of anxiety and depression and a significant increase of the plasma corticosterone levels. Central administration of UCN 2 or UCN 3 ameliorated the anxiety- and depression-like state including the hyperactivity of the HPA axis, developed during acute withdrawal following chronic nicotine treatment. The present study suggests that selective CRF2 receptor agonists could be used as a therapy in nicotine addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Severity of Acute Illness is Associated with Baseline Readiness to Change in Medical Intensive Care Unit Patients with Unhealthy Alcohol Use

    PubMed Central

    Clark, Brendan J.; Smart, Alexandra; House, Robert; Douglas, Ivor; Burnham, Ellen L.; Moss, Marc

    2011-01-01

    Introduction Unhealthy alcohol use predisposes to multiple conditions that frequently result in critical illness and is present in up to one-third of patients admitted to a medical intensive care unit (ICU). We sought to determine the baseline readiness to change in medical ICU patients with unhealthy alcohol use and hypothesized that the severity of acute illness would be independently associated with higher scores on readiness to change scales. We further sought to determine whether this effect is modified by the severity of unhealthy alcohol use. Materials and Methods We performed a cross-sectional observational study of current regular drinkers in three medical ICUs. The Alcohol Use Disorders Identification Test was used to differentiate low risk and unhealthy alcohol use and further categorize patients into risky alcohol use or an alcohol use disorder. The severity of a patient’s acute illness was assessed by calculating the Acute Physiology and Chronic Healthy Evaluation II score at the time of admission to the medical ICU. Readiness to change was assessed using standardized questionnaires. Results Of 101 medical ICU patients who were enrolled, 65 met the criteria for unhealthy alcohol use. The association between the severity of acute illness and readiness to change depended on the instrument used. A higher severity of illness measured by APACHEII score was an independent predictor of readiness to change as assessed by the Stages of Change Readiness and Treatment Eagerness Scale (Taking Action scale) (p< 0.01). When a visual analog scale was used to assess readiness to change, there was a significant association with severity of acute illness (p < 0.01) that was modified by the severity of unhealthy alcohol use (p = 0.04 for interaction term). Conclusion Medical ICU patients represent a population where brief interventions require further study. Studies of brief intervention should account for the severity of acute illness and the severity of unhealthy

  8. Quantitative trait locus gene mapping: a new method for locating alcohol response genes.

    PubMed

    Crabbe, J C

    1996-01-01

    Alcoholism is a multigenic trait with important non-genetic determinants. Studies with genetic animal models of susceptibility to several of alcohol's effects suggest that several genes contributing modest effects on susceptibility (Quantitative Trait Loci, or QTLs) are important. A new technique of QTL gene mapping has allowed the identification of the location in mouse genome of several such QTLs. The method is described, and the locations of QTLs affecting the acute alcohol withdrawal reaction are described as an example of the method. Verification of these QTLs in ancillary studies is described and the strengths, limitations, and future directions to be pursued are discussed. QTL mapping is a promising method for identifying genes in rodents with the hope of directly extrapolating the results to the human genome. This review is based on a paper presented at the First International Congress of the Latin American Society for Biomedical Research on Alcoholism, Santiago, Chile, November 1994.

  9. Determinants of improvement in quality of life of alcohol-dependent patients during an inpatient withdrawal programme

    PubMed Central

    Lahmek, Pierre; Berlin, Ivan; Michel, Laurent; Berghout, Chafia; Meunier, Nadine; Aubin, Henri-Jean

    2009-01-01

    Background: To investigate the improvement in quality of life (QoL) of alcohol-dependent patients during a 3-week inpatient withdrawal programme, and to identify the sociodemographic, clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment. Methods: This prospective, observational study included 414 alcohol-dependent patients, hospitalised for a period of 3 weeks. QoL was measured on admission and at discharge using the French version of the Medical Outcome Study SF-36. The mean scores for each dimension and for the Physical and Mental Component Summary scores were calculated. Results: The mean scores per dimension and the mean Physical and Mental Component Summary scores were significantly lower on admission than at discharge; the lowest scores being observed for social functioning and role limitations due to emotional problems. At discharge, the mean scores per dimension were similar to those observed in the French general population. Female gender, age >45 years, living alone, working as a labourer or employee, somatic comorbidity, and the existence of at least five criteria for alcohol dependence according to the DSM-IV classification were associated with a low Physical Component Summary score on admission; psychiatric comorbidity, the presence of at least five DSM-IV dependence criteria, smoking and suicidality were associated with a low Mental Component Summary score on admission. The increase in Physical and Mental Component Summary scores during hospitalisation was more marked when the initial scores were low. Apart from the initial score, the greatest improvement in Physical Component Summary score was seen in patients with a high alcohol intake and in those without a somatic comorbidity; the increase in Mental Component Summary score was greatest in patients without psychotic symptoms and in those who abused or were dependent on illegal drugs. Conclusion: QoL improvement

  10. Determinants of improvement in quality of life of alcohol-dependent patients during an inpatient withdrawal programme.

    PubMed

    Lahmek, Pierre; Berlin, Ivan; Michel, Laurent; Berghout, Chafia; Meunier, Nadine; Aubin, Henri-Jean

    2009-05-18

    To investigate the improvement in quality of life (QoL) of alcohol-dependent patients during a 3-week inpatient withdrawal programme, and to identify the sociodemographic, clinical and alcohol-related variables associated with baseline QoL on admission and with improvement of QoL during residential treatment. This prospective, observational study included 414 alcohol-dependent patients, hospitalised for a period of 3 weeks. QoL was measured on admission and at discharge using the French version of the Medical Outcome Study SF-36. The mean scores for each dimension and for the Physical and Mental Component Summary scores were calculated. The mean scores per dimension and the mean Physical and Mental Component Summary scores were significantly lower on admission than at discharge; the lowest scores being observed for social functioning and role limitations due to emotional problems. At discharge, the mean scores per dimension were similar to those observed in the French general population. Female gender, age > 45 years, living alone, working as a labourer or employee, somatic comorbidity, and the existence of at least five criteria for alcohol dependence according to the DSM-IV classification were associated with a low Physical Component Summary score on admission; psychiatric comorbidity, the presence of at least five DSM-IV dependence criteria, smoking and suicidality were associated with a low Mental Component Summary score on admission. The increase in Physical and Mental Component Summary scores during hospitalisation was more marked when the initial scores were low. Apart from the initial score, the greatest improvement in Physical Component Summary score was seen in patients with a high alcohol intake and in those without a somatic comorbidity; the increase in Mental Component Summary score was greatest in patients without psychotic symptoms and in those who abused or were dependent on illegal drugs. QoL improvement after a residential treatment was related to

  11. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... Reilly, M.T.; et al. Mpdz is a quantitative trait gene for drug withdrawal seizures. Nature Neuroscience 7(7):699–700, 2014. PMID: 15208631 . 12 Hurley, T.D., and Edenberg, H.J. Genes encoding enzymes involved in ethanol metabolism. Alcohol Research & Health 34:339–344, 2012 13 Yokoyama, A.; ...

  12. Acute tolerance to behavioral impairment by alcohol in moderate and heavy drinkers

    DOT National Transportation Integrated Search

    1974-04-01

    The literature reports greater impairment effects of a given Blood Alcohol Concentration (BAC) during the rising than during the falling BAC periods. This may be termed acute tolerance to contrast it with chronic tolerance built up over a long period...

  13. 27 CFR 28.28 - Withdrawal of wine and distilled spirits from customs bonded warehouses.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Withdrawal of wine and... Miscellaneous Provisions Customs Bonded Warehouses § 28.28 Withdrawal of wine and distilled spirits from customs bonded warehouses. Wine and bottled distilled spirits entered into customs bonded warehouses as provided...

  14. Acute Alcohol Effects on Narrative Recall and Contextual Memory: An Examination of Fragmentary Blackouts

    PubMed Central

    Wetherill, Reagan R.; Fromme, Kim

    2011-01-01

    The present study examined the effects of alcohol consumption on narrative recall and contextual memory among individuals with and without a history of fragmentary blackouts in an attempt to better understand why some individuals experience alcohol-induced memory impairments whereas others do not, even at comparable blood alcohol concentrations (BACs). Standardized beverage (alcohol, no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context memory performance before and after alcohol consumption in individuals with (n = 44) and without (n = 44) a history of fragmentary blackouts. Findings indicate acute alcohol intoxication led to impairments in free recall, but not next-day cued recall. Further, participants showed similar memory performance when sober, but individuals who consumed alcohol and had a positive history of fragmentary blackouts showed greater contextual memory impairments than those who had not previously experienced a fragmentary blackout. Thus, it appears that some individuals may have an inherent vulnerability to alcohol-induced memory impairments due to alcohol’s effects on contextual memory processes. PMID:21497445

  15. Persistent Adaptation by Chronic Alcohol is Facilitated by Neuroimmune Activation Linked to Stress and CRF

    PubMed Central

    Breese, George R.; Knapp, Darin J.

    2016-01-01

    This review updates the conceptual basis for the association of alcohol abuse with an insidious adaptation that facilitates negative affect during withdrawal from chronic intermittent alcohol (CIA) exposure – a change that later supports sensitization of stress-induced anxiety following alcohol abstinence. The finding that a CRF1-receptor antagonist (CRF1RA) minimized CIA withdrawal-induced negative affect supported an association of alcohol withdrawal with a stress mechanism. The finding that repeated stresses or multiple CRF injections into selected brain sites prior to a single 5-day chronic alcohol (CA) exposure induced anxiety during withdrawal provided critical support for a linkage of CIA withdrawal with stress. The determination that CRF1RA injection into positive CRF-sensitive brain sites prevented CIA withdrawal-induced anxiety provided support that neural path integration maintains the persistent CIA adaptation. Based upon reports that stress increases neuroimmune function, an effort was undertaken to test whether cytokines would support the adaptation induced by stress/CA exposure. Twenty-four hours after withdrawal from CIA, cytokine mRNAs were found to be increased in cortex as well as other sites in brain. Further, repeated cytokine injections into previously identified brain sites substituted for stress and CRF induction of anxiety during CA withdrawal. Discovery that a CRF1RA prevented the brain cytokine mRNA increase induced by CA withdrawal provided critical evidence for CRF involvement in this neuroimmune induction after CA withdrawal. However, the CRF1RA did not block the stress increase in cytokine mRNA increases in controls. The latter data supported the hypothesis that distinct mechanisms linked to stress and CA withdrawal can support common neuroimmune functions within a brain site. As evidence evolves concerning neural involvement in brain neuroimmune function, a better understanding of the progressive adaptation associated with CIA

  16. Effects of Acute Alcohol Tolerance on Perceptions of Danger and Willingness to Drive after Drinking

    PubMed Central

    Amlung, Michael T.; Morris, David H.; McCarthy, Denis M.

    2014-01-01

    Rationale Drinking and driving is associated with elevated rates of motor vehicle accidents and fatalities. Previous research suggests that alcohol impairs judgments about the dangers of risky behaviors; however, how alcohol affects driving-related judgments is less clear. Impairments have also been shown to differ across limbs of the blood alcohol concentration (BAC) curve, which is known as acute tolerance. Objectives Examine whether perceptions about the dangerousness of driving after drinking and willingness to drive differed across ascending and descending limbs of the BAC curve. Test whether reductions in perceived danger were associated with willingness to drive on the descending limb. Methods Fifty-six participants were randomly assigned to receive either a moderate dose of alcohol (peak BAC = 0.10 g%) or placebo. We assessed perceived dangerousness and willingness to drive at matched BACs (~0.067-0.068 g%) on the ascending and descending limbs. Results Both perceived danger and willingness to drive showed acute tolerance in the alcohol group. Participants judged driving to be significantly less dangerous and were more willing to drive on the descending limb compared to the ascending limb. The magnitude of change in perceived danger significantly predicted willingness to drive on the descending limb. Conclusions Decreased impairment associated with acute tolerance may lead individuals to underestimate the dangerousness of driving after drinking and in turn make poor decisions regarding driving. This study further emphasizes the descending limb as a period of increased risk and offers support for enhancing prevention efforts by targeting drivers at declining BAC levels. PMID:24752657

  17. Effects of acute alcohol tolerance on perceptions of danger and willingness to drive after drinking.

    PubMed

    Amlung, Michael T; Morris, David H; McCarthy, Denis M

    2014-11-01

    Drinking and driving is associated with elevated rates of motor vehicle accidents and fatalities. Previous research suggests that alcohol impairs judgments about the dangers of risky behaviors; however, how alcohol affects driving-related judgments is less clear. Impairments have also been shown to differ across limbs of the blood alcohol concentration (BAC) curve, which is known as acute tolerance. The objectives of this study were to examine whether perceptions about the dangerousness of driving after drinking and willingness to drive differed across the ascending and descending limbs of the BAC curve and to test whether reductions in perceived danger were associated with willingness to drive on the descending limb. Fifty-six participants were randomly assigned to receive either a moderate dose of alcohol (peak BAC = 0.10 g%) or placebo. We assessed perceived dangerousness and willingness to drive at matched BACs (~0.067-0.068 g%) on the ascending and descending limbs. Both perceived danger and willingness to drive showed acute tolerance in the alcohol group. Participants judged driving to be significantly less dangerous and were more willing to drive on the descending limb compared to the ascending limb. The magnitude of change in perceived danger significantly predicted willingness to drive on the descending limb. Decreased impairment associated with acute tolerance may lead individuals to underestimate the dangerousness of driving after drinking and in turn make poor decisions regarding driving. This study further emphasizes the descending limb as a period of increased risk and offers support for enhancing prevention efforts by targeting drivers at declining BAC levels.

  18. The effects of acute alcohol exposure on the response properties of neurons in visual cortex area 17 of cats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen Bo; State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Science, Beijing 100101; Xia Jing

    Physiological and behavioral studies have demonstrated that a number of visual functions such as visual acuity, contrast sensitivity, and motion perception can be impaired by acute alcohol exposure. The orientation- and direction-selective responses of cells in primary visual cortex are thought to participate in the perception of form and motion. To investigate how orientation selectivity and direction selectivity of neurons are influenced by acute alcohol exposure in vivo, we used the extracellular single-unit recording technique to examine the response properties of neurons in primary visual cortex (A17) of adult cats. We found that alcohol reduces spontaneous activity, visual evoked unitmore » responses, the signal-to-noise ratio, and orientation selectivity of A17 cells. In addition, small but detectable changes in both the preferred orientation/direction and the bandwidth of the orientation tuning curve of strongly orientation-biased A17 cells were observed after acute alcohol administration. Our findings may provide physiological evidence for some alcohol-related deficits in visual function observed in behavioral studies.« less

  19. Acute impact of caffeinated alcoholic beverages on cognition: A systematic review.

    PubMed

    Lalanne, Laurence; Lutz, Pierre-Eric; Paille, François

    2017-06-02

    Energy drinks are popular beverages that are supposed to counteract sleepiness, increase energy, maintain alertness and reduce symptoms of hangover. Cognitive enhancing seems to be related to many compounds such as caffeine, taurine and vitamins. Currently, users mostly combine psychostimulant effects of energy drinks to counteract sedative effects of alcohol. However, recent literature suggests that this combination conducts to feel less intoxicated but still impaired. The goal of the present article is to review cognitive impact and subjective awareness in case of caffeinated alcoholic beverage (CAB) intoxication. PubMed (January 1960 to March 2016) database was searched using the following terms: cognitive impairments, alcohol, energy drinks; cognition, alcohol, caffeine. 99 papers were found but only 12 randomized controlled studies which explored cognitive disorders and subjective awareness associated with acute CAB or AED (alcohol associated with energy drinks) intoxication were included. The present literature review confirmed that energy drinks might counteract some cognitive deficits and adverse effects of alcohol i.e. dry mouth, fatigue, headache, weakness, and perception of intoxication due to alcohol alone. This effect depends on alcohol limb but disappears when the complexity of the task increases, when driving for example. Moreover, studies clearly showed that CAB/AEDs increase impulsivity which conducts to an overconsumption of alcohol and enhanced motivation to drink compared to alcohol alone, potentiating the risk of developing addictive behaviors. This is a huge problem in adolescents with high impulsivity and immature decision making processes. Although energy drinks counteract some cognitive deficits due to alcohol alone, their association promotes the risk of developing alcohol addiction. As a consequence, it is necessary to better understand the neurobiological mechanisms underlying these interactions in order to better prevent the development

  20. Acute alcohol effects on narrative recall and contextual memory: an examination of fragmentary blackouts.

    PubMed

    Wetherill, Reagan R; Fromme, Kim

    2011-08-01

    The present study examined the effects of alcohol consumption on narrative recall and contextual memory among individuals with and without a history of fragmentary blackouts in an attempt to better understand why some individuals experience alcohol-induced memory impairments whereas others do not, even at comparable blood alcohol concentrations (BACs). Standardized beverage (alcohol and no alcohol) administration procedures and neuropsychological assessments measured narrative recall and context memory performance before and after alcohol consumption in individuals with (n=44) and without (n=44) a history of fragmentary blackouts. Findings indicate that acute alcohol intoxication led to impairments in free recall, but not next-day cued recall. Further, participants showed similar memory performance when sober, but individuals who consumed alcohol and had a positive history of fragmentary blackouts showed greater contextual memory impairments than those who had not previously experienced a fragmentary blackout. Thus, it appears that some individuals may have an inherent vulnerability to alcohol-induced memory impairments due to alcohol's effects on contextual memory processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.

    PubMed

    McBride, W J; Li, T K

    1998-01-01

    This review discusses efforts to develop rodent models for the study of neurobiological mechanisms underlying chronic alcohol drinking, alcoholism, and abnormal alcohol-seeking behavior. Selective breeding has produced stable lines of rats that reliably exhibit high and (for comparison purposes) low voluntary alcohol consumption. In addition, animal models of chronic ethanol self-administration have been developed in rodents, who do not have a genetic predisposition for high alcohol-seeking behavior, to explore environmental influences in ethanol drinking and the effects of physical dependence on alcohol self-administration. The selectively bred high-preference animals reliably self-administer ethanol by free-choice drinking and operantly respond for oral ethanol in amounts that produce pharmacologically meaningful blood alcohol concentrations (50 to 200 mg% and higher). In addition, the alcohol-preferring rats will self-administer ethanol by intragastric infusion. With chronic free-choice drinking, the high alcohol-preferring rats develop tolerance to the high-dose effects of ethanol and show signs of physical dependence after the withdrawal of alcohol. Compared with nonpreferring animals, the alcohol-preferring rats are less sensitive to the sedative-hypnotic effects of ethanol and develop tolerance more quickly to high-dose ethanol. Nonselected common stock rats can be trained to chronically self-administer ethanol following its initial presentation in a palatable sucrose or saccharin solution, and the gradual replacement of the sucrose or saccharin with ethanol (the sucrose/saccharin-fade technique). Moreover, rats that are trained in this manner and then made dependent by ethanol-vapor inhalation or liquid diet increase their ethanol self-administration during the withdrawal period. Both the selectively bred rats and common-stock rats demonstrate "relapse" and an alcohol deprivation effect following 2 or more weeks of abstinence. Systemic administration of

  2. Sex differences in acute relief of abstinence-induced withdrawal and negative affect due to nicotine content in cigarettes.

    PubMed

    Perkins, Kenneth A; Karelitz, Joshua L

    2015-04-01

    Acute cigarette smoking may relieve withdrawal and negative affect due to tobacco abstinence to a greater extent in women versus men. Yet, the relative contribution of the cigarette's nicotine content to this sex difference is not clear. Non-quitting dependent adult smokers (N = 44; 21 males, 23 females) participated in 2 virtually identical sessions, each after abstaining overnight (CO < 10 ppm) and differing only in the nicotine content of the designated cigarette. While blind to brand markings, they consumed a total of 24 puffs in controlled fashion for 2 hr in each session, either from a nicotine (Quest 1, 0.6 mg) or denicotinized (Quest 3, 0.05 mg) cigarette. Withdrawal symptoms were obtained before and after smoking, and negative affect was assessed after each period of cigarette exposure consisting of 6 puffs every 25 min. Men and women did not differ in baseline withdrawal and negative affect due to overnight abstinence, but reductions in each symptom were significantly influenced by the interaction of sex × nicotine/denicotinized cigarette (both p < .05). In men, but not in women, each symptom was generally decreased more by the nicotine versus denicotinized cigarette, and the nicotine cigarette reduced each to a greater degree in men versus women. Sex differences in relief of abstinence-induced withdrawal and negative affect due to the nicotine content in cigarettes are consistent with prior research indicating that nicotine per se, compared to non-nicotine smoke stimuli, is less rewarding in women versus men. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Adolescent smokers' response to reducing the nicotine content of cigarettes: Acute effects on withdrawal symptoms and subjective evaluations.

    PubMed

    Cassidy, Rachel N; Colby, Suzanne M; Tidey, Jennifer W; Jackson, Kristina M; Cioe, Patricia A; Krishnan-Sarin, Suchitra; Hatsukami, Dorothy

    2018-05-15

    Mandating a reduction in the nicotine content of cigarettes to a minimally addictive level could dramatically reduce smoking rates in the US. However, little is known about the effects of reduced nicotine content cigarettes in adolescents. Following overnight abstinence, adolescent daily smokers (ages 15-19, n = 50) reported on their craving, withdrawal, and positive and negative affect pre- and post- ad lib smoking of one cigarette containing varying nicotine content (15.8, 5.2, 1.3 and 0.4 mg/g of tobacco) in the laboratory and reported their subjective evaluations of each cigarette. Carbon monoxide (CO) boost from pre- to post-cigarette was calculated to determine if lower-nicotine cigarettes led to differential acute changes in toxicant exposure. All four nicotine cigarette types significantly reduced abstinence-induced craving, withdrawal, and negative affect (all p's < .05). Mixed models evaluating the effect of nicotine content, with nicotine dependence level and gender included as covariates, revealed a significant effect of nicotine content on craving and subjective evaluations: higher nicotine content resulted in greater reductions in craving and increases in both positive and negative subjective evaluations. There were no significant effects of nicotine dose on withdrawal symptoms, negative affect, or CO boost. These results suggest that lower nicotine cigarettes might result in reduced abuse liability compared to higher nicotine content cigarettes due to reduced positive subjective effects, while still reducing withdrawal, in adolescents. These results highlight the potential feasibility of this policy approach and support continued research on how a nicotine reduction policy may affect adolescent smoking patterns. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. An Anatomical Basis for Opponent Process Mechanisms of Opiate Withdrawal

    PubMed Central

    Radke, Anna K.; Rothwell, Patrick E.; Gewirtz, Jonathan C.

    2011-01-01

    Opponent process theory predicts that the first step in the induction of drug withdrawal is the activation of reward-related circuitry. Using the acoustic startle reflex as a model of anxiety-like behavior in rats, we show the emergence of a negative affective state during withdrawal after direct infusion of morphine into the ventral tegmental area (VTA), the origin of the mesolimbic dopamine system. Potentiation of startle during withdrawal from systemic morphine exposure requires a decrease in opiate receptor stimulation in the VTA and can be relieved by administration of the dopamine receptor agonist apomorphine. Together, our results suggest that the emergence of anxiety during withdrawal from acute opiate exposure begins with activation of VTA mesolimbic dopamine circuitry, providing a mechanism for the opponent process view of withdrawal. PMID:21593338

  5. Influence of the acute alcoholism on the phagocytic function of the mononuclear phagocytic system

    PubMed Central

    Sabino, KR; Petroianu, A; Alberti, LR

    2011-01-01

    Rationale:Alcoholics are more likely to have infections, mainly in the respiratory system. Alcohol seems to inhibit the immune system. Despite the extensive literature related to alcoholism, data related to the immune system are still not conclusive. Objective: The purpose of this study was to verify the influence of acute alcohol intake on colloid distribution in the organs of the mononuclear phagocyte system. Methods and Results: Thirteen male Swiss mice were divided into two groups: Group 1 (n = 5) – control, and Group 2 (n = 8) – animals that received 0.5 ml ethanol 50%, 30 minutes before the experiment. Colloidal sulphur labeled with ⁸⁸mTc was used to evaluate colloid distribution in the liver, spleen and lungs. Colloid clearance was assessed as well. A gamma camera was used to measure the radioactivity of these organs and of a blood clot. No difference was found in the presence of colloid in the organs of both groups. The liver showed the highest phagocytic intake, followed by the spleen and lungs (p = 0.021 for Group 1 and p = 0.003 for Group 2). A minimum amount of radiation remained in the blood of both groups. Discussion: According to the experiential conditions of this work, acute ingestion of alcohol did not interfere with the phagocytic function of the mononuclear phagocyte system in mice. PMID:22514578

  6. Diagnosis and Management of Alcoholic Liver Disease.

    PubMed

    Dugum, Mohannad; McCullough, Arthur

    2015-06-28

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

  7. Opioid interruptions, pain, and withdrawal symptoms in nursing home residents.

    PubMed

    Redding, Sarah E; Liu, Sophia; Hung, William W; Boockvar, Kenneth S

    2014-11-01

    Interruptions in opioid use have the potential to cause pain relapse and withdrawal symptoms. The objectives of this study were to observe patterns of opioid interruption during acute illness in nursing home residents and examine associations between interruptions and pain and withdrawal symptoms. Patients from 3 nursing homes in a metropolitan area who were prescribed opioids were assessed for symptoms of pain and withdrawal by researchers blinded to opioid dosage received, using the Brief Pain Inventory Scale and the Clinical Opioid Withdrawal Scale, respectively, during prespecified time periods. The prespecified time periods were 2 weeks after onset of acute illness (eg, urinary tract infection), and 2 weeks after hospital admission and nursing home readmission, if they occurred. Opioid dosing was recorded and a significant interruption was defined as a complete discontinuation or a reduction in dose of >50% for ≥1 day. The covariates age, sex, race, comorbid conditions, initial opioid dose, and initial pain level were recorded. Symptoms pre- and post-opioid interruptions were compared and contrasted with those in a group without opioid interruptions. Sixty-six patients receiving opioids were followed for a mean of 10.9 months and experienced a total of 104 acute illnesses. During 64 (62%) illnesses, patients experienced any reduction in opioid dosing, with a mean (SD) dose reduction of 63.9% (29.9%). During 39 (38%) illnesses, patients experienced a significant opioid interruption. In a multivariable model, residence at 1 of the 3 nursing homes was associated with a lower risk of interruption (odds ratio = 0.073; 95% CI, 0.009 to 0.597; P < 0.015). In patients with interruptions, there were statistically insignificant changes in mean (SD) pain score (difference -0.50 [2.66]; 95% CI, -3.16 to 2.16) and withdrawal score (difference -0.91 [3.12]; 95% CI, -4.03 to 2.21) after the interruption as compared with before interruption. However, when compared with

  8. Effects of Age and Acute Moderate Alcohol Administration on Electrophysiological Correlates of Working Memory Maintenance.

    PubMed

    Boissoneault, Jeff; Frazier, Ian; Lewis, Ben; Nixon, Sara Jo

    2016-09-01

    Previous studies suggest older adults may be differentially susceptible to the acute neurobehavioral effects of moderate alcohol intake. To our knowledge, no studies have addressed acute moderate alcohol effects on the electrophysiological correlates of working memory in younger and older social drinkers. This study characterized alcohol-related effects on frontal theta (FTP) and posterior alpha power (PAP) associated with maintenance of visual information during a working memory task. Older (55 to 70 years of age; n = 51, 29 women) and younger (25 to 35 years of age; n = 70, 39 women) community-dwelling moderate drinkers were recruited for this study. Participants were given either placebo or an active dose targeting breath alcohol concentrations (BrACs) of 0.04 or 0.065 g/dl. Following absorption, participants completed a visual working memory task assessing cue recognition following a 9-s delay. FTP and PAP were determined via Fourier transformation and subjected to 2 (age group) × 3 (dose) × 2 (repeated: working memory task condition) mixed models analysis. In addition to expected age-related reductions in PAP, a significant age group × dose interaction was detected for PAP such that 0.04 g/dl dose level was associated with greater PAP in younger adults but lower PAP in their older counterparts. PAP was lower in older versus younger adults at both active doses. Further mixed models revealed a significant negative association between PAP and working memory efficiency for older adults. No effects of age, dose, or their interaction were noted for FTP. Results bolster the small but growing body of evidence that older adults exhibit differential sensitivity to the neurobehavioral effects of moderate alcohol use. Given the theoretical role of PAP in attentional and working memory function, these findings shed light on the attentional mechanisms underlying effects of acute moderate alcohol on working memory efficiency in older adults. Copyright

  9. Reduced alcohol consumption in mice lacking preprodynorphin.

    PubMed Central

    Blednov, Yuri A.; Walker, Danielle; Martinez, Marni; Harris., R. Adron

    2007-01-01

    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the κ-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 hours) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest thath this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability). PMID:17307643

  10. Reduced alcohol consumption in mice lacking preprodynorphin.

    PubMed

    Blednov, Yuri A; Walker, Danielle; Martinez, Marni; Harris, R Adron

    2006-10-01

    Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the kappa-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 h) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin, but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild-type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference, or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest that this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

  11. [Aggression and restlessness following baclofen overdose: the narrow line between intoxication and withdrawal symptoms].

    PubMed

    de Witte, L D; Dekker, D; Veraart, J; Kromkamp, M; Kaasjager, K; Vinkers, C H

    2016-01-01

    Baclofen is increasingly prescribed for alcohol dependency. Subsequently, the risk of self-intoxication with this medicinal product is increasing. A 23-year-old man with a history of alcohol dependence was admitted to our hospital after self-intoxication with 2700 mg baclofen and 330 mg mirtazapine. Respiratory insufficiency as a result of the baclofen intoxication required intubation and admission to the ICU. During the first day, despite the use of sedatives, the patient became intermittently agitated and aggressive. In the following days, he developed severe delirium, probably due to baclofen withdrawal. The reintroduction of baclofen quickly resolved these symptoms. In the case of baclofen, in practice it is difficult to differentiate between intoxication and withdrawal. To prevent potentially severe withdrawal symptoms, we recommend reintroduction of baclofen when the first signs of restlessness and agitation arise following intoxication.

  12. Potential Biomarker Peptides Associated with Acute Alcohol-Induced Reduction of Blood Pressure

    PubMed Central

    Wakabayashi, Ichiro; Marumo, Mikio; Nonaka, Daisuke; Shimomura, Tomoko; Eguchi, Ryoji; Lee, Lyang-Ja; Tanaka, Kenji; Hatake, Katsuhiko

    2016-01-01

    The purpose of this study was to explore the peptides that are related to acute reduction of blood pressure after alcohol drinking. Venous blood was collected from male healthy volunteers before and after drinking white wine (3 ml/kg weight) containing 13% of ethanol. Peptidome analysis for serum samples was performed using a new target plate, BLOTCHIP®. Alcohol caused significant decreases in systolic and diastolic blood pressure levels at 45 min. The peptidome analysis showed that the levels of three peptides of m/z 1467, 2380 and 2662 changed significantly after drinking. The m/z 1467 and 2662 peptides were identified to be fragments of fibrinogen alpha chain, and the m/z 2380 peptide was identified to be a fragment of complement C4. The intensities of the m/z 2380 and m/z 1467 peptides before drinking were associated with % decreases in systolic and diastolic blood pressure levels at 45 min after drinking compared with the levels before drinking, while there were no significant correlations between the intensity of the m/z 2662 peptide and % decreases in systolic and diastolic blood pressure levels after drinking. The m/z 1467 and 2380 peptides are suggested to be markers for acute reduction of blood pressure after drinking alcohol. PMID:26815288

  13. Gender Differences in Acute Alcohol Effects on Self-Regulation of Arousal in Response to Emotional and Alcohol-Related Picture Cues

    PubMed Central

    Udo, Tomoko; Bates, Marsha E.; Mun, Eun Young; Vaschillo, Evgeny G.; Vaschillo, Bronya; Lehrer, Paul; Ray, Suchismita

    2010-01-01

    Basic mechanisms through which men and women self-regulate arousal have received little attention in human experimental addiction research although stress-response-dampening and craving theories suggest an important role of emotional arousal in motivating alcohol use. This study examined gender differences in the effects of acute alcohol intoxication on psychophysiological and self-reported arousal in response to emotionally negative, positive, and neutral, and alcohol-related, picture cues. Thirty-six social drinkers (16 women) were randomly assigned to an alcohol, placebo, or control beverage group, and exposed to picture cues every 10 s (0.1 Hz presentation frequency). Psychophysiological arousal was assessed via a 0.1-Hz heart rate variability (HRV) index. A statistically significant beverage group-by-gender interaction effect on psychophysiological, but not self-reported, arousal was found. 0.1-Hz HRV responses to picture cues were suppressed by alcohol only in men. This gender-specific suppression pattern did not differ significantly across picture cue types. There were no significant gender differences in the placebo or control group. Greater dampening of arousal by alcohol intoxication in men, compared to women, may contribute to men's greater tendency to use alcohol to cope with stress. PMID:19586136

  14. Intrathecal baclofen withdrawal: A rare cause of reversible cardiomyopathy.

    PubMed

    Awuor, Stephen O; Kitei, Paul M; Nawaz, Yassir; Ahnert, Amy M

    2016-03-01

    Baclofen is commonly used to treat spasticity of central etiology. Unfortunately, a potentially lethal withdrawal syndrome can complicate its use. This is especially true when the drug is administered intrathecally. There are very few cases of baclofen withdrawal leading to reversible cardiomyopathy described in the literature. The authors present a patient with a history of chronic intrathecal baclofen use who, in the setting of acute baclofen withdrawal, develops laboratory, electrocardiogram, and echocardiogram abnormalities consistent with cardiomyopathy. Upon reinstitution of intrathecal baclofen, the cardiomyopathy and associated abnormalities quickly resolve. Although rare, it is crucial to be aware of this reversible cardiomyopathy to ensure its prompt diagnosis and treatment.

  15. Narp regulates long-term aversive effects of morphine withdrawal

    PubMed Central

    Reti, Irving M.; Crombag, Hans S.; Takamiya, Kogo; Sutton, Jeffrey M.; Guo, Ning; Dinenna, Megan L.; Huganir, Richard L.; Holland, Peter C.; Baraban, Jay M.

    2008-01-01

    Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. As Narp is an immediate early gene product that is secreted at synaptic sites and binds to AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, we found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, we evaluated whether long-term aversive effects of morphine withdrawal are altered in Narp KO mice. We found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than WT controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. PMID:18729628

  16. Does retigabine affect the development of alcohol dependence?--A pharmaco-EEG study.

    PubMed

    Zwierzyńska, Ewa; Andrzejczak, Dariusz; Pietrzak, Bogusława

    2016-01-12

    New antiepileptic drugs have been investigated for their potential role in the treatment of alcohol dependence. One of these drugs is retigabine and this study examines the effect of retigabine co-administered with ethanol on the development of alcohol dependence and the course of acute withdrawal syndrome. A pharmaco-EEG method was used to examine this impact in selected brain structures of rabbits (midbrain reticular formation, hippocampus and frontal cortex). Retigabine was administered p.o. at a dose of 5mg/kg/day with ethanol ad libitum for 6 weeks and then alone for 2 weeks during an abstinence period. Changes in bioelectric activity, which demonstrated the inhibitory effect of alcohol on the brain structures, were already visible after 2 weeks of ethanol administration. In the abstinence period, changes were of a different nature and significant neuronal hyperactivity was observed, particularly in the midbrain reticular formation and the hippocampus. This findings reveal that retigabine decreased ethanol-induced changes during both alcohol administration and abstinence periods. In particular, the modulatory effect of retigabine on the hippocampus may be a significant element of its mechanism of action in alcohol dependence therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Assessment of affective and somatic signs of ethanol withdrawal in C57BL/6J mice using a short-term ethanol treatment.

    PubMed

    Perez, E E; De Biasi, M

    2015-05-01

    Alcohol is one of the most prevalent addictive substances in the world. Withdrawal symptoms result from abrupt cessation of alcohol consumption in habitual drinkers. The emergence of both affective and physical symptoms produces a state that promotes relapse. Mice provide a preclinical model that could be used to study alcohol dependence and withdrawal while controlling for both genetic and environmental variables. The use of a liquid ethanol diet offers a reliable method for the induction of alcohol dependence in mice, but this approach is impractical when conducting high-throughput pharmacological screens or when comparing multiple strains of genetically engineered mice. The goal of this study was to compare withdrawal-associated behaviors in mice chronically treated with a liquid ethanol diet vs. mice treated with a short-term ethanol treatment that consisted of daily ethanol injections containing the alcohol dehydrogenase inhibitor, 4-methylpyrazole. Twenty-four hours after ethanol treatment, mice were tested in the open field arena, the elevated plus maze, the marble burying test, or for changes in somatic signs during spontaneous ethanol withdrawal. Anxiety-like and compulsive-like behaviors, as well as physical signs, were all significantly elevated in mice undergoing withdrawal, regardless of the route of ethanol administration. Therefore, a short-term ethanol treatment can be utilized as a screening tool for testing genetic and pharmacological agents before investing in a more time-consuming ethanol treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 27 CFR 19.420 - Withdrawals of spirits without payment of tax for experimental or research use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Withdrawals of spirits without payment of tax for experimental or research use. A scientific university, college of learning, or institution of scientific research qualified under § 19.35 may withdraw spirits... without payment of tax for experimental or research use. 19.420 Section 19.420 Alcohol, Tobacco Products...

  19. [Effect of flavonoids of ginkgo biloba on anti-oxidizing system of mice after acute alcohol administration].

    PubMed

    Yao, Ping; Liu, Lie-Gang; Jia, Wen-Bo; Song, Fang-Fang; Zhou, Shaoliang; Zhang, Xiping; Sun, Xiufa

    2005-05-01

    To investigate the protective effects of flavonoids of ginkgo biloba on anti-oxidizing system damaged by acute alcohol administration. Adult male Kunming mice were employed and divided into randomly flavonoid intervention group, normal control and ethanol control group according to body weight. After pretreated with flavonoids of ginkgo biloba (96mg/kg bw), the mice in flavonoid intervention group ingested alcohol (ethanol 4.8g/kg bw) via i.g. and were decapitated after 0.5, 1, 2, 4, 6, 9, and 15 h of ethanol administration. The same treatment was carried out on ethanol control group except that physiological saline was applied instead of flavonoid of ginkgo biloba. Meanwhile, the normal control group was established. The concentration of glutathione (GSH), malondialdehyde (MDA) and the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) in the serum and liver were determined. The experiment displays that the content of GSH and the activities of GSH-Px and SOD decreased rapidly after 1 h of treatment with alcohol and dropped to the lowest level at 4h of treatment. After 6h of treatment, these indexes came to the normal level rapidly. The level of MDA of serum and liver increased rapidly after 1 h of treatment and reached the climax at 4h and 6h respectively. It went back to the normal concentration until 15h and 9 h respectively. On a whole, there were similar curves between flavonoids intervention group and alcohol control group on the indexes. However, to some extent, the supplement of flavonoid of ginkgo biloba can prohibit the rise of MDA level and the decline of GSH-Px, SOD, GSH which were induced by acute alcohol intakes. Flavonoid of ginkgo biloba have some protective effects on the damage of anti-oxidizing system of mice induced by acute alcohol adminstration.

  20. Alcohol-induced tolerance and physical dependence in mice with ethanol insensitive α1 GABAA receptors

    PubMed Central

    Werner, David F.; Swihart, Andrew R.; Ferguson, Carolyn; Lariviere, William R.; Harrison, Neil L.; Homanics, Gregg E.

    2009-01-01

    Background Although many people consume alcohol (ethanol), it remains unknown why some become addicted. Elucidating the molecular mechanisms of tolerance and physical dependence (withdrawal) may provide insight into alcohol addiction. While the exact molecular mechanisms of ethanol action are unclear, γ-aminobutyric acid type A receptors (GABAA-Rs) have been extensively implicated in ethanol action. The α1 GABAA-R subunit is associated with tolerance and physical dependence, but its exact role remains unknown. In this report, we tested the hypothesis that α1-GABAA-Rs mediate in part these effects of ethanol. Methods Ethanol-induced behavioral responses related to tolerance and physical dependence were investigated in knockin mice that have ethanol-insensitive α1 GABAA-Rs and wildtype controls. Acute functional tolerance (AFT) was assessed using the stationary dowel and loss of righting reflex assays. Chronic tolerance was assessed on the loss of righting reflex, fixed speed rotarod, hypothermia, and radiant tail flick assays following ten consecutive days of ethanol exposure. Withdrawal-related hyperexcitability was assessed by handling-induced convulsions following 3 cycles of ethanol vapor exposure/withdrawal. Immunoblots were used to assess α1 protein levels. Results Compared to controls, knockin mice displayed decreased AFT and chronic tolerance to ethanol-induced motor ataxia, and also displayed heightened ethanol-withdrawal hyperexcitability. No differences between wildtype and knockin mice were seen in other ethanol-induced behavioral measures. Following chronic exposure to ethanol, control mice displayed reductions in α1 protein levels, but knockins did not. Conclusions We conclude that α1-GABAA-Rs play a role in tolerance to ethanol-induced motor ataxia and withdrawal-related hyperexcitability. However, other aspects of behavioral tolerance and physical dependence do not rely on α1-containing GABAA-Rs. PMID:19032579

  1. Acute effects of alcohol on feedback processing and outcome evaluation during risky decision-making: an ERP study.

    PubMed

    Euser, Anja S; van Meel, Catharina S; Snelleman, Michelle; Franken, Ingmar H A

    2011-09-01

    Although risky decision-making is one of the hallmarks of alcohol use disorders, relatively little is known about the acute psychopharmacological effects of alcohol on decision-making processes. The present study investigated the acute effects of alcohol on neural mechanisms underlying feedback processing and outcome evaluation during risky decision-making, using event-related brain potentials (ERPs). ERPs elicited by positive and negative feedback were recorded during performance of a modified version of the Balloon Analogue Risk Task in male participants receiving either a moderate dose of alcohol (0.65 g/kg alcohol; n = 32) or a non-alcoholic placebo beverage (n = 32). Overall, there was no significant difference in the mean number of pumps between the alcohol and the placebo condition. However, when analyzing over time, it was found that the alcohol group made more riskier choices at the beginning of the task than the placebo group. ERPs demonstrated that alcohol consumption did not affect early processing of negative feedback, indexed by the feedback-related negativity. By contrast, alcohol-intoxicated individuals showed significantly reduced P300 amplitudes in response to negative feedback as compared to sober controls, suggesting that more elaborate evaluation to losses was significantly diminished. These results suggest that alcohol consumption does not influence the ability to rapidly evaluate feedback valence, but rather the ability to assign sufficient attention to further process motivationally salient outcomes. Blunted P300 amplitudes may reflect poor integration of feedback across trials, particularly adverse ones. Consequently, alcohol may keep people from effectively predicting the probability of future gains and losses based on their reinforcement history.

  2. Acute alcohol impairs conditioning of a behavioural reward-seeking response and inhibitory control processes--implications for addictive disorders.

    PubMed

    Loeber, Sabine; Duka, Theodora

    2009-12-01

    To investigate whether acute alcohol would affect performance of a conditioned behavioural response to obtain a reward outcome and impair performance in a task measuring inhibitory control to provide new knowledge of how the acute effects of alcohol might contribute to the transition from alcohol use to dependence. A randomized controlled between-subjects design was employed. The laboratory of experimental psychology at the University of Sussex. Thirty-two light to moderate social drinkers recruited from the undergraduate and postgraduate population. After the administration of alcohol (0.8 g/kg) or placebo participants underwent an instrumental reward-seeking procedure, with abstract stimuli serving as S+ (always predicting a win of 10 pence) and S- (always predicting a loss of 10 pence). In addition, a Stop Signal task was administered before and after the administration of alcohol. Participants of the alcohol group performed the behavioural response to obtain the reward outcome more often than placebo subjects in trials associated with loss of money. This finding was observed, although alcohol was not affecting explicit knowledge of stimulus-response outcome contingencies and acquisition of conditioned attentional and emotional responses. In addition, alcohol increased Stop Signal reaction time indicating disinhibiting effects of alcohol, and this was associated positively with response probability to the S-. These results demonstrate that alcohol is affecting inhibitory control of behavioural responses to external signals even when associated with punishment, contributing in this way to the transition from alcohol use to dependence.

  3. Ibogaine interferes with motivational and somatic effects of naloxone-precipitated withdrawal from acutely administered morphine.

    PubMed

    Parke, Linda A; Burton, Page; McDonald, Robert V; Kim, Joseph A; Siegel, Shepard

    2002-02-01

    It has been reported that ibogaine interferes with somatic withdrawal reactions in rats chronically treated with morphine. The present experiments demonstrated that ibogaine also interferes with motivational withdrawal reactions and somatic withdrawal reactions in rats treated with morphine on only two occasions. On each of two conditioning trials, naloxone was administered 24 h following an injection of morphine. Four hours prior to each naloxone administration, rats were injected with either ibogaine or saline. In two experiments, ibogaine interfered with naloxone-precipitated withdrawal. In Experiment 1, ibogaine-treated rats displayed a weaker aversion to the withdrawal-paired chamber, and in Experiment 2, ibogaine-treated rats displayed fewer somatic withdrawal reactions than did saline treated rats.

  4. Effects of Age and Acute Moderate Alcohol Administration on Electrophysiological Correlates of Working Memory Maintenance

    PubMed Central

    Boissoneault, Jeff; Frazier, Ian; Lewis, Ben; Nixon, Sara Jo

    2016-01-01

    Background Previous studies suggest older adults may be differentially susceptible to the acute neurobehavioral effects of moderate alcohol intake. To our knowledge, no studies have addressed acute moderate alcohol effects on the electrophysiological correlates of working memory in younger and older social drinkers. This study characterized alcohol-related effects on frontal theta (FTP) and posterior alpha power (PAP) associated with maintenance of visual information during a working memory task. Methods Older (55–70 years of age; n = 51, 29 women) and younger (25–35 years of age; n = 70, 39 women) community-dwelling moderate drinkers were recruited for this study. Participants were given either placebo or an active dose targeting breath alcohol concentrations (BrACs) of 0.04 or 0.065 g/dL. Following absorption, participants completed a visual working memory task assessing cue recognition following a 9s delay. FTP and PAP were determined via Fourier transformation and subjected to 2 (age group) X 3 (dose) X 2 (repeated: working memory task condition) mixed models analysis. Results In addition to expected age-related reductions in PAP, a significant age group X dose interaction was detected for PAP such that 0.04 g/dL dose level was associated with greater PAP in younger adults but lower PAP in their older counterparts. PAP was lower in older vs younger adults at both active doses. Further mixed models revealed a significant negative association between PAP and working memory efficiency for older adults. No effects of age, dose, or their interaction were noted for FTP. Conclusions Results bolster the small but growing body of evidence that older adults exhibit differential sensitivity to the neurobehavioral effects of moderate alcohol use. Given the theoretical role of PAP in attentional and working memory function, these findings shed light on the attentional mechanisms underlying effects of acute moderate alcohol on working memory efficiency in older adults

  5. Gender differences in acute alcohol effects on self-regulation of arousal in response to emotional and alcohol-related picture cues.

    PubMed

    Udo, Tomoko; Bates, Marsha E; Mun, Eun Young; Vaschillo, Evgeny G; Vaschillo, Bronya; Lehrer, Paul; Ray, Suchismita

    2009-06-01

    Basic mechanisms through which men and women self-regulate arousal have received little attention in human experimental addiction research, although stress-response-dampening and craving theories suggest an important role of emotional arousal in motivating alcohol use. This study examined gender differences in the effects of acute alcohol intoxication on psychophysiological and self-reported arousal in response to emotionally negative, positive, and neutral, and alcohol-related, picture cues. Thirty-six social drinkers (16 women) were randomly assigned to an alcohol, placebo, or control beverage group and exposed to picture cues every 10 s (0.1 Hz presentation frequency). Psychophysiological arousal was assessed via a 0.1-Hz heart rate variability (HRV) index. A statistically significant beverage group-by-gender interaction effect on psychophysiological, but not self-reported, arousal was found. The 0.1-Hz HRV responses to picture cues were suppressed by alcohol only in men. This gender-specific suppression pattern did not differ significantly across picture cue types. There were no significant gender differences in the placebo or control group. Greater dampening of arousal by alcohol intoxication in men, compared with women, may contribute to men's greater tendency to use alcohol to cope with stress. Copyright (c) 2009 APA, all rights reserved.

  6. Thirst for living of alcoholic patients: medical care's experience.

    PubMed

    Augeraud, Emmanuel; Puertolas, Christian; Rouchon, Dominique

    2004-01-01

    The medical care lavished on terminal and on alcoholic patients leads us to observe an analogy between these two life paths. This raises a question: do links exist between these two conditions? We will present Mr. B's record with alcohol. Analysing alcohol withdrawal allows us to show that during withdrawal, after having experienced similar stages to those described by Kübler-Ross, the alcoholic patient is in a grieving process. When abstinent, Mr. B faces two possibilities: either the grief is incomplete and the drive towards alcohol leads him to die to life; or he remains abstinent, with the help sometimes of what we call 'support dyads'. All this presupposes that the initial stages of dying to alcohol, followed by a psychic work of dis-fusion, have been brought to a successful conclusion. Links do exist between these two life paths, in the sense that these stages enable them to face the major trauma of their lives, e.g. alcoholism and serious illness.

  7. Patients With Sentinel Acute Pancreatitis of Alcoholic Etiology are at Risk for Organ Failure and Pancreatic Necrosis: A Dual-Center Experience

    PubMed Central

    Easler, Jeffrey J.; de-Madaria, Enrique; Nawaz, Haq; Moya-Hoyo, Neftalí; Koutroumpakis, Efstratios; Rey-Riveiro, Mónica; Singh, Vijay P.; Acevedo-Piedra, Nelly G.; Whitcomb, David C.; Yadav, Dhiraj; Papachristou, Georgios I.

    2016-01-01

    Objectives Assess the relationship between alcoholic etiology, tobacco use and severe acute pancreatitis (SAP). Methods Smoking and alcohol exposure were recorded upon admission in a cohort of acute pancreatitis patients within the United States (U.S.). Patients with first, “sentinel” attack of acute pancreatitis (AP) were identified for analysis. Associations between alcohol, smoking and SAP were validated in an independent cohort of patients from Spain. Results U.S. cohort (n=222): Thirty-five% developed organ failure (OF), 35% Pancreatic Necrosis (PNec), and 7% died. OF (54% vs. 33%, p=0.03), PNec (62% vs. 31%, p=0.006), intensive care (ICU) admission (58% vs. 36%, p=0.03) and length of stay (LOS) (20 vs. 8 days, p= 0.007) were greater in alcoholic when compared to other etiologies. Spanish cohort (n=366): Similar differences in outcomes were also found with between alcoholic and non-alcoholic etiologies: OF (24% vs. 8%, p=0.001), PNec (38% vs. 14%, p<0.001), ICU admission (20% vs. 3%, p<0.001), and LOS (17 vs. 11 days, p=0.04). Multivariable analysis confirmed alcoholic etiology to be independently associated with OF and PNec in both cohorts. Conclusions Alcoholic etiology is independently associated with OF and PNec in patients with sentinel AP and is important when evaluating risk for severe disease in AP. PMID:27101573

  8. Palonosetron and Hydroxyzine Pre-treatment Reduces the Objective Signs of Experimentally-Induced Acute Opioid Withdrawal in Humans: A Double-Blinded, Randomized, Placebo-Controlled Crossover Study

    PubMed Central

    Erlendson, Matthew; D'Arcy, Nicole; Encisco, Ellen; Yu, Jeff; Rincon-Cruz, Lorena; Peltz, Gary; Clark, J. David

    2017-01-01

    Background Treatments for reducing opioid withdrawal are limited and prone to problematic side effects. Laboratory studies, clinical observations, and limited human trial data suggest 5-HT3-receptor antagonists and antihistamines may be effective. Objectives This double-blind, crossover, placebo-controlled study employing an acute physical dependence model evaluated whether (i) treatment with a 5-HT3-receptor antagonist (palonosetron) would reduce opioid withdrawal symptoms, and (ii) co-administration of an antihistamine (hydroxyzine) would enhance any treatment effect. Methods At timepoint T=0, healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either a) placebo, b) palonosetron IV (0.75 mg), or c) palonosetron IV (0.75 mg) and hydroxyzine PO (100 mg) in a crossover study design. This was followed at T=30 by intravenous morphine (10mg/70kg). At T=165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T=170, 180, respectively). Baseline measurements were recorded at T=-30 and T=-15. Results Comparison of average baseline OOWS scores with OOWS scores obtained fifteen minutes after naloxone was significant (p=0.0001). Scores from fifteen minutes post-naloxone infusion showed significant differences in OOWS scores between treatment groups: placebo, 3.7 ± 2.4; palonosetron, 1.5± 0.97; and palonosetron with hydroxyzine, 0.2 ± .1333. Conclusions Pretreatment with palonosetron significantly reduced many signs of experimental-induced opioid withdrawal. Co-administration with hydroxyzine further reduced opioid withdrawal severity. These results suggest that 5-HT3 receptor antagonists, alone or in combination with an antihistamine, may be useful in the treatment of opioid withdrawal. PMID:27712113

  9. Acute alcohol intoxication among adolescents-the role of the context of drinking.

    PubMed

    Grüne, Bettina; Piontek, Daniela; Pogarell, Oliver; Grübl, Armin; Groß, Cornelius; Reis, Olaf; Zimmermann, Ulrich S; Kraus, Ludwig

    2017-01-01

    This study aims (1) to describe the context of drinking among adolescents with acute alcohol intoxication (AAI) by gender, (2) to explore temporal changes in the context of drinking and (3) to analyse the association between the context of drinking and blood alcohol concentration (BAC). A retrospective chart review of 12- to 17-year-old inpatients with AAI (n = 1441) of the years 2000 to 2006 has been conducted in five participating hospitals in Germany. Gender differences in the context of drinking were tested with t test and chi 2 test. Differences over time were analysed using logistic regressions. Multivariate linear regression was used to predict BAC. Girls and boys differed in admission time, drinking situation, drinking occasion and admission context. No temporal changes in drinking situation and in admission to hospital from public locations or places were found. Higher BAC coincided with male gender and age. Moreover, BAC was higher among patients admitted to hospital from public places and lower among patients who drank for coping. The results suggest gender differences in the context of drinking. The context of drinking needs to be considered in the development and implementation of target group-specific prevention and intervention measures. What is known: • The context of drinking, e.g. when, where, why and with whom is associated with episodic heavy drinking among adolescents. What is new: • Male and female inpatients with acute alcohol intoxication differ with regards to the context of drinking, i.e. in admission time, drinking situation, drinking occasion and admission context. • Being admitted to hospital from public places is associated with higher blood alcohol concentration.

  10. Alcohol use disorders and current pharmacological therapies: the role of GABAA receptors

    PubMed Central

    Liang, Jing; Olsen, Richard W

    2014-01-01

    Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create large problems both for society and for the drinkers themselves. To date, no therapeutic can effectively solve these problems. Understanding the underlying mechanisms leading to AUD is critically important for developing effective and safe pharmacological therapies. Benzodiazepines (BZs) are used to reduce the symptoms of alcohol withdrawal syndrome. However, frequent use of BZs causes cross-tolerance, dependence, and cross-addiction to alcohol. The FDA-approved naltrexone and acamprosate have shown mixed results in clinical trials. Naltrexone is effective to treat alcohol dependence (decreased length and frequency of drinking bouts), but its severe side effects, including withdrawal symptoms, are difficult to overcome. Acamprosate showed efficacy for treating alcohol dependence in European trials, but two large US trials have failed to confirm the efficacy. Another FDA-approved medication, disulfiram, does not diminish craving, and it causes a peripheral neuropathy. Kudzu is the only natural medication mentioned by the National Institute on Alcohol Abuse and Alcoholism, but its mechanisms of action are not yet established. It has been recently shown that dihydromyricetin, a flavonoid purified from Hovenia, has unique effects on GABAA receptors and blocks ethanol intoxication and withdrawal in alcoholic animal models. In this article, we review the role of GABAA receptors in the treatment of AUD and currently available and potentially novel pharmacological agents. PMID:25066321

  11. Narp regulates long-term aversive effects of morphine withdrawal.

    PubMed

    Reti, Irving M; Crombag, Hans S; Takamiya, Kogo; Sutton, Jeffrey M; Guo, Ning; Dinenna, Megan L; Huganir, Richard L; Holland, Peter C; Baraban, Jay M

    2008-08-01

    Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction.

  12. Acute tolerance to alcohol impairment of behavioral and cognitive mechanisms related to driving: drinking and driving on the descending limb.

    PubMed

    Weafer, Jessica; Fillmore, Mark T

    2012-04-01

    Alcohol effects on behavioral and cognitive mechanisms influence impaired driving performance and decisions to drive after drinking (Barry 1973; Moskowitz and Robinson 1987). To date, research has focused on the ascending limb of the blood alcohol curve, and there is little understanding of how acute tolerance to impairment of these mechanisms might influence driving behavior on the descending limb. To provide an integrated examination of the degree to which alcohol impairment of motor coordination and inhibitory control contributes to driving impairment and decisions to drive on the ascending and descending limbs of the blood alcohol curve. Social-drinking adults (N = 20) performed a testing battery that measured simulated driving performance and willingness to drive, as well as mechanisms related to driving: motor coordination (grooved pegboard), inhibitory control (cued go/no-go task), and subjective intoxication. Performance was tested in response to placebo and a moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol concentrations: once on the ascending limb and again on the descending limb. Impaired motor coordination and subjective intoxication showed acute tolerance, whereas driving performance and inhibitory control showed no recovery from impairment. Greater motor impairment was associated with poorer driving performance under alcohol, and poorer inhibitory control was associated with more willingness to drive. Findings suggest that acute tolerance to impairment of motor coordination is insufficient to promote recovery of driving performance and that the persistence of alcohol-induced disinhibition might contribute to risky decisions to drive on the descending limb.

  13. Acute tolerance to alcohol impairment of behavioral and cognitive mechanisms related to driving: drinking and driving on the descending limb

    PubMed Central

    Weafer, Jessica

    2015-01-01

    Rationale Alcohol effects on behavioral and cognitive mechanisms influence impaired driving performance and decisions to drive after drinking (Barry 1973; Moskowitz and Robinson 1987). To date, research has focused on the ascending limb of the blood alcohol curve, and there is little understanding of how acute tolerance to impairment of these mechanisms might influence driving behavior on the descending limb. Objectives To provide an integrated examination of the degree to which alcohol impairment of motor coordination and inhibitory control contributes to driving impairment and decisions to drive on the ascending and descending limbs of the blood alcohol curve. Methods Social-drinking adults (N=20) performed a testing battery that measured simulated driving performance and willingness to drive, as well as mechanisms related to driving: motor coordination (grooved pegboard), inhibitory control (cued go/no-go task), and subjective intoxication. Performance was tested in response to placebo and a moderate dose of alcohol (0.65 g/kg) twice at comparable blood alcohol concentrations: once on the ascending limb and again on the descending limb. Results Impaired motor coordination and subjective intoxication showed acute tolerance, whereas driving performance and inhibitory control showed no recovery from impairment. Greater motor impairment was associated with poorer driving performance under alcohol, and poorer inhibitory control was associated with more willingness to drive. Conclusions Findings suggest that acute tolerance to impairment of motor coordination is insufficient to promote recovery of driving performance and that the persistence of alcohol-induced disinhibition might contribute to risky decisions to drive on the descending limb. PMID:21960182

  14. Steroid avoidance or withdrawal for kidney transplant recipients.

    PubMed

    Haller, Maria C; Royuela, Ana; Nagler, Evi V; Pascual, Julio; Webster, Angela C

    2016-08-22

    Steroid-sparing strategies have been attempted in recent decades to avoid morbidity from long-term steroid intake among kidney transplant recipients. Previous systematic reviews of steroid withdrawal after kidney transplantation have shown a significant increase in acute rejection. There are various protocols to withdraw steroids after kidney transplantation and their possible benefits or harms are subject to systematic review. This is an update of a review first published in 2009. To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients. We searched the Cochrane Kidney and Transplant Specialised Register to 15 February 2016 through contact with the Information Specialist using search terms relevant to this review. All randomised and quasi-randomised controlled trials (RCTs) in which steroids were avoided or withdrawn at any time point after kidney transplantation were included. Assessment of risk of bias and data extraction was performed by two authors independently and disagreement resolved by discussion. Statistical analyses were performed using the random-effects model and dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals. We included 48 studies (224 reports) that involved 7803 randomised participants. Of these, three studies were conducted in children (346 participants). The 2009 review included 30 studies (94 reports, 5949 participants). Risk of bias was assessed as low for sequence generation in 19 studies and allocation concealment in 14 studies. Incomplete outcome data were adequately addressed in 22 studies and 37 were free of selective reporting.The 48 included studies evaluated three different comparisons: steroid avoidance or withdrawal compared with steroid maintenance, and steroid avoidance compared with steroid withdrawal. For the adult studies there was no significant difference in patient mortality either in studies

  15. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

  16. 29 CFR 4219.11 - Withdrawal liability upon mass withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Withdrawal liability upon mass withdrawal. 4219.11 Section... Redetermination of Withdrawal Liability Upon Mass Withdrawal § 4219.11 Withdrawal liability upon mass withdrawal. (a) Initial withdrawal liability. The plan sponsor of a multiemployer plan that experiences a mass...

  17. Alcohol-Use Disorders in the Critically Ill Patient

    PubMed Central

    Jones, Drew G.; Sessler, Curtis N.; Zilberberg, Marya D.; Weaver, Michael F.

    2010-01-01

    Alcohol abuse and dependence, referred to as alcohol-use disorders (AUDs), affect 76.3 million people worldwide and account for 1.8 million deaths per year. AUDs affect 18.3 million Americans (7.3% of the population), and up to 40% of hospitalized patients have AUDs. This review discusses the development and progression of critical illness in patients with AUDs. In contrast to acute intoxication, AUDs have been linked to increased severity of illness in a number of studies. In particular, surgical patients with AUDs experience higher rates of postoperative hemorrhage, cardiac complications, sepsis, and need for repeat surgery. Outcomes from trauma are worse for patients with chronic alcohol abuse, whereas burn patients who are acutely intoxicated may not have worse outcomes. AUDs are linked to not only a higher likelihood of community-acquired pneumonia and sepsis but also a higher severity of illness and higher rates of nosocomial pneumonia and sepsis. The management of sedation in patients with AUDs may be particularly challenging because of the increased need for sedatives and opioids and the difficulty in diagnosing withdrawal syndrome. The health-care provider also must be watchful for the development of dangerous agitation and violence, as these problems are not uncommonly seen in hospital ICUs. Despite studies showing that up to 40% of hospitalized patients have AUDs, relatively few guidelines exist on the specific management of the critically ill patient with AUDs. AUDs are underdiagnosed, and a first step to improving patient outcomes may lie in systematically and accurately identifying AUDs. PMID:20923804

  18. Phenibut (β-Phenyl-γ-aminobutyric Acid) Dependence and Management of Withdrawal: Emerging Nootropics of Abuse.

    PubMed

    Ahuja, Tania; Mgbako, Ofole; Katzman, Caroline; Grossman, Allison

    2018-01-01

    This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.

  19. Impact of acute alcohol consumption on lethality of suicide methods.

    PubMed

    Park, C Hyung Keun; Yoo, Seong Ho; Lee, Jaewon; Cho, Sung Joon; Shin, Min-Sup; Kim, Eun Young; Kim, Se Hyun; Ham, Keunsoo; Ahn, Yong Min

    2017-05-01

    The influence of acute alcohol consumption on the factors related to suicide remains understudied. Thus, the present study investigated the relationship between blood alcohol content (BAC) and the lethality of suicide methods. Autopsy data on 315 South Korean suicide completers with a positive BAC were collected from a nationwide pool between May 2015 and November 2015, and the methods were dichotomised as suicide methods of low lethality (SMLL; drug/chemical overdose and sharp objects, n=67) and suicide methods of high lethality (SMHL; everything else, n=243). BAC at the time of autopsy and various suicide-related factors of these two groups were compared with logistic regression analyses. Compared to suicide completers with a BAC in the lowest range of 0.011-0.049%, suicide completers with a BAC in the range of 0.150-0.199% were more likely to use SMHL (odds ratio [OR]: 3.644, 95% confidence interval [CI]: 1.221-10.874). Additionally, the adoption of SMHL was significantly associated with the absence of a psychiatric illness (OR: 0.433, 95% CI: 0.222-0.843) and a younger age; the OR for high BAC among subjects in their 40s was 0.266 (95% CI: 0.083-0.856); in their 50s, 0.183 (95% CI: 0.055-0.615); and in their 60s, 0.057 (95% CI: 0.015-0.216). The relationship between BAC and suicide method lethality was represented by a bell-shaped pattern in which suicide methods of high lethality were more likely to be used by suicide completers with mid-range BAC levels. The increased impulsivity and impairments in particular executive functions, including planning and organization, associated with acute alcohol use may influence the selection of a particular suicide method based on its lethality. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Acute Effects of Alcohol on Encoding and Consolidation of Memory for Emotional Stimuli

    PubMed Central

    Weafer, Jessica; Gallo, David A.; De Wit, Harriet

    2016-01-01

    Objective: Acute doses of alcohol impair memory when administered before encoding of emotionally neutral stimuli but enhance memory when administered immediately after encoding, potentially by affecting memory consolidation. Here, we examined whether alcohol produces similar biphasic effects on memory for positive or negative emotional stimuli. Method: The current study examined memory for emotional stimuli after alcohol (0.8 g/kg) was administered either before stimulus viewing (encoding group; n = 20) or immediately following stimulus viewing (consolidation group; n = 20). A third group received placebo both before and after stimulus viewing (control group; n = 19). Participants viewed the stimuli on one day, and their retrieval was assessed exactly 48 hours later, when they performed a surprise cued recollection and recognition test of the stimuli in a drug-free state. Results: As in previous studies, alcohol administered before encoding impaired memory accuracy, whereas alcohol administered after encoding enhanced memory accuracy. Critically, alcohol effects on cued recollection depended on the valence of the emotional stimuli: Its memory-impairing effects during encoding were greatest for emotional stimuli, whereas its memory-enhancing effects during consolidation were greatest for emotionally neutral stimuli. Effects of alcohol on recognition were not related to stimulus valence. Conclusions: This study extends previous findings with memory for neutral stimuli, showing that alcohol differentially affects the encoding and consolidation of memory for emotional stimuli. These effects of alcohol on memory for emotionally salient material may contribute to the development of alcohol-related problems, perhaps by dampening memory for adverse consequences of alcohol consumption. PMID:26751358

  1. Affective and Neuroendocrine Effects of Withdrawal from Chronic, Long-Acting Opiate Administration

    PubMed Central

    Hamilton, Kathryn L.; Harris, Andrew C.; Gewirtz, Jonathan C.

    2013-01-01

    Although the long-acting opiate methadone is commonly used to treat drug addiction, relatively little is known about effects of withdrawal from this drug in preclinical models. The current study examined affective, neuroendocrine, and somatic signs of withdrawal from the longer-acting methadone derivative l-alpha-acetylmethydol (LAAM) in rats. Anxiety-like behavior during both spontaneous and antagonist-precipitated withdrawal was measured by potentiation of the startle reflex. Withdrawal elevated corticosterone and somatic signs and blunted circadian variations in baseline startle responding. In addition, fear to an explicit, Pavlovian conditioned stimulus (fear-potentiated startle) was enhanced. These data suggest that anxiety-like behavior as measured using potentiated startle responding does not emerge spontaneously during withdrawal from chronic opiate exposure – in contrast to withdrawal from acute drug exposure – but rather is manifested as exaggerated fear in response to explicit threat cues. PMID:24076207

  2. A case of posterior reversible encephalopathy syndrome associated with acute pancreatitis and chronic alcoholism.

    PubMed

    Baek, Hyun Seok; Lee, Se-Jin

    2015-01-01

    Posterior reversible encephalopathy syndrome (PRES) is known to be caused by a variety of clinical disorders. The authors encountered a case of PRES associated with acute pancreatitis and chronic alcoholism. A 49-year-old man presented with altered mental status. Magnetic resonance imaging (MRI) displayed vasogenic edema at the bilateral posterior temporal and parieto-occipital lobes and cerebellum. Laboratory tests and abdominal computed tomography (CT) revealed acute pancreatitis. The patient recovered completely, and follow-up brain MRI and abdominal CT exhibited resolution of the previous lesions. We suggest that acute pancreatitis might be an etiology of PRES. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Effects of acute alcohol intoxication on saccadic conflict and error processing.

    PubMed

    Marinkovic, Ksenija; Rickenbacher, Elizabeth; Azma, Sheeva; Artsy, Elinor; Lee, Adrian K C

    2013-12-01

    Flexible behavior optimization relies on cognitive control which includes the ability to suppress automatic responses interfering with relevant goals. Extensive evidence suggests that the anterior cingulate cortex (ACC) is the central node in a predominantly frontal cortical network subserving executive tasks. Neuroimaging studies indicate that the ACC is sensitive to acute intoxication during conflict, but such evidence is limited to tasks using manual responses with arbitrary response contingencies. The present study was designed to examine whether alcohol's effects on top-down cognitive control would generalize to the oculomotor system during inhibition of hardwired saccadic responses. Healthy social drinkers (N = 22) underwent functional magnetic resonance imaging (fMRI) scanning and eye movement tracking during alcohol (0.6 g/kg ethanol for men, 0.55 g/kg for women) and placebo conditions in a counterbalanced design. They performed visually guided prosaccades (PS) towards a target and volitional antisaccades (AS) away from it. To mitigate possible vasoactive effects of alcohol on the BOLD (blood oxygenation level-dependent) signal, resting perfusion was quantified with arterial spin labeling (ASL) and used as a covariate in the BOLD analysis. Saccadic conflict was subserved by a distributed frontoparietal network. However, alcohol intoxication selectively attenuated activity only in the ACC to volitional AS and erroneous responses. This study provides converging evidence for the selective ACC vulnerability to alcohol intoxication during conflict across different response modalities and executive tasks, confirming its supramodal, high-level role in cognitive control. Alcohol intoxication may impair top-down regulative functions by attenuating the ACC activity, resulting in behavioral disinhibition and decreased self-control.

  4. A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome.

    PubMed

    Girish, K; Vikram Reddy, K; Pandit, Lakshmi V; Pundarikaksha, H P; Vijendra, R; Vasundara, K; Manjunatha, R; Nagraj, Moulya; Shruthi, R

    2016-02-01

    Alcohol withdrawal syndrome (AWS) is a distressing condition, generally controlled by benzodiazepines (BZD's). Baclofen, a gamma-aminobutyric acid-B (GABAB) agonist, has also shown promising results in controlling AWS. As there are few studies comparing the efficacy and tolerability of chlordiazepoxide with baclofen, the present study was taken up. The objective of this study was to compare efficacy and tolerability of baclofen with chlordiazepoxide in uncomplicated AWS. Sixty subjects with uncomplicated AWS were randomized into two groups of 30 each, to receive baclofen (30 mg) or chlordiazepoxide (75 mg) in decremented fixed dose regime for 9 days. Clinical efficacy was assessed by Clinical Institute Withdrawal Assessment for Alcohol-Revised Scale (CIWA-Ar) and tolerability by the nature and severity of adverse events. Lorazepam was used as rescue medication. Secondary efficacy parameters were Clinical Global Impression scores, symptom-free days, and subject satisfaction as assessed by visual analog scale. This study was registered with Clinical Trial Registry-India (CTRI/2013/04/003588), also subsequently registered with WHO's ICTRP clinical trial portal. Both baclofen and chlordiazepoxide showed a consistent reduction in the total CIWA-Ar scores. However, chlordiazepoxide showed a faster and a more effective control of anxiety and agitation requiring lesser lorazepam supplementation, and also showed a better subject satisfaction compared to baclofen. Both the drugs showed good tolerability with mild self-limiting adverse events. The present study demonstrates that baclofen is not as good as chlordiazepoxide in the treatment of uncomplicated AWS. However, baclofen might be considered as an alternative. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  5. Mental health consequences of exercise withdrawal: A systematic review.

    PubMed

    Weinstein, Ali A; Koehmstedt, Christine; Kop, Willem J

    2017-11-01

    A sedentary lifestyle has been associated with mental health disorders. Many medical conditions result in the cessation of exercise, which may increase the risk of developing mental health problems. The purpose of this article is to systematically review the literature examining the effects of exercise withdrawal on mental health. Literature was searched using PubMed, PsycINFO, and SPORTdiscus for studies that experimentally manipulated the withdrawal of exercise and included mental health as outcome measure. A total of 19 studies met inclusion criteria (total N=689 with 385 individuals participating in an exercise withdrawal condition). Exercise withdrawal consistently resulted in increases in depressive symptoms and anxiety. Other mental health outcomes were investigated infrequently. Severe mental health issues requiring clinical intervention after experimentally controlled exercise withdrawal was rare. Heterogeneity in methods and outcomes was observed, especially in terms of the duration of exercise withdrawal (range 1 to 42days, median=7days), with stronger effects if exercise withdrawal exceeded 2weeks. Experimentally controlled exercise withdrawal has adverse consequences for mental health. These observations in healthy individuals may help to understand the onset of mental health problems in response to acute and chronic medical conditions associated with reduced physical activity. Future research is needed to investigate potential mechanisms explaining the adverse mental health consequences of cessation of exercise that will provide new targets for clinical interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The Proximal Effects of Acute Alcohol Consumption on Male-to-Female Aggression: A Meta-Analytic Review of the Experimental Literature

    PubMed Central

    Crane, Cory A.; Godleski, Stephanie A.; Przybyla, Sarahmona M.; Schlauch, Robert C.; Testa, Maria

    2015-01-01

    The current meta-analytic review examined the experimental literature to quantify the causal effect of acute alcohol consumption on self-reported and observed indicators of male-to-female general, sexual, and intimate partner aggression. Database and reference list searches yielded 22 studies conducted between 1981 and 2014 that met all criteria for inclusion and that were subjected to full text coding for analysis. Results detected a significant overall effect (d = .36), indicating that male participants who consumed alcohol evidenced greater aggressive behavior toward females while completing a subsequent laboratory aggression paradigm than male participants who received no alcohol. We found homogeneity across all categories of potential moderator variables. Results further indicated that alcohol resulted in comparable increases of male-to-female sexual (d = .32) and intimate partner (d = .45) aggression. Further research is required to draw meaningful conclusions about individual and situational factors that may interact with acute alcohol consumption to produce the highest levels of risk. PMID:26009568

  7. The Proximal Effects of Acute Alcohol Consumption on Male-to-Female Aggression: A Meta-Analytic Review of the Experimental Literature.

    PubMed

    Crane, Cory A; Godleski, Stephanie A; Przybyla, Sarahmona M; Schlauch, Robert C; Testa, Maria

    2016-12-01

    The current meta-analytic review examined the experimental literature to quantify the causal effect of acute alcohol consumption on self-reported and observed indicators of male-to-female general, sexual, and intimate partner aggression. Database and reference list searches yielded 22 studies conducted between 1981 and 2014 that met all criteria for inclusion and that were subjected to full text coding for analysis. Results detected a significant overall effect (d = .36), indicating that male participants who consumed alcohol evidenced greater aggressive behavior toward females while completing a subsequent laboratory aggression paradigm than male participants who received no alcohol. We found homogeneity across all categories of potential moderator variables. Results further indicated that alcohol resulted in comparable increases of male-to-female sexual (d = .32) and intimate partner (d = .45) aggression. Further research is required to draw meaningful conclusions about individual and situational factors that may interact with acute alcohol consumption to produce the highest levels of risk. © The Author(s) 2015.

  8. [Clinical Practice Guide for Early Detection, Diagnosis and Treatment of the Acute Intoxication Phase in Patients with Alcohol Abuse or Dependence: Part I: Screening, Early Detection and Risk Factors in Patients with Alcohol Abuse or Dependence].

    PubMed

    de la Espriella Guerrero, Ricardo; de la Hoz Bradford, Ana María; Gómez-Restrepo, Carlos; Zárate, Alina Uribe-Holguín; Menéndez, Miguel Cote; Barré, Michelle Cortés; Rentería, Ana María Cano; Hernández, Delia Cristina

    2012-12-01

    Worldwide, alcohol is the second most-used psychotropic substance and the third risk factor for early death and disability. Its noxious use is a world public health problem given its personal, labor, family, economic and social impact. 70 % of people under risk of having alcohol problems go undetected in medical practice, a fact that underlines the need for specific screening measures allowing early detection leading to timely treatment. This article presents evidence gathered by alcohol abuse and dependence screening as well as by risk factor identification and screening. It also presents evidence concerning withdrawal symptoms, delirium tremens and Wernicke's encephalopathy in order to promote early detection and timely treatment. Systematic revision of the evidence available together with an evaluation of pertinent guidelines found in literature so as to decide whether to adopt or adapt the existing recommendation for each question or to develop de novo recommendations. For de novo recommendations as well as those adapted, it was carried out an evidence synthesis, together with evidence tables and formulation of recommendations based on the evidence. Evidence was found and recommendations were made for the pertinent screening and search of risk factors, in order to perform a diagnosis and carry out a timely management of alcohol abuse, dependence and ensuing complications: withdrawal syndrome, delirium tremens and Wernicke's encephalopathy. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  9. A STUDY ON THE COPING BEHAVIOURS OF WIVES OF ALCOHOLICS

    PubMed Central

    Rao, T.S. Sathyanarayana; Kuruvilla, K.

    1992-01-01

    A study was conducted on 30 wives of alcoholics using Orford-Guthrie's ‘coping with drinking’ questionnaire. Tlie commonest coping behaviour reported was discord, avoidance, indulgence and fearful withdrawal while marital breakdown, taking special action, assertion and sexual withdrawal were least frequent. There was no significant correlation between the coping behaviours and the variables like duration of marriage, duration of husband’s alcoholism, socio-economic and educational status. Implications of these findings are discussed and a cross cultural comparison is made. PMID:21776145

  10. Modulation of alcohol preference by NMDA antagonists in male rats.

    PubMed

    Lamblin, F; Deuceuninck, D; De Witte, P

    1993-11-01

    Chronic alcoholization by alcohol inhalation was used to study the properties of magnesium, a non-competitive NMDA receptor antagonist, and CGP 39551, a competitive NMDA receptor antagonist, on behavioural dependence as estimated by the free-choice paradigm [alcohol 10% (v/v) vs. water], on the hypermotility after alcohol withdrawal, and finally on the cortical vascularization. The first experimental group received the drugs per os during the whole alcoholization period. Magnesium (20 mg/kg/day) decreased the alcohol dependence while CGP 39551 (5 and 10 mg/kg/day) increased, in a dose-dependent manner, the dependence to alcohol. A second group of animals received the same drugs at the same dosages, not simultaneously during chronic alcoholization, but immediately after alcoholization in one shot i.p. injection. In this case, rats receiving 5 mg/kg CGP 39551 never showed any dependence towards alcohol, while 10 mg/kg CGP 39551 or 20 mg/kg magnesium prolonged the number of days of alcohol dependence. These results thus indicate the close interaction between NMDA receptor function and dependence for alcohol. Magnesium had no effects on hypermotility, while CGP 39551-treated animals presented a decrease in the hypermotility observed after alcohol withdrawal. Neither drug affected the hypervascularization accompanying the chronic alcoholization.

  11. Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High or Low Ethanol Preference

    PubMed Central

    Lopez, Marcelo F.; Grahame, Nicholas J.; Becker, Howard C.

    2010-01-01

    Background Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptiblility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction by using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. Methods Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 hr/day) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hr after final ethanol (or air) exposure for 5 consecutive days. Results Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared to HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice

  12. Severe Carisoprodol Withdrawal After a 14-Year Addiction and Acute Overdose.

    PubMed

    Vo, Kathy T; Horng, Howard; Smollin, Craig G; Benowitz, Neal L

    2017-05-01

    Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat. We present a case of a 34-year-old man with a long history of carisoprodol abuse who was found unresponsive after having ingested 7.5 grams of carisoprodol. He was intubated and admitted to the intensive care unit. He was given propofol, dexmedetomidine, fentanyl, ketamine, lorazepam, midazolam, quetiapine, and haloperidol, some at high-dose infusions, before his agitation and ventilator asynchrony could be controlled. His improvement coincided with the addition of carisoprodol and phenobarbital to his treatment regimen. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Trends show increasing emergency department presentations for drug-related disorders and treatment. This case highlights an uncommon case of carisoprodol withdrawal that may be encountered by emergency physicians, and demonstrates that benzodiazepines may not be sufficient to suppress severe withdrawal symptoms. Treatment with carisoprodol and phenobarbital provided additional benefit and can be considered in cases of severe carisoprodol withdrawal. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Binge alcohol drinking elicits persistent negative affect in mice.

    PubMed

    Lee, Kaziya M; Coehlo, Michal; McGregor, Hadley A; Waltermire, Ryan S; Szumlinski, Karen K

    2015-09-15

    Cessation from chronic alcohol abuse often produces a dysphoric state that can persist into protracted withdrawal. This dysphoric state is theorized to function as a negative reinforcer that maintains excessive alcohol consumption and/or precipitates relapse in those struggling to abstain from alcohol. However, we know relatively little regarding the impact of cessation from binge drinking on behavioral measures of negative affect and related neurobiology. Male C57BL/6J mice were given access to unsweetened 20% alcohol for 6 weeks under modified Drinking-in-the-dark procedures, followed by behavioral testing beginning either 1 or 21 days into withdrawal. Mice were administered a behavioral test battery consisting of: the elevated plus maze, light/dark box, novel object test, marble burying test, Porsolt forced swim test and sucrose preference test to assess anxiogenic and depressive signs. Egr1 immunostaining was used to quantify cellular activity within the central nucleus of the amygdala (CEA), basolateral amygdala (BLA), bed nucleus of the stria terminalis (BNST), and the nucleus accumbens (Acb) shell (AcbSh) and core (AcbC). Compared to water controls, alcohol-drinking mice exhibited higher indices of emotionality in the majority of behavioral assays. The hyper-emotionality exhibited by binge drinking mice was apparent at both withdrawal time-points and correlated with higher Egr1+ cell counts in the CEA and BNST, compared to controls. These data show that affective symptoms emerge very early after cessation of binge drinking and persist into protracted withdrawal. A history of binge drinking is capable of producing enduring neuroadaptations within brain circuits mediating emotional arousal. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. The current situation of treatment systems for alcoholism in Korea.

    PubMed

    Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon; Choi, Ihn-Geun

    2013-02-01

    Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.

  15. The Current Situation of Treatment Systems for Alcoholism in Korea

    PubMed Central

    Kim, Jee Wook; Lee, Boung Chul; Kang, Tae-Cheon

    2013-01-01

    Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care. PMID:23400047

  16. Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal.

    PubMed

    Hughes, Robert N; Hancock, Nicola J

    2017-03-15

    For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence.

    PubMed

    Hashimoto, Joel G; Gavin, David P; Wiren, Kristine M; Crabbe, John C; Guizzetti, Marina

    2017-05-01

    Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitinationhylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study. Published by Elsevier

  18. Prefrontal cortex expression of chromatin modifier genes in male WSP and WSR mice changes across ethanol dependence, withdrawal, and abstinence

    PubMed Central

    Hashimoto, Joel G.; Gavin, David P.; Wiren, Kristine M.; Crabbe, John C.; Guizzetti, Marina

    2017-01-01

    Alcohol-use disorder (AUD) is a relapsing disorder associated with excessive ethanol consumption. Recent studies support the involvement of epigenetic mechanisms in the development of AUD. Studies carried out so far have focused on a few specific epigenetic modifications. The goal of this project was to investigate gene expression changes of epigenetic regulators that mediate a broad array of chromatin modifications after chronic alcohol exposure, chronic alcohol exposure followed by 8 h withdrawal, and chronic alcohol exposure followed by 21 days of abstinence in Withdrawal-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) selected mouse lines. We found that chronic vapor exposure to highly intoxicating levels of ethanol alters the expression of several chromatin remodeling genes measured by quantitative PCR array analyses. The identified effects were independent of selected lines, which, however, displayed baseline differences in epigenetic gene expression. We reported dysregulation in the expression of genes involved in histone acetylation, deacetylation, lysine and arginine methylation and ubiquitination, and in DNA methylation during chronic ethanol exposure and withdrawal, but not after 21 days of abstinence. Ethanol-induced changes are consistent with decreased histone acetylation and with decreased deposition of the permissive ubiquitination mark H2BK120ub, associated with reduced transcription. On the other hand, ethanol-induced changes in the expression of genes involved in histone lysine methylation are consistent with increased transcription. The net result of these modifications on gene expression is likely to depend on the combination of the specific histone tail modifications present at a given time on a given promoter. Since alcohol does not modulate gene expression unidirectionally, it is not surprising that alcohol does not unidirectionally alter chromatin structure toward a closed or open state, as suggested by the results of this study. PMID

  19. Glutamatergic targets for new alcohol medications

    PubMed Central

    Spanagel, Rainer; Krystal, John H.

    2013-01-01

    Rationale An increasingly compelling literature points to a major role for the glutamate system in mediating the effects of alcohol on behavior and the pathophysiology of alcoholism. Preclinical studies indicate that glutamate signaling mediates certain aspects of ethanol’s intoxicating and rewarding effects, and undergoes adaptations following chronic alcohol exposure that may contribute to the withdrawal, craving and compulsive drug-seeking that drive alcohol abuse and alcoholism. Objectives We discuss the potential for targeting the glutamate system as a novel pharmacotherapeutic approach to treating alcohol use disorders, focusing on five major components of the glutamate system: the N-methyl-D-aspartate (NMDA) receptor and specific NMDA subunits, the glycineB site on the NMDA receptors (NMDAR), L-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) and kainate (KAR) receptors, metabotropic receptors (mGluR), and glutamate transporters. Results Chronic alcohol abuse produces a hyperglutamatergic state, characterized by elevated extracellular glutamate and altered glutamate receptors and transporters. Pharmacologically manipulating glutamatergic neurotransmission alters alcohol-related behaviors including intoxication, withdrawal, and alcohol-seeking, in rodents and human subjects. Blocking NMDA and AMPA receptors reduces alcohol consumption in rodents, but side-effects may limit this as a therapeutic approach. Selectively targeting NMDA and AMPA receptor subunits (e.g., GluN2B, GluA3), or the NMDAR glycineB site offers an alternative approach. Blocking mGluR5 potently affects various alcohol-related behaviors in rodents, and mGluR2/3 agonism also suppresses alcohol consumption. Finally, glutamate transporter upregulation may mitigate behavioral and neurotoxic sequelae of excess glutamate caused by alcohol. Conclusions Despite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new

  20. Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine

    PubMed Central

    Fitzgerald, Paul J.

    2013-01-01

    A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general. PMID:24151426

  1. Serotonin's Complex Role in Alcoholism: Implications for Treatment and Future Research.

    PubMed

    Marcinkiewcz, Catherine A; Lowery-Gionta, Emily G; Kash, Thomas L

    2016-06-01

    Current pharmacological treatments for alcohol dependence have focused on reducing alcohol consumption, but to date there are few treatments that also address the negative affective symptoms during acute and protracted alcohol withdrawal which are often exacerbated in people with comorbid anxiety and depression. Selective serotonin reuptake inhibitors (SSRIs) are sometimes prescribed to ameliorate these symptoms but can exacerbate anxiety and cravings in a select group of patients. In this critical review, we discuss recent literature describing an association between alcohol dependence, the SERT linked polymorphic region (5-HTTLPR), and pharmacological response to SSRIs. Given the heterogeneity in responsiveness to serotonergic drugs across the spectrum of alcoholic subtypes, we assess the contribution of specific 5-HT circuits to discrete endophenotypes of alcohol dependence. 5-HT circuits play a distinctive role in reward, stress, and executive function which may account for the variation in response to serotonergic drugs. New optogenetic and chemogenetic methods for dissecting 5-HT circuits in alcohol dependence may provide clues leading to more effective pharmacotherapies. Although our current understanding of the role of 5-HT systems in alcohol dependence is incomplete, there is some evidence to suggest that 5-HT3 receptor antagonists are effective in people with the L/L genotype of the 5-HTTLPR polymorphism while SSRIs may be more beneficial to people with the S/L or S/S genotype. Studies that assess the impact of serotonin transporter polymorphisms on 5-HT circuit function and the subsequent development of alcohol use disorders will be an important step forward in treating alcohol dependence. Copyright © 2016 by the Research Society on Alcoholism.

  2. Disentangling contributions of bar attendance, drinking, and other factors to elevated acute alcohol problems on the U.S.-Mexico border.

    PubMed

    Mills, Britain A; Caetano, Raul; Vaeth, Patrice A C; Reingle Gonzalez, Jennifer M

    2015-11-01

    Levels of drinking are unusually elevated among young adults on the U.S.-Mexico border, and this elevation can be largely explained by young border residents' unusually high frequency of bar attendance. However, this explanation complicates interpretation of high alcohol problem rates that have also been observed in this group. Because bar environments can lower the threshold for many types of problems, the extent to which elevated alcohol problems among young border residents can be attributed to drinking per se-versus this common drinking context-is not clear. Data were collected from multistage cluster samples of adult Mexican Americans on and off the U.S.-Mexico border (current drinker N = 1,351). After developing structural models of acute alcohol problems, estimates were subjected to path decompositions to disentangle the common and distinct contributions of drinking and bar attendance to problem disparities on and off the border. Additionally, models were estimated under varying degrees of adjustment to gauge the sensitivity of the results to sociodemographic, social-cognitive, and environmental sources of confounding. Consistent with previous findings for both drinking and other problem measures, acute alcohol problems were particularly elevated among young adults on the border. This elevation was entirely explained by a single common pathway involving bar attendance frequency and drinking. Bar attendance did not predict acute alcohol problems independently of drinking, and its effect was not moderated by border proximity or age. The common indirect effect and its component effects (of border youth on bar attendance, of bar attendance on drinking, and of drinking on problems) were surprisingly robust to adjustment for confounding in all parts of the model (e.g., fully adjusted indirect effect: b = 0.11, SE = 0.04, p < 0.01). Bar attendance and associated increases in drinking play a key, unique role in the high levels of acute alcohol problems among the

  3. Withdrawal of statins increases event rates in patients with acute coronary syndromes.

    PubMed

    Heeschen, Christopher; Hamm, Christian W; Laufs, Ulrich; Snapinn, Steven; Böhm, Michael; White, Harvey D

    2002-03-26

    HMG-CoA Reductase Inhibitors (statins) reduce cardiac event rates in patients with stable coronary heart disease. Withdrawal of chronic statin treatment during acute coronary syndromes may impair vascular function independent of lipid-lowering effects and thus increase cardiac event rate. We investigated the effects of statins on the cardiac event rate in 1616 patients of the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study who had coronary artery disease and chest pain in the previous 24 hours. We recorded death and nonfatal myocardial infarction during the 30-day follow-up. Baseline clinical characteristics did not differ among 1249 patients without statin therapy, 379 patients with continued statin therapy, and 86 patients with discontinued statin therapy after hospitalization. Statin therapy was associated with a reduced event rate at 30-day follow-up compared with patients without statins (adjusted hazard ratio, 0.49 [95% CI, 0.21 to 0.86]; P=0.004). If the statin therapy was withdrawn after admission, cardiac risk increased compared with patients who continued to receive statins (2.93 [95% CI, 1.64 to 6.27]; P=0.005) and tended to be higher compared with patients who never received statins (1.69 [95% CI, 0.92 to 3.56]; P=0.15). This was related to an increased event rate during the first week after onset of symptoms and was independent of cholesterol levels. In a multivariate model, troponin T elevation (P=0.005), ST changes (P=0.02), and continuation of statin therapy (P=0.008) were the only independent predictors of patient outcome. Statin pretreatment in patients with acute coronary syndromes is associated with improved clinical outcome. However, discontinuation of statins after onset of symptoms completely abrogates this beneficial effect.

  4. Magnetic resonance imaging findings in substance abuse: alcohol and alcoholism and syndromes associated with alcohol abuse.

    PubMed

    Spampinato, M Vittoria; Castillo, Mauricio; Rojas, Rafael; Palacios, Enrique; Frascheri, Laura; Descartes, Fernando

    2005-06-01

    Alcohol abuse is common among the population and results in significant diseases that shorten life span. Ethanol may result in chronic brain changes such as atrophy but may also result in neurologic disease that may be acute or chronic and sometimes life threatening. Accompanying vitamin deficiencies may lead to Wernicke's encephalopathy and changes in serum osmosis may lead to several acute demyelinating disorders. In addition, pregnant women who consume alcohol place their babies at high risk for the fetal alcohol syndrome. In this article we review these disorders and emphasize their imaging features.

  5. Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system.

    PubMed

    Pfeifer, Philippe; Tüscher, Oliver; Buchholz, Hans Georg; Gründer, Gerhard; Vernaleken, Ingo; Paulzen, Michael; Zimmermann, Ulrich S; Maus, Stephan; Lieb, Klaus; Eggermann, Thomas; Fehr, Christoph; Schreckenberger, Mathias

    2017-09-01

    Investigations on the acute effects of alcohol in the human mesolimbic dopamine D 2 /D 3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D 2 /D 3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D 2 /D 3 receptor ligand [ 18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D 2 /D 3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underwent a standardized intravenous and placebo alcohol administration. The subjective effects of alcohol were measured with a visual analogue scale. For the evaluation of the dopamine response we calculated the binding potential (BP ND ) by using the simplified reference tissue model (SRTM). In addition, we calculated distribution volumes (target and reference regions) in 10 subjects for which metabolite corrected arterial samples were available. In the alcohol condition no significant dopamine response in terms of a reduction of BP ND was observed in striatal and extrastriatal brain regions. We found a positive correlation for 'liking' alcohol and the BP ND in extrastriatal brain regions (Inferior frontal cortex (IFC) (r = 0.533, p = 0.007), orbitofrontal cortex (OFC) (r = 0.416, p = 0.043) and prefrontal cortex (PFC) (r = 0.625, p = 0.001)). The acute alcohol effects on the D 2 /D 3 dopamine receptor binding potential of the striatal and extrastriatal system in our experiment were insignificant. A positive correlation of the subjective effect of 'liking' alcohol with cortical D 2 /D 3 receptors may hint at an addiction relevant trait. © 2016 Society for the Study of Addiction.

  6. Protective effect of Carica papaya L leaf extract against alcohol induced acute gastric damage and blood oxidative stress in rats.

    PubMed

    Indran, M; Mahmood, A A; Kuppusamy, U R

    2008-09-01

    The effects of Carica papaya leaf (CPL) aqueous extract on alcohol induced acute gastric damage and the immediate blood oxidative stress level were studied in rats. The results showed that gastric ulcer index was significantly reduced in rats pretreated with CPL extract as compared with alcohol treated controls. The in vitro studies using 2,2-Diphenyl-1-Picryl-Hydrazyl (DPPH) assay showed strong antioxidant nature of CPL extract. Biochemical analysis indicated that the acute alcohol induced damage is reflected in the alterations of blood oxidative indices and CPL extract offered some protection with reduction in plasma lipid peroxidation level and increased erythrocyte glutathione peroxidase activity. Carica papaya leaf may potentially serve as a good therapeutic agent for protection against gastric ulcer and oxidative stress.

  7. Acute effects of alcohol on memory: impact of emotional context and serial position.

    PubMed

    Brown, Jennie; Brignell, Catherine M; Dhiman, Sharinjeet K; Curran, H Valerie; Kamboj, Sunjeev K

    2010-03-01

    Although the amnestic effects of alcohol in humans are well known, its effects on emotional memory are unclear. In this study, using a randomized double-blind placebo-controlled design, we examine narrative emotional episodic memory in healthy human female volunteers (n=32) who received either a single dose of alcohol (0.6g/kg), or a placebo and then viewed neutral story elements presented in either a neutral or emotional context. Memory was tested for gist and detail of the neutral elements 3days later in a surprise recognition test. Since alcohol modulates GABAergic neurotransmission and may exert its effects on emotion through the limbic system, we predicted that acute alcohol treatment would reduce the expected emotional memory-advantage for gist, leaving detail memory relatively unaffected. Furthermore, given previous findings showing that 'primacy' memory is enhanced by physiological arousal, we predicted that reduced arousal produced by alcohol would have the opposite effect and impair primacy memory relative to the middle or 'recency' sections of the narrative. Emotional arousal was expected to oppose this effect, so impaired primacy memory following alcohol was only expected in the neutral version of the narrative. Although there was a main effect of story phase (though not of story version), contrary to expectations, alcohol impaired primacy memory for emotionally encoded neutral material. The results suggest that under certain circumstances emotional context or physiological arousal make memories labile and susceptible to disruption through pharmacological manipulation during encoding. 2009 Elsevier Inc. All rights reserved.

  8. Rodent Models of Genetic Contributions to Motivation to Abuse Alcohol

    PubMed Central

    Crabbe, John C.

    2016-01-01

    The distinction between alcohol use (normative) and abuse (unfortunately common) implies dysregulation of motivation directed toward the drug. Genetic contributions to abuse risk are mediated through personality differences, other predispositions to drink excessively, and differences in sensitivity to the acute and chronic consequences of the drug. How to assess motivation in laboratory animals is not straightforward but risk factors for and consequences of alcohol abuse can be modeled with reasonable fidelity in laboratory rodents. Remarkably few rodent studies focus on the genetic contributions to alcohol’s reinforcing value: almost all examine preferential drinking of unflavored alcohol over water. Such studies will likely never avoid the confounding role of taste preferences and most often yield intake levels insufficient to yield a pharmacologically significant blood alcohol level. Genotypes that avoid alcohol probably do so based on pre-ingestive sensory cues; however, post-ingestive consequences are also important. Thus, the quest for improved measures of reinforcing value continues. We have genetic differences aplenty, but still lack evidence that any genotype will readily self-administer alcohol to the devastating extent that many alcoholics will. Encouraging results that are emerging include improved behavioral methods for elevating alcohol intake and inferring alcohol reinforcement, as well as new genetic animal models. Several ingenious assays to index alcohol’s motivational effects have been used extensively. Alcoholic drinking that attempts to prevent or to alleviate withdrawal symptoms has been modeled. Another characteristic of alcoholic drinking is its persistence despite abundant evidence to the drinker of the damaging effects of the excessive drinking on work, relationships, and/or health. Modeling such persistence in rodents has been uncommon to date. New genetic animal models include lines of mice selectively bred for chronic high drinking

  9. Acute alcohol effects on set-shifting and its moderation by baseline individual differences: a latent variable analysis.

    PubMed

    Korucuoglu, Ozlem; Sher, Kenneth J; Wood, Phillip K; Saults, John Scott; Altamirano, Lee; Miyake, Akira; Bartholow, Bruce D

    2017-03-01

    To compare the acute effects of alcohol on set-shifting task performance (relative to sober baseline performance) during ascending and descending limb breath alcohol concentration (BrAC), as well as possible moderation of these effects by baseline individual differences. Shifting performance was tested during an initial baseline and a subsequent drinking session, during which participants were assigned randomly to one of three beverage conditions (alcohol, placebo or control) and one of two BrAC limb conditions [ascending and descending (A/D) or descending-only (D-only)]. A human experimental laboratory on the University of Missouri campus in Columbia, MO, USA. A total of 222 moderate-drinking adults (ages 21-30 years) recruited from Columbia, MO and tested between 2010 and 2013. The outcome measure was performance on set-shifting tasks under the different beverage and limb conditions. Shifting performance assessed at baseline was a key moderator. Although performance improved across sessions, this improvement was reduced in the alcohol compared with no-alcohol groups (post-drink latent mean comparison across groups, all Ps ≤ 0.05), and this effect was more pronounced in individuals with lower pre-drink performance (comparison of pre- to post-drink path coefficients across groups, all Ps ≤ 0.05). In the alcohol group, performance was better on descending compared with ascending limb (P ≤ 0.001), but descending limb performance did not differ across the A/D and D-only groups. Practising tasks before drinking moderates the acute effects of alcohol on the ability to switch between tasks. Greater impairment in shifting ability on descending compared with ascending breath alcohol concentration is not related to task practice. © 2016 Society for the Study of Addiction.

  10. Efficacy and safety of levetiracetam for outpatient alcohol detoxification.

    PubMed

    Müller, C A; Schäfer, M; Schneider, S; Heimann, H M; Hinzpeter, A; Volkmar, K; Förg, A; Heinz, A; Hein, J

    2010-07-01

    Anticonvulsant drugs are increasingly being used for alcohol detoxification in in- and outpatient settings. The aim of this study was to examine the efficacy, medical safety and mid-term outcome of levetiracetam, a drug with no marked liver toxicity, for outpatient alcohol detoxification. This was an open-label observational study. After screening eligibility for outpatient alcohol detoxification, patients were seen daily for 5 days and received levetiracetam in a flexible dosage regime between 500 and 4 000 mg/d for a maximum of 7 days. Diazepam was used as a rescue medication. The severity of alcohol withdrawal was evaluated daily using the ALCOHOL WITHDRAWAL SYNDROME SCALE (AWSS). Mid-term treatment outcome was assessed at a 6-month follow-up. A total number of 131 consecutively admitted alcohol-dependent patients received an outpatient detoxification treatment, 122 (93.1%) completed the programme successfully. The mean initial dose of levetiracetam was 1 850 mg/d. Alcohol withdrawal syndrome as indicated by the AWSS score decreased clearly over 5 days. Overall, the medication was well tolerated. There was no treatment discontinuations due to side effects of levetiracetam. No serious medical complications, especially seizures or deliria, were observed during the detoxification. At the 6-month follow-up, 57 patients (43.5%) were still abstinent. Patients with previous detoxifications had a significant higher risk for relapse (HR=1.88; p=0.016; CI 95%: 1.12-3.14) than patients without previous treatments. The findings of this study provide some evidence that levetiracetam is an efficacious and safe treatment option for outpatient alcohol detoxification. Further randomised, controlled trials including mid- and long-term follow-ups are needed to confirm these findings. Copyright Georg Thieme Verlag KG Stuttgart New York.

  11. Acute Alcohol Effects on Repetition Priming and Word Recognition Memory with Equivalent Memory Cues

    ERIC Educational Resources Information Center

    Ray, Suchismita; Bates, Marsha E.

    2006-01-01

    Acute alcohol intoxication effects on memory were examined using a recollection-based word recognition memory task and a repetition priming task of memory for the same information without explicit reference to the study context. Memory cues were equivalent across tasks; encoding was manipulated by varying the frequency of occurrence (FOC) of words…

  12. A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine Transmission as Assessed by [11 C]-(+)-PHNO.

    PubMed

    Thiruchselvam, Thulasi; Wilson, Alan A; Boileau, Isabelle; Le Foll, Bernard

    2017-06-01

    Previous positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D 2 /D 3 agonist radiotracer, [ 11 C]-(+)-propyl-hexahydro-naphtho-oxazin ([ 11 C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D 3 receptor also enables measuring changes in D 3 -rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [ 11 C]-(+)-PHNO binding in the striatum and in D 3 -rich extra-striatal areas. Eight healthy drinkers underwent 2 [ 11 C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [ 11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the 2 scans. Acute alcohol administration did not significantly reduce [ 11 C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15). Similarly, there were no changes in binding in the D 3 -rich areas of the ventral pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15). However, greater percent change in [ 11 C]-(+)-PHNO binding (ΔBP ND ) between scans was related to lower blood alcohol levels. Using the agonist radiotracer, [ 11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is not associated with robust changes in tracer binding in striatal or extra-striatal regions. However, we found that changes in [ 11 C]-(+)-PHNO binding following alcohol are dependent on blood alcohol levels suggesting that increases in DA may occur at lower stimulating doses. The effect of lower doses of alcohol on DA warrants further investigation in a

  13. delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.

    PubMed

    Wise, Laura E; Varvel, Stephen A; Selley, Dana E; Wiebelhaus, Jason M; Long, Kelly A; Middleton, Lisa S; Sim-Selley, Laura J; Lichtman, Aron H

    2011-10-01

    Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.

  14. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  15. S-adenosylmethionine decreases the peak blood alcohol levels 3 h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver.

    PubMed

    Bardag-Gorce, Fawzia; Oliva, Joan; Wong, Wesley; Fong, Stephanie; Li, Jun; French, Barbara A; French, Samuel W

    2010-12-01

    An alcohol bolus causes the blood alcohol level (BAL) to peak at 1-2 h post ingestion. The ethanol elimination rate is regulated by alcohol metabolizing enzymes, primarily alcohol dehydrogenase (ADH1), acetaldehyde dehydrogenase (ALDH), and cytochrome P450 (CYP2E1). Recently, S-adenosylmethionine (SAMe) was found to reduce acute BALs 3 h after an alcohol bolus. The question, then, was: what is the mechanism involved in this reduction of BAL by feeding SAMe? To answer this question, we investigated the changes in ethanol metabolizing enzymes and the epigenetic changes that regulate the expression of these enzymes during acute binge drinking and chronic drinking. Rats were fed a bolus of ethanol with or without SAMe, and were sacrificed at 3 h or 12 h after the bolus. RT-PCR and Western blot analyses showed that SAMe significantly induced ADH1 levels in the 3 h liver samples. However, SAMe did not affect the changes in ADH1 protein levels 12 h post bolus. Since SAMe is a methyl donor, it was postulated that the ADH1 gene expression up regulation at 3 h was due to a histone modification induced by methylation from methyl transferases. Dimethylated histone 3 lysine 4 (H3K4me2), a modification responsible for gene expression activation, was found to be significantly increased by SAMe at 3 h post bolus. These results correlated with the low BAL found at 3 h post bolus, and support the concept that SAMe increased the gene expression to increase the elimination rate of ethanol in binge drinking by increasing H3K4me2. Copyright © 2010 Elsevier Inc. All rights reserved.

  16. Abrupt opium discontinuation has no significant triggering effect on acute myocardial infarction.

    PubMed

    Masoomi, Mohammad; Zare, Jahangir; Nasri, Hamidreza; Mirzazadeh, Ali; Sheikhvatan, Mehrdad

    2011-04-01

    A deleterious effect of withdrawal symptoms due to abrupt discontinuation of opium on the cardiovascular system is one of the recent interesting topics in the cardiovascular field. The current study hypothesized that the withdrawal syndrome due to discontinuing opium might be an important trigger for the appearance of acute myocardial infarction. Eighty-one opium-addicted individuals who were candidates for cardiovascular clinical evaluation and consecutively hospitalized in the coronary care unit (CCU) ward of Shafa Hospital in Kerman between January and July 2009 were included in the study and categorized in the case group, including patients experiencing withdrawal symptoms within 6-12 h after the reduced or discontinued use of opium according to the Diagnostic and Statistical Manual of Mental Disorders-revised IV version (DSM-IV-R) criteria for opium dependence and withdrawal, and the control group, without opium withdrawal symptoms. The appearance of acute myocardial infarction was compared between the two groups using multivariable regression models. Acute myocardial infarction occurred in 50.0% of those with withdrawal symptoms and in 45.1% of patients without evidence of opium withdrawal (P = 0.669). Multivariable analysis showed that opium withdrawal symptoms were not a trigger for acute myocardial infarction adjusting for demographic characteristics, marital status, education level and common coronary artery disease risk profiles [odds ratio (OR) = 0.920, 95% confidence interval (CI) = 0.350-2.419, P = 0.866]. Also, daily dose of opium before reducing or discontinuing use did not predict the appearance of myocardial infarction in the presence of confounder variables (OR = 0.975, 95% CI = 0.832-1.143, P = 0.755). Withdrawal syndrome due to abrupt discontinuation of opium does not have a triggering role for appearance of acute myocardial infarction.

  17. Alcohol-preferring P rats emit spontaneous 22-28 kHz ultrasonic vocalizations that are altered by acute and chronic alcohol experience.

    PubMed

    Reno, James M; Thakore, Neha; Gonzales, Rueben; Schallert, Timothy; Bell, Richard L; Maddox, W Todd; Duvauchelle, Christine L

    2015-05-01

    Emotional states are often thought to drive excessive alcohol intake and influence the development of alcohol use disorders. To gain insight into affective properties associated with excessive alcohol intake, we utilized ultrasonic vocalization (USV) detection and analyses to characterize the emotional phenotype of selectively bred alcohol-preferring (P) rats; an established animal model of excessive alcohol intake. USVs emitted by rodents have been convincingly associated with positive (50-55 kHz frequency-modulated [FM]) and negative (22-28 kHz) affective states. Therefore, we hypothesized that 50-55 and 22-28 kHz USV emission patterns in P rats would reveal a unique emotional phenotype sensitive to alcohol experience. 50-55 kHz FM and 22-28 kHz USVs elicited from male P rats were assessed during access to water, 15 and 30% EtOH (v/v). Ethanol (EtOH; n = 12) or water only (Control; n = 4) across 8 weeks of daily drinking-in-the-dark (DID) sessions. Spontaneous 22-28 kHz USVs are emitted by alcohol-naïve P rats and are enhanced by alcohol experience. During DID sessions when alcohol was not available (e.g., "EtOH OFF" intervals), significantly more 22-28 kHz than 50-55 kHz USVs were elicited, while significantly more 50-55 kHz FM than 22-28 kHz USVs were emitted when alcohol was available (e.g., "EtOH ON" intervals). In addition, USV acoustic property analyses revealed chronic effects of alcohol experience on 22-28 kHz USV mean frequency, indicative of lasting alcohol-mediated alterations to neural substrates underlying emotional response. Our findings demonstrate that acute and chronic effects of alcohol exposure are reflected in changes in 22-28 and 50-55 kHz FM USV counts and acoustic patterns. These data support the notion that initiation and maintenance of alcohol intake in P rats may be due to a unique, alcohol-responsive emotional phenotype and further suggest that spontaneous 22-28 kHz USVs serve as behavioral markers for excessive

  18. Alcohol myopia and goal commitment

    PubMed Central

    Sevincer, A. Timur; Oettingen, Gabriele

    2014-01-01

    According to alcohol myopia theory, acute alcohol consumption leads people to disproportionally focus on the salient rather than the peripheral aspects of a situation. We summarize various studies exploring how myopic processes resulting from acute alcohol intake affect goal commitment. After consuming alcohol student participants felt strongly committed to an important personal goal even though they had low expectations of successfully attaining the goal. However, once intoxicated participants were sober again (i.e., not myopic anymore) they failed to act on their goal commitment. In line with alcohol myopia theory, strong goal commitment as a result of alcohol intake was mediated by intoxicated (vs. sober) participants disproportionally focusing on the desirability rather than the feasibility of their goal. Further supporting alcohol myopia theory, when the low feasibility of attaining a particular goal was experimentally made salient (either explicitly or implicitly by subliminal priming), intoxicated participants felt less committed than those who consumed a placebo. We discuss these effects of acute alcohol intake in the context of research on the effects of chronic alcohol consumption on goal commitment. PMID:24624106

  19. The effect of flavonol glycosides on opiate withdrawal.

    PubMed

    Capasso, Anna

    2007-07-01

    Our interest has been centered on flavonol glycosides from Croton Menthodorus (Euphorbiaceae) and Aristeguietia discolor (Asteraceae). In this respect, the effect of flavonol glycosides from Croton Menthodorus (Euphorbiaceae) and Aristeguietia discolor (Asteraceae) was investigated on the naloxone-precipitated withdrawal contracture of the acute morphine-dependent guinea-pig ileum in vitro. Furthermore, the effect of these flavonol glycosides was also considered on DAGO (highly selective micro-agonist) and U50-488H (highly selective k-agonist) withdrawal to test whether the possible interaction of flavonol glycosides on opioid withdrawal involves micro- and/or k-opioid receptors. Flavonol glycosides from Croton Menthodorus (1 x 10(-5), 5 x 10(-5) and 1 x 10(-4) M) and from Aristeguietia discolor (1 x 10(-7)-1 x 10(-6)-1 x 10(-5) M) before or after the opioid agonists were able to both prevent and reverse the naloxone-induced contracture after exposure to micro (morphine and DAGO) or k (U50-488H) opiate agonists in a concentration-dependent fashion. Both acetylcholine response and electrical stimulation were reduced by flavonol glycosides treatment as well as the final opiate withdrawal was still reduced. The results of the present study indicate that flavonol glycosides were able to produce significant influence on the opiate withdrawal in vitro and these compounds were able to exert their effects both at micro and k opioid agonists.

  20. Effects of acute alcohol consumption and vitamin E co-treatment on oxidative stress parameters in rats tongue.

    PubMed

    Carrard, V C; Pires, A S; Mendez, M; Mattos, F; Moreira, J C F; Sant'Ana Filho, M

    2009-06-01

    The aim of this study was to evaluate the effects of acute alcohol consumption and vitamin E co-treatment upon oxidative stress parameters in rats tongue. Thirty-eight, Wistar rats were separated into five groups (alcohol, alcohol/vitamin E, control, Tween, vitamin E). Alcohol and alcohol vitamin E groups had the standard diet, and 40% alcohol on drinking water. Other groups were fed with the same standard diet and water ad libitum. Vitamin E was given by gavage to vitamin E and alcohol/vitamin E rats twice a week. Alcohol and control groups were subjected to saline gavage and Tween group to 5% Tween 80 solution, the vitamin E vehicle. At day 14, the animals were anesthetized and specimens were obtained from tongue. Lipid peroxidation (TBARS), protein oxidative damage, catalase (CAT) and superoxide dismutase (SOD) activities were quantified. Alcohol group decreased TBARS in relation to control group and alcohol vitamin-treated animals decreased TBARS when compared to Tween and vitamin E groups. SOD activity was lower and CAT activity was higher in animals treated with both alcohol and vitamin E. These results suggest that short-term alcohol consumption decreases lipid peroxidation levels. Alternatively, alcohol/vitamin E group increased CAT, showing the toxicity of this association.

  1. Factor Analysis and Psychometric Properties of the Minnesota Nicotine Withdrawal Scale and the Minnesota Nicotine Withdrawal Scale-Revised: Italian Version.

    PubMed

    Svicher, Andrea; Beghè, Agnese; Mangiaracina, Giacomo; Cosci, Fiammetta

    2017-01-01

    We run Exploratory and Confirmatory Factor Analyses of the Minnesota Nicotine Withdrawal Scale (MNWS) and of the MNWS-Revised (MNWS-R). Psychometric properties were also explored. Adult Italian smokers, 366 in all, were assessed via the MNWS-R together with rating scales measuring cigarette dependence, alcohol use, anxiety sensitivity and negative affect at baseline and after 3 months. The MNWS showed good psychometric properties (α = 0.85; rtt = 0.59) and a unidimensional factor structure. The 2-factor model of MNWS-R had the best fit and the factors were labelled psychological symptoms (α = 0.86; rtt = 0.59) and associated somatic features (α = 0.64; rtt = 0.45). MNWS showed 1 factor; MNWS-R showed 2 relatively dependent factors. The results need to be replicated in smokers in withdrawal. © 2017 S. Karger AG, Basel.

  2. Effect of Withinia Somnifera and Shilajit on Alcohol Addiction in Mice

    PubMed Central

    Bansal, Priya; Banerjee, Sugato

    2016-01-01

    Background: Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti-addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. Objective: Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential. Materials and Methods: Effect of ashwagandha churna and shilajit was measured on ethanol withdrawal anxiety using elevated plus maze. Role of ashwagandha and shilajit on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herbs on corticohippocampal GABA, dopamine, and serotonin levels. Results: Both ashwagandha and shilajit were found to reduce alcohol withdrawal anxiety in a dose-dependent manner. These herbs alone or in combination also decreased ethanol intake and increased water intake significantly after 21 days of chronic administration. Chronic administration of ashwagandha was found to significantly increase GABA and serotonin levels whereas shilajit altered cortico-hippocampal dopamine in mice. Conclusion: These central nervous system active herbs alone or in combination reduced both alcohol dependence and withdrawal thus showing promising anti-addictive potential. SUMMARY Withinia Somnifera alone and in combination with Shilajeet prevented ethanol withdrawal and alcohol addiction Abbreviations used: GABA: Gama aminobutyric acid, CNS: Central Nervous System, CPP:Condition place preference, DA: Dopamine, 5-HT: 5-hydroxytryptamine, NMDA:N-methyl-D-aspartate PMID:27279696

  3. Effect of Withinia Somnifera and Shilajit on Alcohol Addiction in Mice.

    PubMed

    Bansal, Priya; Banerjee, Sugato

    2016-05-01

    Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti-addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential. Effect of ashwagandha churna and shilajit was measured on ethanol withdrawal anxiety using elevated plus maze. Role of ashwagandha and shilajit on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herbs on corticohippocampal GABA, dopamine, and serotonin levels. Both ashwagandha and shilajit were found to reduce alcohol withdrawal anxiety in a dose-dependent manner. These herbs alone or in combination also decreased ethanol intake and increased water intake significantly after 21 days of chronic administration. Chronic administration of ashwagandha was found to significantly increase GABA and serotonin levels whereas shilajit altered cortico-hippocampal dopamine in mice. These central nervous system active herbs alone or in combination reduced both alcohol dependence and withdrawal thus showing promising anti-addictive potential. Withinia Somnifera alone and in combination with Shilajeet prevented ethanol withdrawal and alcohol addiction Abbreviations used: GABA: Gama aminobutyric acid, CNS: Central Nervous System, CPP:Condition place preference, DA: Dopamine, 5-HT: 5-hydroxytryptamine, NMDA:N-methyl-D-aspartate.

  4. Ecological momentary assessment of acute alcohol use disorder symptoms: associations with mood, motives, and use on planned drinking days.

    PubMed

    Dvorak, Robert D; Pearson, Matthew R; Day, Anne M

    2014-08-01

    Several theories posit that alcohol is consumed both in relation to one's mood and in relation to different motives for drinking. However, there are mixed findings regarding the role of mood and motives in predicting drinking. Ecological momentary assessment (EMA) methods provide an opportunity to evaluate near real-time changes in mood and motives within individuals to predict alcohol use. In addition, endorsement of criteria of an alcohol use disorder (AUD) may also be sensitive to changes within subjects. The current study used EMA with 74 moderate drinkers who responded to fixed and random mood, motive, alcohol use, and AUD criteria prompts over a 21-day assessment period. A temporal pattern of daytime mood, evening drinking motivation, and nighttime alcohol use and acute AUD symptoms on planned drinking days was modeled to examine how these associations unfold throughout the day. The results suggest considerable heterogeneity in drinking motivation across drinking days. Additionally, an affect regulation model of drinking to cope with negative mood was observed. Specifically, on planned drinking days, the temporal association between daytime negative mood and the experience of acute AUD symptoms was mediated via coping motives and alcohol use. The current study found that motives are dynamic, and that changes in motives may predict differential drinking patterns across days. Further, the study provides evidence that emotion-regulation-driven alcohol involvement may need to be examined at the event level to fully capture the ebb and flow of negative affect motivated drinking.

  5. How acute and chronic alcohol consumption affects brain networks: insights from multimodal neuroimaging.

    PubMed

    Schulte, Tilman; Oberlin, Brandon G; Kareken, David A; Marinkovic, Ksenija; Müller-Oehring, Eva M; Meyerhoff, Dieter J; Tapert, Susan

    2012-12-01

    Multimodal imaging combining 2 or more techniques is becoming increasingly important because no single imaging approach has the capacity to elucidate all clinically relevant characteristics of a network. This review highlights recent advances in multimodal neuroimaging (i.e., combined use and interpretation of data collected through magnetic resonance imaging [MRI], functional MRI, diffusion tensor imaging, positron emission tomography, magnetoencephalography, MR perfusion, and MR spectroscopy methods) that leads to a more comprehensive understanding of how acute and chronic alcohol consumption affect neural networks underlying cognition, emotion, reward processing, and drinking behavior. Several innovative investigators have started utilizing multiple imaging approaches within the same individual to better understand how alcohol influences brain systems, both during intoxication and after years of chronic heavy use. Their findings can help identify mechanism-based therapeutic and pharmacological treatment options, and they may increase the efficacy and cost effectiveness of such treatments by predicting those at greatest risk for relapse. Copyright © 2012 by the Research Society on Alcoholism.

  6. Effect of 'chronic' versus 'acute' ketamine administration and its 'withdrawal' effect on behavioural alterations in mice: implications for experimental psychosis.

    PubMed

    Chatterjee, Manavi; Ganguly, Surajit; Srivastava, Mukesh; Palit, Gautam

    2011-01-01

    Lack of appropriate animal models simulating core behavioural aspects of human psychosis is a major limitation in schizophrenia research. The use of drugs, that is believed to act through N-methyl d-aspartate receptor, has been demonstrated to mimic relatively broader range of behavioural symptoms in putative animal models. Our goal in this study has been to further evaluate one such drug, ketamine in mice and characterize some selective behavioural phenotypes associated with the drug dosage, treatment period and withdrawal effects to extend the understanding of this model. Our results indicate that acute treatment of ketamine (100 mg/kg, i.p.) induced hyperlocomotory response and reduced the 'transfer-latency time' in passive avoidance test but did not have any effect in the forced swim test (negative symptoms). In contrast, chronic administration of ketamine not only produced significant 'hyperactivity' response but also enhanced the immobility period in animals during the forced swim test and reduced the latency period in the passive avoidance test. Further, these behavioural alterations persisted at least for 10 days after the withdrawal of ketamine treatment. These observations were substantiated by using standard typical and atypical antipsychotic drugs, haloperidol (0.25 mg/kg, i.p.), clozapine (10 mg/kg, i.p.) and risperidone (0.025 mg/kg, i.p.). Therefore, the present study suggests that the chronic treatment with ketamine has the potential of exhibiting changes in broader range of behavioural domains than the acute treatment. Hence, animals chronically treated with ketamine might serve as a useful tool to study the underlying pathogenic mechanisms associated with some symptoms in schizophrenia and other psychiatric disorders. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Withholding and withdrawing life-support therapy in an Emergency Department: prospective survey.

    PubMed

    Le Conte, Philippe; Baron, Denis; Trewick, David; Touzé, Marie Dominique; Longo, Céline; Vial, Irshaad; Yatim, Danielle; Potel, Gille

    2004-12-01

    Few studies have focused on decisions to withdraw or withhold life-support therapies in the emergency department. Our objectives were to identify clinical situations where life-support was withheld or withdrawn, the criteria used by physicians to justify their decisions, the modalities necessary to implement these decisions, patient disposition, and outcome. Prospective unicenter survey in an Emergency Department of a tertiary care teaching hospital. All non-trauma patients (n=119) for whom a decision to withhold or withdraw life-sustaining treatments was taken between January and September 1998. Choice of criteria justifying the decision to withhold or withdraw life-sustaining treatments, time interval from ED admission to the decision; type of decision implemented, outcome. Fourteen thousand eight hundred and seventy-five non-trauma patients were admitted during the study period, 119 were included, mean age 75+/-13 years. Resuscitation procedures were instituted for 96 (80%) patients before a subsequent decision was taken. Physicians chose on average 6+/-2 items to justify their decision; the principal acute medical disorder and futility of care were the two criteria most often used. Median time interval to reach the decision was 187 min. Withdrawal involved 37% of patients and withholding 63% of patients. The family was involved in the decision-making process in 72% of patients. The median time interval from the decision to death was 16 h (5 min to 140 days). Withdrawing and withholding life-support therapy involved elderly patients with underlying chronic cardiopulmonary disease or metastatic cancer or patients with acute non-treatable illness.

  8. Effects of Chronic Alcohol Exposure on the Modulation of Ischemia-Induced Glutamate Release via Cannabinoid Receptors in the Dorsal Hippocampus.

    PubMed

    Zheng, Lei; Wu, Xiaoda; Dong, Xiao; Ding, Xinli; Song, Cunfeng

    2015-10-01

    Chronic alcohol consumption is a critical contributing factor to ischemic stroke, as it enhances ischemia-induced glutamate release, leading to more severe excitotoxicity and brain damage. But the neural mechanisms underlying this phenomenon are poorly understood. We evaluated the effects of chronic alcohol exposure on the modulation of ischemia-induced glutamate release via CB1 and CB2 cannabinoid receptors during middle cerebral artery occlusion, using in vivo microdialysis coupled with high-performance liquid chromatography, in alcohol-naïve rats or rats after 1 or 30 days of withdrawal from chronic ethanol intake (6% v/v for 14 days). Intra-dorsal hippocampus (DH) infusions of ACEA or JWH133, selective CB1 or CB2 receptor agonists, respectively, decreased glutamate release in the DH in alcohol-naïve rats in a dose-dependent manner. Such an effect was reversed by co-infusions of SR141716A or AM630, selective CB1 or CB2 receptor antagonists, respectively. After 30 days, but not 1 day of withdrawal, ischemia induced an enhancement in glutamate release in the DH, as compared with non-alcohol-treated control group. Intra-DH infusions of JWH133, but not ACEA, inhibited ischemia-induced glutamate release in the DH after 30 days of withdrawal. Finally, 1 day of withdrawal did not alter the protein level of CB1 or CB2 receptors in the DH, as compared to non-alcohol-treated control rats. Whereas 30 days of withdrawal robustly decreased the protein level of CB1 receptors, but failed to alter the protein level of CB2 receptors, in the DH, as compared to non-alcohol-treated control rats. Together, these findings suggest that loss of expression/function of CB1 receptors, but not CB2 receptors in the DH, is correlated with the enhancement of ischemia-induced glutamate release after prolonged alcohol withdrawal. Copyright © 2015 by the Research Society on Alcoholism.

  9. Tobacco withdrawal symptoms mediate motivation to reinstate smoking during abstinence.

    PubMed

    Aguirre, Claudia G; Madrid, Jillian; Leventhal, Adam M

    2015-08-01

    Withdrawal-based theories of addiction hypothesize that motivation to reinstate drug use following acute abstinence is mediated by withdrawal symptoms. Experimental tests of this hypothesis in the tobacco literature are scant and may be subject to methodological limitations. This study utilized a robust within-subject laboratory experimental design to investigate the extent to which composite tobacco withdrawal symptomatology level and 3 unique withdrawal components (i.e., low positive affect, negative affect, and urge to smoke) mediated the effect of smoking abstinence on motivation to reinstate smoking. Smokers (≥10 cigarettes per day; N = 286) attended 2 counterbalanced sessions at which abstinence duration was differentially manipulated (1 hr vs. 17 hr). At both sessions, participants reported current withdrawal symptoms and subsequently completed a task in which they were monetarily rewarded proportional to the length of time they delayed initiating smoking, with shorter latency reflecting stronger motivation to reinstate smoking. Abstinence reduced latency to smoking initiation and positive affect and increased composite withdrawal symptom level, urge, and negative affect. Abstinence-induced reductions in latency to initiating smoking were mediated by each withdrawal component, with stronger effects operating through urge. Combined analyses suggested that urge, negative affect, and low positive affect operate through empirically unique mediational pathways. Secondary analyses suggested similar effects on smoking quantity, few differences among specific urge and affect subtypes, and that dependence amplifies some abstinence effects. This study provides the first experimental evidence that within-person variation in abstinence impacts motivation to reinstate drug use through withdrawal. Urge, negative affect, and low positive affect may reflect unique withdrawal-mediated mechanisms underlying tobacco addiction. (c) 2015 APA, all rights reserved).

  10. Protective Effects of Ethanolic Extracts from Artichoke, an Edible Herbal Medicine, against Acute Alcohol-Induced Liver Injury in Mice

    PubMed Central

    Tang, Xuchong; Wei, Ruofan; Deng, Aihua; Lei, Tingping

    2017-01-01

    Oxidative stress and inflammation are well-documented pathological factors in alcoholic liver disease (ALD). Artichoke (Cynara scolymus L.) is a healthy food and folk medicine with anti-oxidative and anti-inflammatory properties. This study aimed to evaluate the preventive effects of ethanolic extract from artichoke against acute alcohol-induced liver injury in mice. Male Institute of Cancer Research mice were treated with an ethanolic extract of artichoke (0.4, 0.8, and 1.6 g/kg body weight) by gavage once daily. Up to 40% alcohol (12 mL/kg body weight) was administered orally 1 h after artichoke treatment. All mice were fed for 10 consecutive days. Results showed that artichoke extract significantly prevented elevated levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol, and malondialdehyde. Meanwhile, the decreased levels of superoxide dismutase and glutathione were elevated by artichoke administration. Histopathological examination showed that artichoke attenuated degeneration, inflammatory infiltration and necrosis of hepatocytes. Immunohistochemical analysis revealed that expression levels of toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB) in liver tissues were significantly suppressed by artichoke treatment. Results obtained demonstrated that artichoke extract exhibited significant preventive protective effect against acute alcohol-induced liver injury. This finding is mainly attributed to its ability to attenuate oxidative stress and suppress the TLR4/NF-κB inflammatory pathway. To the best of our knowledge, the underlying mechanisms of artichoke on acute ALD have been rarely reported. PMID:28891983

  11. Protective Effects of Ethanolic Extracts from Artichoke, an Edible Herbal Medicine, against Acute Alcohol-Induced Liver Injury in Mice.

    PubMed

    Tang, Xuchong; Wei, Ruofan; Deng, Aihua; Lei, Tingping

    2017-09-11

    Oxidative stress and inflammation are well-documented pathological factors in alcoholic liver disease (ALD). Artichoke ( Cynara scolymus L.) is a healthy food and folk medicine with anti-oxidative and anti-inflammatory properties. This study aimed to evaluate the preventive effects of ethanolic extract from artichoke against acute alcohol-induced liver injury in mice. Male Institute of Cancer Research mice were treated with an ethanolic extract of artichoke (0.4, 0.8, and 1.6 g/kg body weight) by gavage once daily. Up to 40% alcohol (12 mL/kg body weight) was administered orally 1 h after artichoke treatment. All mice were fed for 10 consecutive days. Results showed that artichoke extract significantly prevented elevated levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol, and malondialdehyde. Meanwhile, the decreased levels of superoxide dismutase and glutathione were elevated by artichoke administration. Histopathological examination showed that artichoke attenuated degeneration, inflammatory infiltration and necrosis of hepatocytes. Immunohistochemical analysis revealed that expression levels of toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB) in liver tissues were significantly suppressed by artichoke treatment. Results obtained demonstrated that artichoke extract exhibited significant preventive protective effect against acute alcohol-induced liver injury. This finding is mainly attributed to its ability to attenuate oxidative stress and suppress the TLR4/NF-κB inflammatory pathway. To the best of our knowledge, the underlying mechanisms of artichoke on acute ALD have been rarely reported.

  12. Cocaine withdrawal

    MedlinePlus

    ... Substance use - cocaine withdrawal; Substance abuse - cocaine withdrawal; Drug abuse - cocaine withdrawal; Detox - cocaine ... Elsevier Saunders; 2016:chap 50. National Institute on Drug Abuse. What is cocaine? Updated May 2016. www.drugabuse. ...

  13. The effects of acute alcohol on psychomotor, set-shifting, and working memory performance in older men and women.

    PubMed

    Hoffman, Lauren A; Sklar, Alfredo L; Nixon, Sara Jo

    2015-05-01

    A limited number of publications have documented the effects of acute alcohol administration among older adults. Among these, only a few have investigated sex differences within this population. The current project examined the behavioral effects of acute low- and moderate-dose alcohol on 62 older (ages 55-70) male and female, healthy, light to moderate drinkers. Participants were randomly assigned to one of three dose conditions: placebo (peak breath alcohol concentration [BrAC] of 0 mg/dL), low (peak BrAC of 40 mg/dL), and moderate (peak BrAC of 65 mg/dL). Tasks assessed psychomotor, set-shifting, and working memory performance. Better set-shifting abilities were observed among women, whereas men demonstrated more efficient working memory, regardless of dose. The moderate-dose group did not significantly differ from the placebo group on any task. However, the low-dose group performed better than the moderate-dose group across measures of set shifting and working memory. Relative to the placebo group, the low-dose group exhibited better working memory, specifically for faces. Interestingly, there were no sex by dose interactions. These data suggest that, at least for our study's task demands, low and moderate doses of alcohol do not significantly hinder psychomotor, set-shifting, or working memory performance among older adults. In fact, low-dose alcohol may facilitate certain cognitive abilities. Furthermore, although sex differences in cognitive abilities were observed, these alcohol doses did not differentially affect men and women. Further investigation is necessary to better characterize the effects of sex and alcohol dose on cognition in older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

    PubMed

    Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

    2015-05-05

    Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Antioxidant and hepatoprotective effects of A. cerana honey against acute alcohol-induced liver damage in mice.

    PubMed

    Zhao, Haoan; Cheng, Ni; He, Liangliang; Peng, Guoxia; Xue, Xiaofeng; Wu, Liming; Cao, Wei

    2017-11-01

    A. cerana honey, gathered from Apis cerana Fabricius (A. cerana), has not been fully studied. Samples of honey originating from six geographical regions (mainly in the Qinling Mountains of China) were investigated to determine their antioxidant and hepatoprotective effects against acute alcohol-induced liver damage. The results showed that A. cerana honeys from the Qinling Mountains had high total phenolic contents (345.1-502.1mgGAkg -1 ), ascorbic acid contents (153.8-368.4mgkg -1 ), and strong antioxidant activities in DPPH radical scavenging activity assays (87.5-136.2IC50mgmL -1 ), ferric reducing antioxidant powers (191.8-317.4mgTroloxkg -1 ), and ferrous ion-chelating activities (27.5-35.5mgNa 2 EDTAkg -1 ). Pretreatment with A. cerana honey (Qinling Mountains) at 5, 10, or 20gkg -1 twice daily for 12weeks significantly inhibited serum lipoprotein oxidation and increased serum radical absorbance capacity (ORAC) (P<0.05). Moreover, A. cerana honey inhibited acute alcohol-induced increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum (P<0.05), reduced the production of hepatic malondialdehyde (MDA) (P<0.05), and promoted superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P<0.05). More importantly, it also remarkably inhibited the level of TGF-β1 in the serum and liver (P<0.05). The results of this study indicate that administration of A. cerana honey prevents acute alcohol-induced liver damage likely because of its antioxidant properties and ability to prevent oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

    PubMed

    Pinsky, C; Dua, A K; LaBella, F S

    1982-07-15

    Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

  17. Effects of alcohol on the membrane excitability and synaptic transmission of medium spiny neurons in the nucleus accumbens

    PubMed Central

    Marty, Vincent N.; Spigelman, Igor

    2013-01-01

    Chronic and excessive alcohol drinking lead to alcohol dependence and loss of control over alcohol consumption, with serious detrimental health consequences. Chronic alcohol exposure followed by protracted withdrawal causes profound alterations in the brain reward system that leads to marked changes in reinforcement mechanisms and motivational state. These long-lasting neuroadaptations are thought to contribute to the development of cravings and relapse. The nucleus accumbens (NAcc), a central component of the brain reward system, plays a critical role in alcohol-induced neuroadaptive changes underlying alcohol-seeking behaviors. Here we review the findings that chronic alcohol exposure produces long-lasting neuroadaptive changes in various ion channels that govern intrinsic membrane properties and neuronal excitability, as well as excitatory and inhibitory synaptic transmission in the NAcc that underlie alcohol-seeking behavior during protracted withdrawal. PMID:22445807

  18. Effects of the mGluR2/3 agonist LY379268 and the mGluR5 antagonist MPEP on handling-induced convulsions during ethanol withdrawal in mice

    PubMed Central

    Olive, M. Foster; Becker, Howard C.

    2008-01-01

    In alcoholic patients, ethanol is often consumed in a repeated cyclic pattern of intoxication followed by abstinence and the emergence of withdrawal symptoms. Repeated cycles of ethanol intoxication and withdrawal lead to a sensitization of CNS hyperexcitability as a result of an imbalance between inhibitory GABAergic transmission and excitatory glutamatergic transmission. Symptoms of alcohol withdrawal are usually treated pharmacologically with either benzodiazepines or anticonvulsant medications. However, recent evidence suggests that inhibition of glutamate transmission by stimulation of presynaptic inhibitory metabotropic glutamate receptors (i.e., mGluR2/3 receptors) or inhibition of mGluR5 receptors produces anticonvulsant effects. Therefore, the present study was designed to determine the effects the mGluR2/3 agonist LY379268 and the mGluR5 antagonist MPEP on ethanol withdrawal-induced seizure activity. Adult male C3H/He mice received chronic 16 h of ethanol vapor exposure in inhalation chambers followed by 8 hr of withdrawal daily for 4 consecutive days. During the final (fourth) withdrawal cycle, mice were evaluated hourly for handling-induced convulsions (HIC), and were treated with vehicle, LY379268 (0.3, 1 and 3 mg/kg) or MPEP (1, 3 and 10 mg/kg) treatment at 4 and 8 hr into withdrawal. Significant reductions in overall HIC activity were not observed following administration of either compound. These results suggest that inhibition of glutamate transmission by mGluR2/3 agonists or mGluR5 antagonists does not alter HIC activity during withdrawal from repeated ethanol exposure, and as such these compounds may have limited usefulness in the treatment of CNS hyperexcitability during alcohol withdrawal. PMID:18420113

  19. Anxiety and smoking cessation outcomes in alcohol-dependent smokers.

    PubMed

    Kelly, Megan M; Grant, Christoffer; Cooper, Sharon; Cooney, Judith L

    2013-02-01

    Anxiety-related characteristics, including anxiety sensitivity and trait anxiety, are elevated in individuals with alcohol and nicotine dependence and associated with greater difficulties with quitting smoking. However, little is known about how anxiety-related characteristics are related to smoking cessation outcomes in alcohol-dependent smokers. The present study, part of a larger smoking cessation clinical trial, examined associations between anxiety sensitivity, trait anxiety, nicotine withdrawal symptoms, smoking urges, and smoking cessation outcomes in a sample of 83 alcohol-dependent smokers. Participants were enrolled in concurrent alcohol and tobacco treatment as part of a substance-abuse intensive outpatient program. Smoking cessation treatment was administered in a 3-week cognitive-behavioral format that included 8 weeks of open-label nicotine patch treatment. Information on nicotine withdrawal, smoking urges, and CO-confirmed smoking consumption rates was collected at baseline, quit date, end of behavioral treatment, and at a 1-month follow-up. Higher levels of anxiety sensitivity were associated with more smoking urges due to anticipation of negative affect relief at quit date. Higher levels of trait anxiety were associated with more smoking urges due to positive reinforcement and anticipation of relief of negative affect at quit date, as well as more severe nicotine withdrawal symptoms at the end of treatment. Levels of anxiety sensitivity and trait anxiety were not associated with Cox regression survival times to relapse. These results indicate that for alcohol-dependent smokers, levels of anxiety sensitivity and trait anxiety are important to consider in the assessment and treatment of nicotine dependence.

  20. Intoxication- and withdrawal-dependent expression of central and peripheral cytokines following initial ethanol exposure

    PubMed Central

    Doremus-Fitzwater, Tamara L.; Buck, Hollin M.; Bordner, Kelly A.; Richey, Laura; Jones, Megan E.; Deak, Terrence

    2016-01-01

    Background Evidence has emerged demonstrating that ethanol influences cytokine expression within the CNS, although most studies have examined long-term exposure. Thus, the cytokine response to an acute ethanol challenge was investigated, in order to characterize profiles of cytokine changes following acute exposure. Methods Rats pups were injected intraperitoneally (i.p.) with 2-g/kg ethanol and IL-1 mRNA and protein assessed 0, 60, 120, 180, and 240 min post-injection (Exp. 1). In Exps. 2-5, the expression of several cytokines was examined in adult male rats during acute intoxication (3 hr after 4-g/kg ethanol), as well as withdrawal (18 hr post-injection), after i.p. and intragastric (i.g.) ethanol administration. Results Early in ontogeny, acute ethanol significantly decreased brain IL-1 mRNA and protein. Subsequently, when adult rats were examined, significant and temporally dynamic alterations in central and peripheral cytokines were observed following acute i.p. ethanol exposure (4-g/kg). Although cytokine- and region-dependent, central IL-6 expression was generally increased and TNFα decreased during intoxication, whereas IL-1 expression exhibited increases during withdrawal. In the periphery, acute i.p. ethanol elevated expression of all cytokines, with the response growing in magnitude as the time post-injection increased. Following acute i.g. ethanol (4-g/kg), intoxication-related increases in IL-6 expression were again observed in the PVN, although to a lesser extent. Long-term, voluntary, intermittent ethanol consumption resulted in tolerance to the effects of an i.g. ethanol challenge (4-g/kg) on PVN IL-6 expression, whereas these same elevations in IL-6 expression were still seen in the amygdala in rats with a history of moderate ethanol intake. Treatment with minocycline did not significantly attenuate i.p. or i.g. ethanol-induced changes in central cytokine expression. Conclusions Together, these studies provide a foundation for understanding

  1. [Physical diseases in alcoholism].

    PubMed

    Takase, Kojiro

    2015-09-01

    Rapid excessive alcohol drinking frequently causes disturbance of consciousness due to head trauma, brain edema, hypoglycemia, hyponatremia, hepatic coma and so on, provoked by acute alcohol intoxication. Rapid differential diagnosis and management are extremely important to save a life. On the other hands, the chronic users of alcohol so called alcoholism has many kinds of physical diseases such as liver diseases (i.e., fatty liver, alcoholic hepatitis, alcoholic liver cirrhosis and miscellaneous liver disease), diabetes mellitus, injury to happen in drunkenness, pancreas disease (i.e., acute and chronic pancreatitis and deterioration of chronic pancreatitis), gastrontestinal diseases (i.e., gastroduodenal ulcer), and so on. Enough attention should be paid to above mentioned diseases, otherwise they would turn worse more with continuation and increase in quantity of the alcohol. It should be born in its mind that the excessive drinking becomes the weapon threatening life.

  2. Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction.

    PubMed

    Rogers, Peter J; Heatherley, Susan V; Hayward, Robert C; Seers, Helen E; Hill, Joanne; Kane, Marian

    2005-06-01

    It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low. To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal. Participants were moderate to moderate-high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo. Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups. The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal

  3. Selective effects of acute alcohol intake on the prospective and retrospective components of a prospective-memory task with emotional targets.

    PubMed

    Walter, Nora T; Bayen, Ute J

    2016-01-01

    Prospective memory involves remembering to do something in the future and has a prospective component (remembering that something must be done) and a retrospective component (remembering what must be done and when it must be done). Initial studies reported an impairment in prospective-memory performance due to acute alcohol consumption. Retrospective-memory studies demonstrated that alcohol effects vary depending on the emotionality of the information that needs to be learned. The aim of the present study was to investigate possible differential effects of a mild acute alcohol dose (0.4 g/kg) on the prospective and retrospective components of prospective memory depending on cue valence. Seventy-five participants were allocated to an alcohol or placebo group and performed a prospective-memory task in which prospective-memory cue valence was manipulated (negative, neutral, positive). The multinomial model of event-based prospective memory (Smith and Bayen 2004) was used to measure alcohol and valence effects on the two prospective-memory components separately. Overall, no main effect of alcohol or valence on prospective-memory performance occurred. However, model-based analyses demonstrated a significantly higher retrospective component for positive compared with negative cues in the placebo group. In the alcohol group, the prospective component was weaker for negative than for neutral cues and the retrospective component was stronger for positive than for neutral cues. Group comparisons showed that the alcohol group had a significantly lower prospective component for negative cues and a lower retrospective component for neutral cues. This is the first study to demonstrate selective alcohol effects on prospective-memory components depending on prospective-memory cue valence.

  4. 78 FR 39256 - Polyvinyl Alcohol From Taiwan: Rescission of Antidumping Duty Administrative Review; 2012-2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... DEPARTMENT OF COMMERCE International Trade Administration [A-583-841] Polyvinyl Alcohol From...) is rescinding its administrative review of the antidumping duty order on polyvinyl alcohol (PVA) from... CCPC to the Department, ``Polyvinyl Alcohol from Taiwan: Withdrawal of Administrative Review Request...

  5. The Association Between Unhealthy Alcohol Use and Acute Care Expenditures in the 30 Days Following Hospital Discharge Among Older Veterans Affairs Patients with a Medical Condition.

    PubMed

    Chavez, Laura J; Liu, Chuan-Fen; Tefft, Nathan; Hebert, Paul L; Devine, Beth; Bradley, Katharine A

    2017-10-01

    Hospital readmissions and emergency department (ED) visits within 30 days of discharge are costly. Heavy alcohol use could predict increased risk for post-discharge acute care. This study assessed 30-day acute care utilization and expenditures for different categories of alcohol use. Veterans Affairs (VA) patients age ≥65 years with past-year alcohol screening, hospitalized for a medical condition, were included. VA and Medicare health care utilization data were used. Two-part models adjusted for patient demographics. Among 416,050 hospitalized patients, 25% had 30-day acute care use. Nondrinking patients (n = 267,746) had increased probability of acute care use, mean utilization days, and expenditures (difference of $345; 95% CI $268-$423), relative to low-risk drinkers (n = 105,023). High-risk drinking patients (n = 5,300) had increased probability of acute care use and mean utilization days, but not expenditures. Although these patients did not have greater acute care expenditures than low-risk drinking patients, they may nevertheless be vulnerable to poor post-discharge outcomes.

  6. [The morphometric characteristics of the main structural components of renal nephrons in the white rats with experimentally induced acute and chronic alcohol intoxication].

    PubMed

    Shcherbakova, V M

    2016-01-01

    The objective of the present work was to study the morphometric characteristics of the main structural components of renal nephrons in the white rats with the experimentally induced acute and chronic alcohol intoxication. We undertook the morphometric examination of the structural elements of rat kidneys with the subsequent statistical analysis of the data obtained. The results of the study give evidence of the toxic action of ethanol on all structural components of the nephron in the case of both acute and chronic alcohol intoxication. The study revealed some specific features of the development of pathological process in the renal tissue structures at different stages of alcohol intoxication. The most pronounced morphological changes were observed in the renal proximal tubules and the least pronounced ones in the structure of the renal glomeruli. The earliest morphological changes become apparent in distal convoluted tubules of the nephron; in the case of persistent alcoholemia, they first develop in the renal corpuscles and thereafter in the distal proximal tubules. The maximum changes occur in the case of acute alcohol intoxication and between 2 weeks and 2 months of chronic intoxication; they become less conspicuous during a later period.

  7. Withdrawal

    MedlinePlus

    ... However, withdrawal is considered a better method of contraception than none at all. Protection Against STDs Withdrawal ... 2013 More on this topic for: Teens Emergency Contraception Talking to Your Partner About Condoms Birth Control ...

  8. ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

    PubMed Central

    Yildirim, Emre; Connor, David A.; Gould, Thomas J.

    2015-01-01

    Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose–response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. PMID:25426579

  9. Acute Alcohol Intoxication and Suicide Among U.S. Ethnic/Racial Groups: Findings from the National Violent Death Reporting System

    PubMed Central

    Caetano, Raul; Kaplan, Mark S.; Huguet, Nathalie; McFarland, Bentson H.; Conner, Kenneth; Giesbrecht, Norman; Nolte, Kurt B.

    2012-01-01

    Background To assess the prevalence and sociodemographic correlates of suicide involving acute alcohol intoxication among U.S. ethnic minorities. Methods Data were derived from the restricted 2003–2009 National Violent Death Reporting System (NVDRS). The study focused on the sociodemographic and toxicological information of 59,384 male and female suicide decedents for 16 states of the U.S. Acute alcohol intoxication was defined as having a blood alcohol content (BAC) ≥ 0.08 g/dl. Overall, 76% of decedents were tested for the presence of alcohol. Results The proportion of suicide decedents with a positive BAC ranged from 47% among American Indians/Alaska Natives (AIs/ANs) to 23% among Asians/Pacific Islanders (PIs). Average BAC was highest among AIs/ANs. Among those who were tested for BAC, the proportion of decedents legally intoxicated prior to suicide was: Blacks, 15%; AIs/ANs, 36%; Asians/PIs, 13%; Hispanics, 28%. Bivariate associations showed that most suicide decedents who were legally intoxicated were male, younger than 30 years of age, with a high school education, not married, non-veterans, lived in metropolitan areas, and used a firearm to complete suicide. However, with the exception of Whites, most of these associations became not statistically significant in multivariate analysis. Conclusions Alcohol use and legal intoxication prior to completing suicide are common among U.S. ethnic groups, especially among males and those who are younger than 30 years of age. The AI/AN group had the highest mean BAC, the highest rate of legal intoxication and decedents who were particularly young. Suicide prevention strategies should address alcohol use as a risk factor. Alcohol problems prevention strategies should focus on suicide as a consequence of alcohol use, especially among AI/AN youth and young adults. PMID:23384174

  10. Refeeding syndrome is uncommon in alcoholics admitted to a hospital detoxification unit.

    PubMed

    Manning, S; Gilmour, M; Weatherall, M; Robinson, G M

    2014-05-01

    The refeeding syndrome is increasingly recognised. It is a serious change in electrolytes when nutrition is reintroduced to malnourished patients. Alcohol dependence is a risk factor for the refeeding syndrome. We report a prospective cohort study of 36 alcoholics hospitalised for withdrawal management. We found no evidence of refeeding syndrome in any patient after 3 days of hospitalisation, despite hypomagnesaemia, a risk factor for the refeeding syndrome being prevalent (44% of subjects). Low thiamine levels were infrequent affecting 3/29 (10%). We recommend that in alcoholics admitted for managed withdrawal, risk of refeeding syndrome appears to be low, and routine testing of repeat electrolytes appears unnecessary. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

  11. Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats

    PubMed Central

    Shnitko, Tatiana A.; Spear, Linda P.; Robinson, Donita L.

    2015-01-01

    Rationale Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. Objectives We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Methods Rats received intermittent intragastric ethanol, water or nothing during adolescence. In adulthood, electrically-evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Results Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50% in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. Conclusions The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats, and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age. PMID:26487039

  12. Acute Immunomodulatory Effects of Binge Alcohol Ingestion

    PubMed Central

    Afshar, Majid; Richards, Stephanie; Mann, Dean; Cross, Alan; Smith, Gordon B.; Netzer, Giora; Kovacs, Elizabeth; Hasday, Jeffrey

    2014-01-01

    BACKGROUND Blood alcohol is present in a third of trauma patients and has been associated with organ dysfunction. In both human studies and in animal models, it is clear that alcohol intoxication exerts immunomodulatory effects several hours to days after exposure, when blood alcohol is no longer detectable. The early immunomodulatory effects of alcohol while blood alcohol is still elevated are not well understood. METHODS Human volunteers achieved binge alcohol intoxication after high-dose alcohol consumption. Blood was collected for analysis prior to alcohol ingestion, and 20 min, 2 h, and 5 h after alcohol ingestion. Flow cytometry was performed on isolated peripheral blood mononuclear cells, and cytokine generation in whole blood was measured by enzyme-linked immunosorbent assay (ELISA) after 24-h stimulation with lipopolysaccharide (LPS) and phytohemagglutinin-M (PHA) stimulation. RESULTS An early pro-inflammatory state was evident at 20 min when blood alcohol levels were ~130 mg/dL, which was characterized by an increase in total circulating leukocytes, monocytes, and natural killer cells. During this time, a transient increase in LPS-induced tumor necrosis factor (TNF)-α levels and enhanced LPS sensitivity occurred. At 2 and 5 h post-alcohol binge, an anti-inflammatory state was shown with reduced numbers of circulating monocytes and natural killer cells, attenuated LPS-induced interleukin (IL)-1β levels, and a trend toward increased interleukin (IL)-10 levels. CONCLUSIONS A single episode of binge alcohol intoxication exerted effects on the immune system that caused an early and transient pro-inflammatory state followed by an anti-inflammatory state. PMID:25572859

  13. Prenatal and adult androgen activities in alcohol dependence.

    PubMed

    Lenz, B; Mühle, C; Braun, B; Weinland, C; Bouna-Pyrrou, P; Behrens, J; Kubis, S; Mikolaiczik, K; Muschler, M-R; Saigali, S; Sibach, M; Tanovska, P; Huber, S E; Hoppe, U; Eichler, A; Heinrich, H; Moll, G H; Engel, A; Goecke, T W; Beckmann, M W; Fasching, P A; Müller, C P; Kornhuber, J

    2017-07-01

    Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Acute alcohol consumption and secondary psychopathic traits increase ratings of the attractiveness and health of ethnic ingroup faces but not outgroup faces.

    PubMed

    Mitchell, Ian J; Gillespie, Steven M; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

    2015-01-01

    Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition.

  15. Cognitive and neurobiological mechanisms of alcohol-related aggression.

    PubMed

    Heinz, Adrienne J; Beck, Anne; Meyer-Lindenberg, Andreas; Sterzer, Philipp; Heinz, Andreas

    2011-06-02

    Alcohol-related violence is a serious and common social problem. Moreover, violent behaviour is much more common in alcohol-dependent individuals. Animal experiments and human studies have provided insights into the acute effect of alcohol on aggressive behaviour and into common factors underlying acute and chronic alcohol intake and aggression. These studies have shown that environmental factors, such as early-life stress, interact with genetic variations in serotonin-related genes that affect serotonergic and GABAergic neurotransmission. This leads to increased amygdala activity and impaired prefrontal function that, together, predispose to both increased alcohol intake and impulsive aggression. In addition, acute and chronic alcohol intake can further impair executive control and thereby facilitate aggressive behaviour.

  16. Acute effects of traditional Japanese alcohol beverages on blood glucose and polysomnography levels in healthy subjects

    PubMed Central

    Kido, Megumi; Asakawa, Akihiro; Koyama, Ken-Ichiro K.; Takaoka, Toshio; Tajima, Aya; Takaoka, Shigeru; Yoshizaki, Yumiko; Okutsu, Kayu; Takamine, Kazunori T.; Sameshima, Yoshihiro

    2016-01-01

    Background. Alcohol consumption is a lifestyle factor associated with type 2 diabetes. This relationship is reportedly different depending on the type of alcohol beverage. The purpose of this study was to examine the acute effects of traditional Japanese alcohol beverages on biochemical parameters, physical and emotional state, and sleep patterns. Methods. Six healthy subjects (three men and three women; age, 28.8 ± 9.5 years; body mass index, 21.4 ± 1.6 kg/m2) consumed three different types of alcohol beverages (beer, shochu, and sake, each with 40 g ethanol) or mineral water with dinner on different days in the hospital. Blood samples were collected before and 1, 2, and 12 h after drinking each beverage, and assessments of physical and emotional state were administered at the same time. In addition, sleep patterns and brain waves were examined using polysomnography. Results. Blood glucose levels at 1 h and the 12-h area under the curve (AUC) value after drinking shochu were significantly lower than that with water and beer. The 12-h blood insulin AUC value after drinking shochu was significantly lower than that with beer. Blood glucose × insulin level at 1 h and the 2-h blood glucose × insulin AUC value with shochu were significantly lower than that with beer. The insulinogenic indexes at 2 h with beer and sake, but not shochu, were significantly higher than that with water. The visual analogue scale scores of physical and emotional state showed that the tipsiness levels with beer, shochu, and sake at 1 h were significantly higher than that with water. These tipsiness levels were maintained at 2 h. The polysomnography showed that the rapid eye movement (REM) sleep latency with shochu and sake were shorter than that with water and beer. Conclusions. Acute consumption of alcohol beverages with a meal resulted in different responses in postprandial glucose and insulin levels as well as REM sleep latency. Alcohol beverage type should be taken into consideration

  17. Acute effects of traditional Japanese alcohol beverages on blood glucose and polysomnography levels in healthy subjects.

    PubMed

    Kido, Megumi; Asakawa, Akihiro; Koyama, Ken-Ichiro K; Takaoka, Toshio; Tajima, Aya; Takaoka, Shigeru; Yoshizaki, Yumiko; Okutsu, Kayu; Takamine, Kazunori T; Sameshima, Yoshihiro; Inui, Akio

    2016-01-01

    Background. Alcohol consumption is a lifestyle factor associated with type 2 diabetes. This relationship is reportedly different depending on the type of alcohol beverage. The purpose of this study was to examine the acute effects of traditional Japanese alcohol beverages on biochemical parameters, physical and emotional state, and sleep patterns. Methods. Six healthy subjects (three men and three women; age, 28.8 ± 9.5 years; body mass index, 21.4 ± 1.6 kg/m(2)) consumed three different types of alcohol beverages (beer, shochu, and sake, each with 40 g ethanol) or mineral water with dinner on different days in the hospital. Blood samples were collected before and 1, 2, and 12 h after drinking each beverage, and assessments of physical and emotional state were administered at the same time. In addition, sleep patterns and brain waves were examined using polysomnography. Results. Blood glucose levels at 1 h and the 12-h area under the curve (AUC) value after drinking shochu were significantly lower than that with water and beer. The 12-h blood insulin AUC value after drinking shochu was significantly lower than that with beer. Blood glucose × insulin level at 1 h and the 2-h blood glucose × insulin AUC value with shochu were significantly lower than that with beer. The insulinogenic indexes at 2 h with beer and sake, but not shochu, were significantly higher than that with water. The visual analogue scale scores of physical and emotional state showed that the tipsiness levels with beer, shochu, and sake at 1 h were significantly higher than that with water. These tipsiness levels were maintained at 2 h. The polysomnography showed that the rapid eye movement (REM) sleep latency with shochu and sake were shorter than that with water and beer. Conclusions. Acute consumption of alcohol beverages with a meal resulted in different responses in postprandial glucose and insulin levels as well as REM sleep latency. Alcohol beverage type should be taken into consideration

  18. Effects of acute combined serotonin and dopamine depletion on cue-induced drinking intention/desire and cognitive function in patients with alcohol dependence.

    PubMed

    Sun, Hong-Qiang; Liu, Yu; Li, Peng; Bao, Yan-Ping; Sheng, Li-Xia; Zhang, Rui-Ling; Cao, Yan-Jun; Di, Xiao-Lan; Yang, Fu-De; Wang, Fan; Luo, Yi-Xiao; Lu, Lin

    2012-08-01

    Alcohol cues can precipitate the desire to drink and cause relapse in recovering alcohol-dependent patients. Serotonin and dopamine may play a role in alcohol cue-induced craving. Acute combined tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe) depletion (CMD) in the diet attenuates the synthesis of serotonin and dopamine in the human brain. However, no study of the effects of acute CMD has been previously conducted. Therefore, we investigated whether the attenuation of serotonin and dopamine synthesis changes cue-induced alcohol craving in recently abstinent alcoholics. In this double-blind, randomized, placebo-controlled, crossover design, 12 male patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for alcohol dependence were divided into two conditions: (1) monoamine depletion (i.e., consumption of a concentrated amino acid beverage that resulted in a rapid and significant decrease in plasma-free Tyr/Phe/Trp) and (2) balanced condition (i.e., consumption of a similar beverage that contained Tyr/Phe/Trp). The participants were scheduled for two experimental sessions, with an interval of ≥7 days. The cue-induced craving test session was conducted 6h after each amino acid beverage administration. Drinking urge, blood pressure, heart rate, working memory, and attention/psychomotor performance were assessed before and after administration. Compared with the balanced condition, the monoamine depletion condition significantly increased drinking intention/desire and diastolic blood pressure. Cognitive performance was not different between the two conditions. Acute combined serotonin and dopamine depletion may increase drinking intention/desire and diastolic blood pressure without influencing cognitive function. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Chronic ethanol intake induces partial microglial activation that is not reversed by long-term ethanol withdrawal in the rat hippocampal formation.

    PubMed

    Cruz, Catarina; Meireles, Manuela; Silva, Susana M

    2017-05-01

    Neuroinflammation has been implicated in the pathogenesis of several disorders. Activation of microglia leads to the release of pro-inflammatory mediators and microglial-mediated neuroinflammation has been proposed as one of the alcohol-induced neuropathological mechanisms. The present study aimed to examine the effect of chronic ethanol exposure and long-term withdrawal on microglial activation and neuroinflammation in the hippocampal formation. Male rats were submitted to 6 months of ethanol treatment followed by a 2-month withdrawal period. Stereological methods were applied to estimate the total number of microglia and activated microglia detected by CD11b immunohistochemistry in the hippocampal formation. The expression levels of the pro-inflammatory cytokines TNF-α, COX-2 and IL-15 were measured by qRT-PCR. Alcohol consumption was associated with an increase in the total number of activated microglia but morphological assessment indicated that microglia did not exhibit a full activation phenotype. These data were supported by functional evidence since chronic alcohol consumption produced no changes in the expression of TNF-α or COX-2. The levels of IL-15 a cytokine whose expression is increased upon activation of both astrocytes and microglia, was induced by chronic alcohol treatment. Importantly, the partial activation of microglia induced by ethanol was not reversed by long-term withdrawal. This study suggests that chronic alcohol exposure induces a microglial phenotype consistent with partial activation without significant increase in classical cytokine markers of neuroinflammation in the hippocampal formation. Furthermore, long-term cessation of alcohol intake is not sufficient to alter the microglial partial activation phenotype induced by ethanol. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Youth social withdrawal behavior (hikikomori): A systematic review of qualitative and quantitative studies.

    PubMed

    Li, Tim M H; Wong, Paul W C

    2015-07-01

    Acute and/or severe social withdrawal behavior among youth was seen as a culture-bound psychiatric syndrome in Japan, but more youth social withdrawal cases in different countries have been discovered recently. However, due to the lack of a formal definition and diagnostic tool for youth social withdrawal, cross-cultural observational and intervention studies are limited. We aimed to consolidate existing knowledge in order to understand youth social withdrawal from diverse perspectives and suggest different interventions for different trajectories of youth social withdrawal. This review examined the current available scientific information on youth social withdrawal in the academic databases: ProQuest, ScienceDirect, Web of Science and PubMed. We included quantitative and qualitative studies of socially withdrawn youths published in English and academic peer-reviewed journals. We synthesized the information into the following categories: (1) definitions of youth social withdrawal, (2) developmental theories, (3) factors associated with youth social withdrawal and (4) interventions for socially withdrawn youths. Accordingly, there are diverse and controversial definitions for youth social withdrawal. Studies of youth social withdrawal are based on models that lead to quite different conclusions. Researchers with an attachment perspective view youth social withdrawal as a negative phenomenon, whereas those who adopt Erikson's developmental theory view it more positively as a process of seeking self-knowledge. Different interventions for socially withdrawn youths have been developed, mainly in Japan, but evidence-based practice is almost non-existent. We propose a theoretical framework that views youth social withdrawal as resulting from the interplay between psychological, social and behavioral factors. Future validation of the framework will help drive forward advances in theory and interventions for youth social withdrawal as an emerging issue in developed

  1. Phenomenology of gasoline intoxication and withdrawal symptoms among adolescents in India: a case series.

    PubMed

    Shah, R; Vankar, G K; Upadhyaya, H P

    1999-01-01

    Inhalant withdrawal symptoms have previously been described but not well documented. This case-series describes the sociodemographic and clinical characteristics of nine children and adolescents with gasoline abuse. Gasoline inhalation was the drug of choice in our patients. The mean age was 13.6 years and all the subjects belonged to low socioeconomic status. Most of the subjects used daily and all subjects reported alcohol abuse in the father. All subjects reported a syndrome of intoxication as described in previous reports. All subjects also reported a withdrawal syndrome including irritability, psychomotor retardation, anhedonia, dry mouth, sleep disturbances, craving, and increased lacrimation.

  2. Minimum Alcohol Prices and Outlet Densities in British Columbia, Canada: Estimated Impacts on Alcohol-Attributable Hospital Admissions

    PubMed Central

    Zhao, Jinhui; Martin, Gina; Macdonald, Scott; Vallance, Kate; Treno, Andrew; Ponicki, William; Tu, Andrew; Buxton, Jane

    2013-01-01

    Objectives. We investigated whether periodic increases in minimum alcohol prices were associated with reduced alcohol-attributable hospital admissions in British Columbia. Methods. The longitudinal panel study (2002–2009) incorporated minimum alcohol prices, density of alcohol outlets, and age- and gender-standardized rates of acute, chronic, and 100% alcohol-attributable admissions. We applied mixed-method regression models to data from 89 geographic areas of British Columbia across 32 time periods, adjusting for spatial and temporal autocorrelation, moving average effects, season, and a range of economic and social variables. Results. A 10% increase in the average minimum price of all alcoholic beverages was associated with an 8.95% decrease in acute alcohol-attributable admissions and a 9.22% reduction in chronic alcohol-attributable admissions 2 years later. A Can$ 0.10 increase in average minimum price would prevent 166 acute admissions in the 1st year and 275 chronic admissions 2 years later. We also estimated significant, though smaller, adverse impacts of increased private liquor store density on hospital admission rates for all types of alcohol-attributable admissions. Conclusions. Significant health benefits were observed when minimum alcohol prices in British Columbia were increased. By contrast, adverse health outcomes were associated with an expansion of private liquor stores. PMID:23597383

  3. Perception of sweet taste is important for voluntary alcohol consumption in mice.

    PubMed

    Blednov, Y A; Walker, D; Martinez, M; Levine, M; Damak, S; Margolskee, R F

    2008-02-01

    To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: alpha-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild-type mice, whereas Tas1r3 null mice were not different from wild type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion (CTA) to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in CTA to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol.

  4. PERCEPTION OF SWEET TASTE IS IMPORTANT FOR VOLUNTARY ALCOHOL CONSUMPTION IN MICE

    PubMed Central

    Blednov, Y.A.; Walker, D.; Martinez, M.; Levine, M.; Damak, S.; Margolskee, R.F.

    2012-01-01

    To directly evaluate the association between taste perception and alcohol intake, we used three different mutant mice, each lacking a gene expressed in taste buds and critical to taste transduction: α-gustducin (Gnat3), Tas1r3 or Trpm5. Null mutant mice lacking any of these three genes showed lower preference score for alcohol and consumed less alcohol in a two-bottle choice test, as compared with wild-type littermates. These null mice also showed lower preference score for saccharin solutions than did wild-type littermates. In contrast, avoidance of quinine solutions was less in Gnat3 or Trpm5 knockout mice than in wild type mice, whereas Tas1r3 null mice were not different from wild-type in their response to quinine solutions. There were no differences in null vs. wild-type mice in their consumption of sodium chloride solutions. To determine the cause for reduction of ethanol intake, we studied other ethanol-induced behaviors known to be related to alcohol consumption. There were no differences between null and wild-type mice in ethanol-induced loss of righting reflex, severity of acute ethanol withdrawal or conditioned place preference for ethanol. Weaker conditioned taste aversion to alcohol in null mice may have been caused by weaker rewarding value of the conditioned stimulus (saccharin). When saccharin was replaced by sodium chloride, no differences in conditioned taste aversion to alcohol between knockout and wild-type mice were seen. Thus, deletion of any one of three different genes involved in detection of sweet taste leads to a substantial reduction of alcohol intake without any changes in pharmacological actions of ethanol. PMID:17376151

  5. Caffeinated Alcohol Consumption Profiles and Associations with Use Severity and Outcome Expectancies

    PubMed Central

    Lau-Barraco, Cathy; Milletich, Robert J.; Linden, Ashley N.

    2014-01-01

    Growing evidence suggests that the consumption of caffeinated alcoholic beverages (CAB) may be riskier than alcohol alone. Efforts to identify patterns of CAB use and the correlates of such drinking patterns could further our conceptualization of and intervention for this health issue. Consequently, the current study aimed to (1) identify distinct classes of CAB users, (2) examine differences between classes on measures of alcohol and caffeine problems, and (3) compare distinct classes of CAB users on caffeine and alcohol outcome expectancies. Participants were 583 (31% men) undergraduate students from a psychology research pool. Latent profile analysis models were derived using four indicators: CAB use quantity, CAB use frequency, alcohol use quantity, and alcohol use frequency. Finding revealed four classes of drinkers: High Alcohol/High CAB (6.00%), High Alcohol/Moderate CAB (5.15%), High Alcohol/Low CAB (22.99%), and Low Alcohol/Low CAB (65.87%). The Low Alcohol/Low CAB class reported the lowest relative levels of caffeine dependence symptoms, caffeine withdrawal, alcohol use problems, and heavy episodic drinking frequency. Further, results indicated differential expectancy endorsement based on use profiles. CAB users in the High Alcohol/Low CAB class endorsed more positive alcohol expectancies than the Low Alcohol/Low CAB group. Those in the High Alcohol/High CAB class endorsed stronger withdrawal symptoms caffeine expectancies than all other classes. Inclusion of substance-specific expectancies into larger theoretical frameworks in future work of CAB use may be beneficial. Findings may inform intervention efforts for those at greatest risk related to CAB consumption. PMID:24210683

  6. Caffeinated alcohol consumption profiles and associations with use severity and outcome expectancies.

    PubMed

    Lau-Barraco, Cathy; Milletich, Robert J; Linden, Ashley N

    2014-01-01

    Growing evidence suggests that the consumption of caffeinated alcoholic beverages (CAB) may be riskier than alcohol alone. Efforts to identify patterns of CAB use and the correlates of such drinking patterns could further our conceptualization of and intervention for this health issue. Consequently, the current study aimed to (1) identify distinct classes of CAB users, (2) examine differences between classes on measures of alcohol and caffeine problems, and (3) compare distinct classes of CAB users on caffeine and alcohol outcome expectancies. Participants were 583 (31% men) undergraduate students from a psychology research pool. Latent profile analysis models were derived using four indicators: CAB use quantity, CAB use frequency, alcohol use quantity, and alcohol use frequency. Finding revealed four classes of drinkers: High Alcohol/High CAB (6.00%), High Alcohol/Moderate CAB (5.15%), High Alcohol/Low CAB (22.99%), and Low Alcohol/Low CAB (65.87%). The Low Alcohol/Low CAB class reported the lowest relative levels of caffeine dependence symptoms, caffeine withdrawal, alcohol use problems, and heavy episodic drinking frequency. Further, results indicated differential expectancy endorsement based on use profiles. CAB users in the High Alcohol/Low CAB class endorsed more positive alcohol expectancies than the Low Alcohol/Low CAB group. Those in the High Alcohol/High CAB class endorsed stronger withdrawal symptom caffeine expectancies than all other classes. Inclusion of substance-specific expectancies into larger theoretical frameworks in future work of CAB use may be beneficial. Findings may inform intervention efforts for those at greatest risk related to CAB consumption. © 2013.

  7. Alprazolam use and dependence. A retrospective analysis of 30 cases of withdrawal.

    PubMed Central

    Dickinson, B; Rush, P A; Radcliffe, A B

    1990-01-01

    From 1986 to 1989, the Chemical Dependency Recovery Program at Kaiser Permanente Hospital, Fontana, California, admitted an increasing number of patients for alprazolam dependence. Severe withdrawal reactions and adverse consequences with use were reported in the literature. In this review of 30 cases of alprazolam dependence and subsequent withdrawal, there was a statistically significant increase in the number of patient hospital days, the subjective symptoms, and staff time spent with patients compared with those in alcoholic controls. Most patients with diagnosed alprazolam dependence used doses in the range recommended by the package information at the time of admission. Patients with low preadmission doses of 1 mg or less per day showed notable withdrawal symptoms. The average duration of use was 29.9 months, considerably longer than suggested effective ranges. Most patients (28) had a chemical dependence history before being placed on alprazolam therapy; 24 had a positive family history of chemical dependence; and 24 had previous or current psychiatric care. PMID:2349800

  8. Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats.

    PubMed

    Mohan, L; Rao, U S C; Gopalakrishna, H N; Nair, V

    2011-01-01

    The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety.

  9. Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats

    PubMed Central

    Mohan, L.; Rao, U. S. C.; Gopalakrishna, H. N.; Nair, V.

    2011-01-01

    The present study investigates the anxiolytic activity of NR-ANX-C, a standardized polyherbal formulation containing the extracts of Withania somnifera, Ocimum sanctum, Camellia sinensis, Triphala, and Shilajit in ethanol withdrawal- (EW-) induced anxiety behavior in rats. Ethanol dependence in rats was produced by substitution of drinking water with 7.5% v/v alcohol for 10 days. Then, ethanol withdrawal was induced by replacing alcohol with drinking water, 12 hours prior to experimentation. After confirming induction of withdrawal symptoms in the alcohol deprived animals, the anxiolytic activity of the test compound in graded doses (10, 20, and 40 mg/kg) was compared to the standard drug alprazolam (0.08 mg/kg) in the elevated plus maze and bright and dark arena paradigms. In our study, single and repeated dose administration of NR-ANX-C reduced EW-induced anxiety in a dose-dependent manner. Even though the anxiolytic activity was not significant at lower doses, NR-ANX-C at the highest dose tested (40 mg/kg) produced significant anxiolytic activity that was comparable to the standard drug alprazolam. Based on our findings we believe that NR-ANX-C has the potential to be used as an alternative to benzodiazepines in the treatment of EW-induced anxiety. PMID:20953426

  10. Nicotine and Nicotine Abstinence Do Not Interfere with GABAA Receptor Neuroadaptations During Alcohol Abstinence.

    PubMed

    Hillmer, Ansel T; Kloczynski, Tracy; Sandiego, Christine M; Pittman, Brian; Anderson, Jon M; Labaree, David; Gao, Hong; Huang, Yiyun; Deluliis, Giuseppe; O'Malley, Stephanie S; Carson, Richard E; Cosgrove, Kelly P

    2016-04-01

    Alcohol dependence and tobacco smoking are highly comorbid, and treating both conditions simultaneously is controversial. Previously, we showed that tobacco smoking interferes with GABAA receptor neuroadaptations during alcohol withdrawal in humans, while this effect did not occur with continued nicotine use during alcohol abstinence in nonhuman primates. Here, we extend our previous work by measuring GABAA receptor availability with positron emission tomography (PET) during drug abstinence in nonhuman primates exposed to alcohol alone, nicotine and alcohol together, and alcohol abstinence with continued nicotine exposure. Twenty-four adolescent male rhesus macaques orally self-administered alcohol and nicotine, available separately in water and saccharin, over 20 weeks. The groups included alcohol alone (n = 8); nicotine and alcohol with simultaneous abstinence (n = 8); nicotine and alcohol with alcohol abstinence while nicotine was still available (n = 8); and a pilot group of animals consuming nicotine alone (n = 6). Animals were imaged with [(11)C]flumazenil PET to measure binding potential (BPND), an index of GABAA receptor availability. Imaging occurred at baseline (drug-naíve), and following alcohol and/or nicotine cessation at 1 day, 8 days, and 12 weeks of abstinence. Generalized linear mixed models were used to examine the time course of [(11)C]flumazenil BPND during alcohol abstinence across groups. Animals consumed 3.95 ± 1.22 g/kg/d alcohol and 55.4 ± 35.1 mg/kg/d nicotine. No significant group effects were observed in [(11)C]flumazenil BPND during alcohol abstinence; however, a main effect of time was detected. Post hoc analyses indicated that all groups abstaining from alcohol exhibited significantly increased GABAA receptor availability at 1 day and 8 days (but not 12 weeks) of abstinence relative to baseline, while no changes in [(11)C]flumazenil BPND during nicotine abstinence alone were observed. These data indicate that neither nicotine nor

  11. CHRONIC ALCOHOL NEUROADAPTATION AND STRESS CONTRIBUTE TO SUSCEPTIBILITY FOR ALCOHOL CRAVING AND RELAPSE

    PubMed Central

    BREESE, GEORGE R.; SINHA, RAJITA; HEILIG, MARKUS

    2010-01-01

    Alcoholism is a chronic relapsing disorder. Major characteristics observed in alcoholics during an initial period of alcohol abstinence are altered physiological functions and a negative emotional state. Evidence suggests that a persistent, cumulative adaptation involving a kindling/allostasis-like process occurs during the course of repeated chronic alcohol exposures that is critical for the negative symptoms observed during alcohol withdrawal. Basic studies have provided evidence for specific neurotransmitters within identified brain sites being responsible for the negative emotion induced by the persistent cumulative adaptation following intermittent-alcohol exposures. After an extended period of abstinence, the cumulative alcohol adaptation increases susceptibility to stress- and alcohol cue-induced negative symptoms and alcohol seeking, both of which can facilitate excessive ingestion of alcohol. In the alcoholic, stressful imagery and alcohol cues alter physiological responses, enhance negative emotion, and induce craving. Brain fMRI imaging following stress and alcohol cues has documented neural changes in specific brain regions of alcoholics not observed in social drinkers. Such altered activity in brain of abstinent alcoholics to stress and alcohol cues is consistent with a continuing ethanol adaptation being responsible. Therapies in alcoholics found to block responses to stress and alcohol cues would presumably be potential treatments by which susceptibility for continued alcohol abuse can be reduced. By continuing to define the neurobiological basis of the sustained alcohol adaptation critical for the increased susceptibility of alcoholics to stress and alcohol cues that facilitate craving, a new era is expected to evolve in which the high rate of relapse in alcoholism is minimized. 250 PMID:20951730

  12. An Update on CRF Mechanisms Underlying Alcohol Use Disorders and Dependence

    PubMed Central

    Quadros, Isabel Marian Hartmann; Macedo, Giovana Camila; Domingues, Liz Paola; Favoretto, Cristiane Aparecida

    2016-01-01

    Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic–pituitary–adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides. PMID:27818644

  13. Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

    PubMed

    Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

    2013-06-01

    In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

  14. Acute Alcohol Consumption and Secondary Psychopathic Traits Increase Ratings of the Attractiveness and Health of Ethnic Ingroup Faces but Not Outgroup Faces

    PubMed Central

    Mitchell, Ian J.; Gillespie, Steven M.; Leverton, Monica; Llewellyn, Victoria; Neale, Emily; Stevenson, Isobel

    2015-01-01

    Studies have consistently shown that both consumption of acute amounts of alcohol and elevated antisocial psychopathic traits are associated with an impaired ability for prepotent response inhibition. This may manifest as a reduced ability to inhibit prepotent race biased responses. Here, we tested the effects of acute alcohol consumption, and elevated antisocial psychopathic traits, on judgments of the attractiveness and health of ethnic ingroup and outgroup faces. In the first study, we show that following acute alcohol consumption, at a dose that is sufficient to result in impaired performance on tests of executive function, Caucasian participants judged White faces to be more attractive and healthier compared to when sober. However, this effect did not extend to Black faces. A similar effect was found in a second study involving sober Caucasian participants where secondary psychopathic traits were related to an intergroup bias in the ratings of attractiveness for White versus Black faces. These results are discussed in terms of a model which postulates that poor prefrontal functioning leads to increases in ingroup liking as a result of impaired abilities for prepotent response inhibition. PMID:25745403

  15. Universal screening for alcohol misuse in acute medical admissions is feasible and identifies patients at high risk of liver disease.

    PubMed

    Westwood, Greta; Meredith, Paul; Atkins, Susan; Greengross, Peter; Schmidt, Paul E; Aspinall, Richard J

    2017-09-01

    Many people who die from alcohol related liver disease (ARLD) have a history of recurrent admissions to hospital, representing potential missed opportunities for intervention. Universal screening for alcohol misuse has been advocated but it is not known if this is achievable or effective at detecting individuals at high risk of ARLD. We systematically screened all admissions to the Acute Medical Unit (AMU) of a large acute hospital using an electronic data capture system in real time. Patients at an increasing risk of alcohol harm were referred for either brief intervention (BI) or further assessment by an Alcohol Specialist Nursing Service (ASNS). Additional data were recorded on admission diagnoses, alcohol unit consumption, previous attendances, previous admissions, length of stay and mortality. Between July 2011 and March 2014, there were 53,165 admissions and 48,211 (90.68%) completed screening. Of these, 1,122 (2.3%) were classified as "increasing", and 1,921 (4.0%) as "high" risk of alcohol harm. High risk patients had more hospital admissions in the three previous years (average 4.74) than the low (3.00) and increasing (2.92) risk groups (p<0.001). The high risk patients also had more frequent emergency department (ED) attendances (7.68) than the lower (2.64) and increasing (3.81) groups (p<0.001 for both). A total of 1,396 (72.6%) of the high risk group were seen by the ASNS and 1,135 (81.2%) had an Alcohol Use Disorders Identification Test (AUDIT) score over 20 with 527 (37.8%) recording the maximum value of 40. Compared to the other groups, high risk patients had a distinct profile of admissions with the most common diagnoses being mental health disorders, gastro-intestinal bleeding, poisoning and liver disease. Universal screening of admissions for alcohol misuse is feasible and identifies a cohort with frequent ED attendances, recurrent admissions and an elevated risk of ARLD. An additional group of patients at an increasing risk of alcohol harm can be

  16. Grand Rounds: Alcoholic Hepatitis.

    PubMed

    Singal, Ashwani K; Louvet, Alexandre; Shah, Vijay H; Kamath, Patrick S

    2018-06-13

    A 33-year-old Caucasian male was admitted to hospital with recent onset of jaundice of 2-3 weeks duration. He reported heavy use of alcohol for the last 10 years with the last drink a day prior to the onset of symptoms. At admission, he was alert and oriented to time, place, and person, and was deeply jaundiced. His laboratory profile can be summarised as follows: haemoglobin 12.1 g/dl, white blood cell count 18,700 with 81% neutrophils, serum bilirubin 33 (direct 22) mg/dl, aspartate aminotransferase 147 IU/L, alanine aminotransferase 62 IU/L, alkaline phosphatase 117 IU/L, serum albumin 2.8 gm/dl, serum creatinine 0.6 mg/dl, prothrombin time 18.3 (control 14.5) seconds, and international normalized ratio 1.48. He was diagnosed with severe alcoholic hepatitis (Maddrey discriminant function score of 50) and treated with prednisolone for 28 days with symptomatic and biochemical improvement. His Lille score at seven days was 0.4, and his serum bilirubin had decreased to 3.5 mg/dl at the end of treatment. He was also seen by the addiction team during hospitalisation; he agreed to follow through on recommendations. He was dismissed after completing a three-week inpatient rehabilitation programme but relapsed to alcohol use three months later, and was readmitted with alcohol withdrawal. He was readmitted two months later (about six months from the first episode) for a second episode of severe alcoholic hepatitis. At admission, his model for end-stage liver disease score was 32 and he was treated again with corticosteroids. His Lille score at seven days was 0.6 and steroids were discontinued. The hospital course was complicated by spontaneous bacterial peritonitis and pneumonia with development of acute kidney injury. He continued to worsen, developing multiorgan failure. After a course of one month, the family's preference was for him to receive comfort measures. This scenario raises several questions. Copyright © 2018 European Association for the

  17. Linkage analyses of cannabis dependence, craving, and withdrawal in the San Francisco family study.

    PubMed

    Ehlers, Cindy L; Gizer, Ian R; Vieten, Cassandra; Wilhelmsen, Kirk C

    2010-04-05

    Cannabis is the most widely used illicit drug in the United States. There is ample evidence that cannabis use has a heritable component, yet the genes underlying cannabis use disorders are yet to be completely identified. This study's aims were to map susceptibility loci for cannabis use and dependence and two narrower cannabis-related phenotypes of "craving" and "withdrawal" using a family study design. Participants were 2,524 adults participating in the University of California San Francisco (UCSF) Family Alcoholism Study. DSM-IV diagnoses of cannabis dependence, as well as indices of cannabis craving and withdrawal, were obtained using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Genotypes were determined for a panel of 791 microsatellite polymorphisms. Multipoint variance component LOD scores were obtained using SOLAR. Genome-wide significance for linkage (LOD > 3.0) was not found for the DSM-IV cannabis dependence diagnosis; however, linkage analyses of cannabis "craving" and the cannabis withdrawal symptom of "nervous, tense, restless, or irritable" revealed five sites with LOD scores over 3.0 on chromosomes 1, 3, 6, 7, and 9. These results identify new regions of the genome associated with cannabis use phenotypes as well as corroborate the importance of several chromosome regions highlighted in previous linkage analyses for other substance dependence phenotypes.

  18. A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients.

    PubMed

    Croissant, Bernhard; Diehl, Alexander; Klein, Oliver; Zambrano, Sergio; Nakovics, Helmut; Heinz, Andreas; Mann, Karl

    2006-04-01

    This pilot study has been designed to collect preliminary data on the use of a new antiepileptic drug in the management of alcoholic patients. Oxcarbazepine (OXC) blocks voltage-sensitive sodium channels. Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons, thus reducing glutamatergic transmission at corticostriatal synapses. This reduction is of interest in the treatment of alcohol dependence, as acamprosate (ACP) modulates NMDA receptors, resulting in an inhibition of glutamatergic transmission. Furthermore, OXC has revealed a mood-stabilizing effect in bipolar affective disorders. We have compared OXC with ACP in relapse prevention in recently withdrawn alcohol-dependent patients. We investigated the efficacy and safety of OXC (vs ACP) by conducting a 24-week randomized, parallel-group, open-label, clinical trial on 30 acutely detoxified alcoholic patients. Survival analyses (Kaplan-Meier) were performed to look for evidence of a longer "survival" of patients receiving OXC. We assessed time to first severe relapse and additional secondary endpoints. After withdrawal, time to severe relapse and time to first consumption of any ethanol by OXC patients were not longer than for ACP patients. Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale-German version (OCDS-G) than relapsed patients. No undesired effects occurred when OXC patients consumed alcohol. Our findings indicate that it could be worthwhile to test relapse prevention using OXC in an adequate sample. While the current sample size clearly limits further conclusions from this pilot study, it is noteworthy that OXC is well tolerated, even when alcohol is on board. Thus, in medication-based relapse prevention, OXC could be a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or those who have affective liability. OXC certainly merits a larger placebo-controlled trial.

  19. Marijuana withdrawal and aggression among a representative sample of U.S. marijuana users

    PubMed Central

    Smith, Philip H.; Homish, Gregory G.; Leonard, Kenneth E.; Collins, R. Lorraine

    2013-01-01

    Background Previous laboratory-based research suggests that withdrawal from marijuana may cause increased aggression. It is unclear whether this finding extends beyond the laboratory setting to the general population of marijuana users. The purpose of this study was to test a cross-sectional association between marijuana withdrawal symptoms and aggression among a representative sample of U.S. adult marijuana users, and to test whether this association was moderated by previous history of aggression. Methods Data were analyzed from the National Epidemiologic Survey on Alcohol and Related Conditions. Wave Two data (2004–2005) were used for all variables except for history of aggression, which was assessed during the Wave One interview (2001–2002). Two outcomes were examined: self-report general aggression and relationship aggression. Odds ratios for aggression based on withdrawal symptoms and the interaction between withdrawal symptoms and history of aggression were calculated using logistic regression, adjusting for covariates and accounting for the complex survey design. Results Among marijuana users with a history of aggression, marijuana withdrawal was associated with approximately 60% higher odds of past year relationship aggression (p < 0.05). There was no association between withdrawal symptoms and relationship aggression among those without a history of aggression, and no association with general aggression regardless of history of aggression. Conclusions The findings from this study support the notion that laboratory-based increases in aggression due to marijuana withdrawal extend to the general population of marijuana users who have a previous history of aggression. PMID:23380439

  20. Suicidal Behavior and Alcohol Abuse

    PubMed Central

    Pompili, Maurizio; Serafini, Gianluca; Innamorati, Marco; Dominici, Giovanni; Ferracuti, Stefano; Kotzalidis, Giorgio D.; Serra, Giulia; Girardi, Paolo; Janiri, Luigi; Tatarelli, Roberto; Sher, Leo; Lester, David

    2010-01-01

    Suicide is an escalating public health problem, and alcohol use has consistently been implicated in the precipitation of suicidal behavior. Alcohol abuse may lead to suicidality through disinhibition, impulsiveness and impaired judgment, but it may also be used as a means to ease the distress associated with committing an act of suicide. We reviewed evidence of the relationship between alcohol use and suicide through a search of MedLine and PsychInfo electronic databases. Multiple genetically-related intermediate phenotypes might influence the relationship between alcohol and suicide. Psychiatric disorders, including psychosis, mood disorders and anxiety disorders, as well as susceptibility to stress, might increase the risk of suicidal behavior, but may also have reciprocal influences with alcohol drinking patterns. Increased suicide risk may be heralded by social withdrawal, breakdown of social bonds, and social marginalization, which are common outcomes of untreated alcohol abuse and dependence. People with alcohol dependence or depression should be screened for other psychiatric symptoms and for suicidality. Programs for suicide prevention must take into account drinking habits and should reinforce healthy behavioral patterns. PMID:20617037

  1. Acute effects of alcohol on inhibitory control and simulated driving in DUI offenders.

    PubMed

    Van Dyke, Nicholas; Fillmore, Mark T

    2014-06-01

    The public health costs associated with alcohol-related traffic accidents have prompted considerable research aimed at identifying characteristics of individuals who drive under the influence (DUI) in order to improve treatment and prevention strategies. Survey studies consistently show that DUI offenders self-report higher levels of impulsivity compared to their nonoffending counterparts. However, little is known about how individuals with a DUI history respond under alcohol. Inhibitory control is a behavioral component of impulsivity thought to underlie risky drinking and driving behaviors. The present study examined the degree to which DUI drivers display deficits of inhibitory control in response to alcohol and the degree to which alcohol impaired their simulated driving performance. It was hypothesized that DUI offenders would display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance. Young adult drivers with a history of DUI and a demographically-comparable group of drivers with no history of DUI (controls) were tested following a 0.65 g/kg dose of alcohol and a placebo. Inhibitory control was measured by using a cued go/no-go task. Drivers then completed a driving simulation task that yielded multiple indicators of driving performance, such as within-lane deviation, steering rate, centerline crossings and road edge excursions, and drive speed. Results showed that although DUI offenders self-reported greater levels of impulsivity than did controls, no group differences were observed in the degree to which alcohol impaired inhibitory control and driving performance. The findings point to the need to identify other aspects of behavioral dysfunction underlying the self-reported impulsivity among DUI offenders, and to better understand the specific driving situations that might pose greater risk to DUI offenders. The systematic study of candidate cognitive deficits in DUI offenders will provide important

  2. Cannabis Withdrawal, Posttreatment Abstinence, and Days to First Cannabis Use Among Emerging Adults in Substance Use Treatment: A Prospective Study

    PubMed Central

    Davis, Jordan P.; Smith, Douglas C.; Morphew, Jason W.; Lei, Xinrong; Zhang, Saijun

    2015-01-01

    Very little prospective research investigates how cannabis withdrawal is associated with treatment outcomes, and this work has not used the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) thresholds for cannabis withdrawal. The sample included 110 emerging adults entering outpatient substance use treatment who were heavy cannabis users with no other drug use and limited alcohol use. We used survival analyses to predict days to first use of cannabis and logistic regression to predict whether participants were abstinent and living in the community at 3 months. Those meeting criteria for cannabis withdrawal were more likely to return to use sooner than those not meeting criteria for cannabis withdrawal. However, the presence of cannabis withdrawal was not a significant predictor of 3-month abstinence. Emerging adults with DSM-5 cannabis withdrawal may have difficulty initiating abstinence in the days following their intake assessment, implying the need for strategies to mitigate their more rapid return to cannabis use. PMID:26877548

  3. Observing nurses has improved my alcohol dependency care.

    PubMed

    Jaques, Ellise

    2016-09-21

    My first placement in my first year of nursing training was on a gastrointestinal/hepatology ward. Alongside my mentor, I was caring for a patient who had been withdrawing from alcohol since admission to hospital the previous evening.

  4. Role of the satiety factor oleoylethanolamide in alcoholism.

    PubMed

    Bilbao, Ainhoa; Serrano, Antonia; Cippitelli, Andrea; Pavón, Francisco J; Giuffrida, Andrea; Suárez, Juan; García-Marchena, Nuria; Baixeras, Elena; Gómez de Heras, Raquel; Orio, Laura; Alén, Francisco; Ciccocioppo, Roberto; Cravatt, Benjamin F; Parsons, Loren H; Piomelli, Daniele; Rodríguez de Fonseca, Fernando

    2016-07-01

    Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show that alcohol administration causes the release of OEA in rodents, which in turn reduces alcohol consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears to rely on peripheral signaling mechanisms as alcohol self-administration is unaltered by intracerebral PPAR-α agonist administration, and the lesion of sensory afferent fibers (by capsaicin) abrogates the effect of systemically administered OEA on alcohol intake. Additionally, OEA is shown to block cue-induced reinstatement of alcohol-seeking behavior (an animal model of relapse) and reduce the severity of somatic withdrawal symptoms in alcohol-dependent animals. Collectively, these findings demonstrate a homeostatic role for OEA signaling in the behavioral effects of alcohol exposure and highlight OEA as a novel therapeutic target for alcohol use disorders and alcoholism. © 2015 Society for the Study of Addiction.

  5. Screening for hazardous drinking using the Michigan Alcohol Screening Test-Geriatric Version (MAST-G) in elderly persons with acute cerebrovascular accidents.

    PubMed

    Johnson-Greene, Doug; McCaul, Mary E; Roger, Patricia

    2009-09-01

    Effective and valid screening methods are needed to identify hazardous drinking in elderly persons with new onset acute medical illness. The goal of the current study was to examine the effectiveness of the Michigan Alcohol Screening Test-Geriatric Version (MAST-G) in identifying hazardous drinking among elderly patients with acute cerebrovascular accidents (CVA) and to compare the effectiveness of 2 shorter versions of the MAST-G with the full instrument. The study sample included 100 men and women who averaged 12 days posthemorrhagic or ischemic CVA admitted to a rehabilitation unit and who were at least 50 years of age and free of substance use other than alcohol. This cross-sectional validation study compared the 24-item full MAST-G, the 10-item Short MAST-G (SMAST-G), and a 2-item regression analysis derived Mini MAST-G (MMAST-G) to the reference standard of hazardous drinking during the past 3 months. Alcohol use was collected using the Timeline Followback (TLFB). Recent and lifetime alcohol-related consequences were collected using the Short Inventory of Problems (SIP). Nearly one-third (28%) of the study sample met the World Health Organization (WHO) criteria for hazardous drinking. Moderately strong associations were found for the MAST-G, SMAST-G, and MMAST-G with alcohol quantity and frequency and recent and lifetime alcohol consequences. All 3 MAST-G versions could differentiate hazardous from nonhazardous drinkers and had nearly identical area under the curve characteristics. Comparable sensitivity was found across the 3 MAST-G measures. The optimal screening threshold for hazardous drinking was 5 for the MAST-G, 2 for the SMAST-G, and 1 for the MMAST-G. The 10-item SMAST-G and 2-item MMAST-G are brief screening tests that show comparable effectiveness in detecting hazardous drinking in elderly patients with acute CVA compared with the full 24-item MAST-G. Implications for research and clinical practice are discussed.

  6. The sap of Acer okamotoanum decreases serum alcohol levels after acute ethanol ingestion in rats.

    PubMed

    Yoo, Yeong-Min; Jung, Eui-Man; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

    2011-10-01

    In the present study, we examined whether Acer okamotoanum (A. okamotoanum) sap decreased the serum alcohol and acetaldehyde levels after acute ethanol treatment in a rat model. Male rats were orally administered 25, 50 or 100% A. okamotoanum sap 30 min prior to oral challenge with 3 ml of ethanol (15 ml/kg of a 20% ethanol solution in water), and the blood concentrations of alcohol and acetaldehyde were analyzed up to 7 h after the treatment. Pre-treatment with the sap significantly decreased the blood ethanol and acetaldehyde concentrations after 5 h when compared with ethanol treatment alone (a negative control). The expression levels of liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) mRNA were increased significantly in animals pre-treated with A. okamotoanum sap when compared with negative and positive controls. The data suggest that sap pre-treatment enhanced the alcohol metabolism rate in the rat liver. To investigate the involvement of mitochondrial regulation in the ethanol-induced hepatocyte apoptosis, we carried out an immunohistochemical analysis of Bax and Bcl-2. Pre-treatment with sap significantly decreased Bax expression and increased Bcl-2 expression 7 h after ethanol administration when compared with the negative control. The data suggest that A. okamotoanum sap pre-treatment may reduce the alcohol-induced oxidative stress in the rat liver.

  7. Pharmacotherapeutic Treatment of Alcohol Dependence: An Overview

    ERIC Educational Resources Information Center

    Graves, Erin; Goodwin, Lloyd R., Jr.

    2008-01-01

    Pharmacotherapy medications can reduce the likelihood of relapse, decrease craving intensity and severity of withdrawal symptoms, and bolster the likelihood of achieving and maintaining recovery goals for many individuals seeking recovery from alcohol dependence. An overview of the benefits and concerns of integrating pharmacotherapeutic…

  8. Acute alcohol administration improves skilled reaching success in intact but not 6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and anxiolytic effects of alcohol.

    PubMed

    Metz, Gerlinde A; Gonzalez, Claudia L R; Piecharka, Dionne M; Whishaw, Ian Q

    2003-06-16

    Low doses of alcohol impair movement and reduce anxiety. Most assessments of movement under ethyl alcohol (alcohol) in the rat have been tests of whole body movements, however. There has been no examination of the effects of alcohol on skilled limb movements, such as reaching for food with a forelimb. This was the purpose of the present study. Rats were trained to reach through a slot of a box with a forelimb in order to obtain a food pellet located on an external shelf. Once asymptotic performance was achieved, rats were given alcohol (20 ml of 8, 12 or 20% (v/v) solution) in separate tests to establish a relationship between alcohol ingestion and skilled reaching performance. Acute treatment with all doses of alcohol impaired postural support, but doses of 8 and 12% alcohol improved skilled reaching success. Qualitative analysis of the movements used for reaching at doses of 8 and 12% indicated that some limb components of the reaching movement were also impaired, perhaps secondarily due to impaired posture. In contrast, the reaching success of rats with unilateral dopamine depletion, induced with the neurotoxin 6-hydroxydopamine (6-OHDA) in the nigrostriatal bundle, was impaired by the same dose of alcohol that improved reaching success in control rats. The finding of improved success in reaching associated with reduced postural support in normal rats suggests a differential action of alcohol on movement subsystems underlying posture relative to skilled movement that depends upon an intact dopaminergic system. The results are also discussed with respect to the relationship of subsystems of movement and anxiety.

  9. Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains.

    PubMed

    Walker, Brendan M; Drimmer, David A; Walker, Jennifer L; Liu, Tianmin; Mathé, Aleksander A; Ehlers, Cindy L

    2010-09-01

    Depressive symptoms in alcohol-dependent individuals are well-recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol induced. To contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 h on/10 h off) or air exposure for 2 weeks and were then tested at three time points corresponding to acute withdrawal (8-12 h into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five-min FST consisted of latency to immobility, swim time, immobility time, and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors; for instance, decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60-day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared with the control animals, and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain. Copyright © 2010 Elsevier Inc. All rights reserved.

  10. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish.

    PubMed

    Li, Xiang; Li, Xu; Li, Yi-Xiang; Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an "inverted V" dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure.

  11. The Difference between Anxiolytic and Anxiogenic Effects Induced by Acute and Chronic Alcohol Exposure and Changes in Associative Learning and Memory Based on Color Preference and the Cause of Parkinson-Like Behaviors in Zebrafish

    PubMed Central

    Zhang, Yuan; Chen, Di; Sun, Ming-Zhu; Zhao, Xin; Chen, Dong-Yan; Feng, Xi-Zeng

    2015-01-01

    We describe an interdisciplinary comparison of the effects of acute and chronic alcohol exposure in terms of their disturbance of light, dark and color preferences and the occurrence of Parkinson-like behavior in zebrafish through computer visual tracking, data mining, and behavioral and physiological analyses. We found that zebrafish in anxiolytic and anxious states, which are induced by acute and chronic repeated alcohol exposure, respectively, display distinct emotional reactions in light/dark preference tests as well as distinct learning and memory abilities in color-enhanced conditional place preference (CPP) tests. Additionally, compared with the chronic alcohol (1.0%) treatment, acute alcohol exposure had a significant, dose-dependent effect on anxiety, learning and memory (color preference) as well as locomotive activities. Acute exposure doses (0.5%, 1.0%, and 1.5%) generated an “inverted V” dose-dependent pattern in all of the behavioral parameters, with 1.0% having the greatest effect, while the chronic treatment had a moderate effect. Furthermore, by measuring locomotive activity, learning and memory performance, the number of dopaminergic neurons, tyrosine hydroxylase expression, and the change in the photoreceptors in the retina, we found that acute and chronic alcohol exposure induced varying degrees of Parkinson-like symptoms in zebrafish. Taken together, these results illuminated the behavioral and physiological mechanisms underlying the changes associated with learning and memory and the cause of potential Parkinson-like behaviors in zebrafish due to acute and chronic alcohol exposure. PMID:26558894

  12. Behavioral, biological, and chemical perspectives on targeting CRF1 receptor antagonists to treat alcoholism

    PubMed Central

    Zorrilla, Eric P.; Heilig, Markus; de Wit, Harriet; Shaham, Yavin

    2013-01-01

    Background Alcohol use disorders are chronic disabling conditions for which existing pharmacotherapies have only modest efficacy. In the present review, derived from the 2012 Behavior, Biology and Chemistry “Translational Research in Addiction” symposium, we summarize the anti-relapse potential of corticotropin-releasing factor type 1 (CRF1) receptor antagonists to reduce negative emotional symptoms of acute and protracted alcohol withdrawal and stress-induced relapse to alcohol seeking. Methods We review the biology of CRF1 systems, the activity of CRF1 receptor antagonists in animal models of anxiolytic and antidepressant activity, and experimental findings in alcohol addiction models. We also update the clinical trial status of CRF1 receptor antagonists, including pexacerfont (BMS-562086), emicerfont (GW876008), verucerfont (GSK561679), CP316311, SSR125543A, R121919/NBI30775, R317573/19567470/CRA5626, and ONO-2333Ms. Finally, we discuss the potential heterogeneity and pharmacogenomics of CRF1 receptor pharmacotherapy for alcohol dependence. Results The evidence suggests that brain penetrant-CRF1 receptor antagonists have therapeutic potential for alcohol dependence. Lead compounds with clinically desirable pharmacokinetic properties now exist, and longer receptor residence rates (i.e., slow dissociation) may predict greater CRF1 receptor antagonist efficacy. Functional variants in genes that encode CRF system molecules, including polymorphisms in Crhr1 (rs110402, rs1876831, rs242938) and Crhbp genes (rs10055255, rs3811939) may promote alcohol seeking and consumption by altering basal or stress-induced CRF system activation. Conclusions Ongoing clinical trials with pexacerfont and verucerfont in moderately to highly severe dependent anxious alcoholics may yield insight as to the role of CRF1 receptor antagonists in a personalized medicine approach to treat drug or alcohol dependence. PMID:23294766

  13. Voluntary Co-Consumption of Alcohol and Nicotine: Effects of Abstinence, Intermittency, and Withdrawal in Mice

    PubMed Central

    O’Rourke, Kyu Y.; Touchette, Jillienne C.; Hartell, Elizabeth C.; Bade, Elizabeth J.; Lee, Anna M.

    2018-01-01

    Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction. PMID:27342124

  14. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    NASA Astrophysics Data System (ADS)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  15. Effect of the market withdrawal of carisoprodol on use of other prescribed drugs with abuse potential.

    PubMed

    Bramness, J G; Furu, K; Skurtveit, S; Engeland, A

    2012-03-01

    Carisoprodol, a centrally acting muscle relaxant indicated for acute lower back pain, has been available in Europe and the United States since 1959. Studies indicating increased risk of abuse or addiction led to withdrawal of the drug from the market in Norway and other EU countries in 2008. In this nationwide longitudinal prescription study of 53,116 individuals in Norway, previous users of carisoprodol switched, to a limited extent, to other prescribed drugs with abuse potential after the withdrawal.

  16. Alcohol use disorders in pregnancy.

    PubMed

    DeVido, Jeffrey; Bogunovic, Olivera; Weiss, Roger D

    2015-01-01

    Alcohol use disorders (AUDs) are less prevalent in pregnant women than in nonpregnant women, but these disorders can create a host of clinical challenges when encountered. Unfortunately, little evidence is available to guide clinical decision making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but it remains controversial as to the volume of alcohol consumption that correlates with these consequences. Likewise, little evidence is available to support the use of particular pharmacologic interventions for AUDs during pregnancy or to guide the management of alcohol detoxification in pregnant women. The use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Nevertheless, despite the lack of robust data to guide management of AUDs in pregnancy, clinicians need to make management decisions when confronted with these challenging situations. In that context, this article reviews the epidemiology of AUDs in pregnancy and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, with the goal of informing clinicians about what is known about managing these co-occurring conditions.

  17. Alcohol Use Disorders in Pregnancy

    PubMed Central

    DeVido, Jeffrey; Bogunovic, Olivera; Weiss, Roger D.

    2015-01-01

    Alcohol use disorders (AUD) during pregnancy are less prevalent than in non-pregnant women, but they can create a host of clinical challenges when encountered. Unfortunately, there is little research information available to guide clinical decision-making in this population. Drinking alcohol during pregnancy can have negative consequences on both fetus and mother, but there is controversy regarding the volume of alcohol consumption that correlates with these consequences. There is little evidence to support the use of pharmacologic interventions for AUD during pregnancy. Similarly, there are few data to guide management of alcohol detoxification in pregnant women, and the use of benzodiazepines (the mainstay of most alcohol detoxification protocols) in pregnant women is controversial. Despite a lack of robust data to guide management of AUDs in pregnancy, clinicians must nonetheless make management decisions when confronted with these challenging situations. Therefore, this paper reviews the epidemiology of AUDs in pregnancy, and the pharmacologic management of both AUDs and alcohol withdrawal in pregnant women, to better inform clinicians about what is known about managing these co-occurring conditions. PMID:25747924

  18. Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment.

    PubMed

    Zois, E; Vollstädt-Klein, S; Hoffmann, S; Reinhard, I; Charlet, K; Beck, A; Jorde, A; Kirsch, M; Walter, H; Heinz, A; Kiefer, F

    2017-10-01

    Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Understanding the alcohol harm paradox: an analysis of sex- and condition-specific hospital admissions by socio-economic group for alcohol-associated conditions in England.

    PubMed

    Sadler, Susannah; Angus, Colin; Gavens, Lucy; Gillespie, Duncan; Holmes, John; Hamilton, Jean; Brennan, Alan; Meier, Petra

    2017-05-01

    In many countries, conflicting gradients in alcohol consumption and alcohol-associated mortality have been observed. To understand this 'alcohol harm paradox' we analysed the socio-economic gradient in alcohol-associated hospital admissions to test whether it was greater in conditions which were: (1) chronic (associated with long-term drinking) and partially alcohol-attributable, (2) chronic and wholly alcohol-attributable, (3) acute (associated with intoxication) and partially alcohol-attributable and (4) acute and wholly alcohol-attributable. Our aim was to clarify how (1) drinking patterns (e.g. intoxication linked to acute admissions or dependence linked to chronic conditions) and (2) non-alcohol causes (e.g. smoking and poor diet which are risks for partially alcohol-attributable conditions) contribute to the paradox. Regression analysis testing the modifying effects of condition-group (1-4 above) and sex on the relationship between area-based deprivation and admissions. England, April 2010-March 2013. A total of 9 239 629 English hospital admissions where a primary or secondary cause was one of 36 alcohol-associated conditions. Admissions by condition and deciles of Index of Multiple Deprivation (IMD). Socio-economic gradient measured as the relative index of inequality (RII, the slope of a linear regression of IMD on admissions adjusted for overall admission rate). Conditions were categorized by ICD-10 code. A socio-economic gradient in hospitalizations was seen for all conditions, except partially attributable chronic conditions. The gradient was significantly steeper for conditions which were wholly attributable to alcohol and for acute conditions than for conditions partially alcohol-attributable and for chronic conditions. Gradients were steeper for men than for women in cases of wholly alcohol attributable conditions. There is a socio-economic gradient in English hospital admission for most alcohol-associated conditions. The greatest inequalities are in

  20. Ketamine and MAG Lipase Inhibitor-Dependent Reversal of Evolving Depressive-Like Behavior During Forced Abstinence From Alcohol Drinking.

    PubMed

    Holleran, Katherine M; Wilson, Hadley H; Fetterly, Tracy L; Bluett, Rebecca J; Centanni, Samuel W; Gilfarb, Rachel A; Rocco, Lauren E R; Patel, Sachin; Winder, Danny G

    2016-07-01

    Although alcoholism and depression are highly comorbid, treatment options that take this into account are lacking, and mouse models of alcohol (ethanol (EtOH)) intake-induced depressive-like behavior have not been well established. Recent studies utilizing contingent EtOH administration through prolonged two-bottle choice access have demonstrated depression-like behavior following EtOH abstinence in singly housed female C57BL/6J mice. In the present study, we found that depression-like behavior in the forced swim test (FST) is revealed only after a protracted (2 weeks), but not acute (24 h), abstinence period. No effect on anxiety-like behavior in the EPM was observed. Further, we found that, once established, the affective disturbance is long-lasting, as we observed significantly enhanced latencies to approach food even 35 days after ethanol withdrawal in the novelty-suppressed feeding test (NSFT). We were able to reverse affective disturbances measured in the NSFT following EtOH abstinence utilizing the N-methyl D-aspartate receptor (NMDAR) antagonist and antidepressant ketamine but not memantine, another NMDAR antagonist. Pretreatment with the monoacylglycerol (MAG) lipase inhibitor JZL-184 also reduced affective disturbances in the NSFT in ethanol withdrawn mice, and this effect was prevented by co-administration of the CB1 inverse agonist rimonabant. Endocannabinoid levels were decreased within the BLA during abstinence compared with during drinking. Finally, we demonstrate that the depressive behaviors observed do not require a sucrose fade and that this drinking paradigm may favor the development of habit-like EtOH consumption. These data could set the stage for developing novel treatment approaches for alcohol-withdrawal-induced mood and anxiety disorders.

  1. Alcohol dependence as a chronic pain disorder

    PubMed Central

    Egli, Mark; Koob, George F.; Edwards, Scott

    2013-01-01

    Dysregulation of pain neurocircuitry and neurochemistry has been increasingly recognized as playing a critical role in a diverse spectrum of diseases including migraine, fibromyalgia, depression, and PTSD. Evidence presented here supports the hypothesis that alcohol dependence is among the pathologies arising from aberrant neurobiological substrates of pain. In this review, we explore the possible influence of alcohol analgesia and hyperalgesia in promoting alcohol misuse and dependence. We examine evidence that neuroanatomical sites involved in the negative emotional states of alcohol dependence also play an important role in pain transmission and may be functionally altered under chronic pain conditions. We also consider possible genetic links between pain transmission and alcohol dependence. We propose an allostatic load model in which episodes of alcohol intoxication and withdrawal, traumatic stressors, and injury are each capable of dysregulating an overlapping set of neural substrates to engender sensory and affective pain states that are integral to alcohol dependence and comorbid conditions such as anxiety, depression, and chronic pain. PMID:22975446

  2. Neuropeptide Y Opposes Alcohol Effects on GABA Release in Amygdala and Blocks the Transition to Alcohol Dependence

    PubMed Central

    Gilpin, Nicholas W.; Misra, Kaushik; Herman, Melissa A.; Cruz, Maureen T.; Koob, George F.; Roberto, Marisa

    2011-01-01

    Background During the transition to alcohol and drug addiction, neuromodulator systems in the extended amygdala are recruited to mediate aspects of withdrawal and relapse via convergence on inhibitory GABA neurons in central amygdala (CeA). Methods This study investigated the role of neuropeptide Y (NPY) in excessive alcohol drinking by making rats dependent on alcohol via alcohol vapor inhalation. This study also utilized intracellular and whole-cell recording techniques to determine the effects of NPY on GABAergic inhibitory transmission in CeA, synaptic mechanisms involved in these NPY effects, and NPY interactions with alcohol in the CeA of alcohol-naïve and alcohol-dependent rats. Results Chronic NPY treatment blocked excessive operant alcohol-reinforced responding associated with alcohol dependence, as well as gradual increases in alcohol responding by intermittently tested non-dependent controls. NPY decreased baseline GABAergic transmission and reversed alcohol-induced enhancement of inhibitory transmission in CeA by suppressing GABA release via actions at presynaptic Y2 receptors. Conclusions These results highlight NPY modulation of GABAergic signaling in central amygdala as a promising pharmacotheraputic target for the treatment of alcoholism. GABA neurons in the CeA likely constitute a major point of convergence for neuromodulator systems recruited during the transition to alcohol dependence. PMID:21459365

  3. Corticotropin-releasing factor (CRF) and α 2 adrenergic receptors mediate heroin withdrawal-potentiated startle in rats.

    PubMed

    Park, Paula E; Vendruscolo, Leandro F; Schlosburg, Joel E; Edwards, Scott; Schulteis, Gery; Koob, George F

    2013-09-01

    Anxiety is one of the early symptoms of opioid withdrawal and contributes to continued drug use and relapse. The acoustic startle response (ASR) is a component of anxiety that has been shown to increase during opioid withdrawal in both humans and animals. We investigated the role of corticotropin-releasing factor (CRF) and norepinephrine (NE), two key mediators of the brain stress system, on acute heroin withdrawal-potentiated ASR. Rats injected with heroin (2 mg/kg s.c.) displayed an increased ASR when tested 4 h after heroin treatment. A similar increase in ASR was found in rats 10-20 h into withdrawal from extended access (12 h) to i.v. heroin self-administration, a model that captures several aspects of heroin addiction in humans. Both the α 2 adrenergic receptor agonist clonidine (10 μg/kg s.c.) and CRF1 receptor antagonist N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP; 20 mg/kg s.c.) blocked heroin withdrawal-potentiated startle. To investigate the relationship between CRF1 and α 2 adrenergic receptors in the potentiation of the ASR, we tested the effect of MPZP on yohimbine (1.25 mg/kg s.c.)-potentiated startle and clonidine on CRF (2 μg i.c.v.)-potentiated startle. Clonidine blocked CRF-potentiated startle, whereas MPZP partially attenuated but did not reverse yohimbine-potentiated startle, suggesting that CRF may drive NE release to potentiate startle. These results suggest that CRF1 and α 2 receptors play an important role in the heightened anxiety-like behaviour observed during acute withdrawal from heroin, possibly via CRF inducing the release of NE in stress-related brain regions.

  4. Effectiveness of inpatient withdrawal and residential rehabilitation interventions for alcohol use disorder: A national observational, cohort study in England.

    PubMed

    Eastwood, Brian; Peacock, Amy; Millar, Tim; Jones, Andrew; Knight, Jonathan; Horgan, Patrick; Lowden, Tim; Willey, Peter; Marsden, John

    2018-05-01

    This was a national English observational cohort study to estimate the effectiveness of inpatient withdrawal (IW) and residential rehabilitation (RR) interventions for alcohol use disorder (AUD) using administrative data. All adults commencing IW and/or RR intervention for AUD between April 1, 2014 and March 31, 2015 reported to the National Drug Treatment Monitoring System (n=3812). The primary outcome was successful completion of treatment within 12months of commencement, with no re-presentation (SCNR) in the subsequent six months, analysed by multi-level, mixed effects, multivariable logistic regression. The majority (70%, n=2682) received IW in their index treatment journey; one-quarter (24%, n=915) received RR; 6% (n=215) received both. Of treatment leavers, 59% achieved the SCNR outcome (IW: 57%; RR: 64%; IW/RR: 57%). Positive outcome for IW was associated with older age, being employed, and receiving community-based treatment prior to and subsequent to IW. Patients with housing problems were less likely to achieving the outcome. Positive outcome for RR was associated with paid employment, self/family/peer referral, longer duration of RR treatment, and community-based treatment following discharge. Community-based treatment prior to entering RR, and receiving IW during the same treatment journey as RR, were associated with lower likelihood of SCNR. In this first national effectiveness study of AUD in the English public treatment system for alcohol-use disorders, 59% of patients successfully completed treatment within 12months and did not represent for more treatment within six months. Longer duration of treatment and provision of structured continuing care is associated with better treatment outcomes. Copyright © 2018. Published by Elsevier Inc.

  5. [An examination of the determinants of social withdrawal and affinity for social withdrawal].

    PubMed

    Watanabe, Asami; Matsui, Yutaka; Takatsuka, Yusuke

    2010-12-01

    This study examined the determinants of social withdrawal using data from a survey by the Tokyo Metropolitan Government Office for Youth Affairs and Public Safety (2008). In addition, this study identified young people who showed an affinity for social withdrawal although they were not in a state of withdrawal, and examined the determinants of an affinity for social withdrawal. The results of stepwise discriminant analysis showed that factors such as social phobia, depression, violence, and emotional bonds with family differentiated between the general youth group and the social withdrawal group and the "affinity group". Social phobia, violence, and refusal to be interfered in self-decision making differentiated between the social withdrawal group and the "affinity group". This study shows that an "affinity group" should be cared as well as an actual withdrawal group.

  6. The prognostic value of acute-on-chronic liver failure during the course of severe alcoholic hepatitis.

    PubMed

    Sersté, Thomas; Cornillie, Alexia; Njimi, Hassane; Pavesi, Marco; Arroyo, Vicente; Putignano, Antonella; Weichselbaum, Laura; Deltenre, Pierre; Degré, Delphine; Trépo, Eric; Moreno, Christophe; Gustot, Thierry

    2018-03-08

    A better identification of factors predicting death is needed in alcoholic hepatitis (AH). Acute-on-chronic liver failure (ACLF) occurs during the course of liver disease and can be identified when AH is diagnosed (prevalent ACLF [pACLF]) or during follow-up (incidental ACLF [iACLF]). This study analyzed the impact of ACLF on outcomes in AH and the role of infection on the onset of ACLF and death. Patients admitted from July 2006 to July 2015 suffering from biopsy-proven severe (s)AH with a Maddrey discriminant function (mDF) ≥32 were included. Infectious episodes, ACLF, and mortality were assessed during a 168-day follow-up period. Results were validated on an independent cohort. One hundred sixty-five patients were included. Mean mDF was 66.3 ± 20.7 and mean model for end-stage liver disease score was 26.8 ± 7.4. The 28-day cumulative incidence of death (CID) was 31% (95% CI 24-39%). Seventy-nine patients (47.9%) had pACLF. The 28-day CID without pACLF and with pACLF-1, pACLF-2, and pACLF-3 were 10.4% (95% CI 5.1-18.0), 30.8% (95% CI 14.3-49.0), 58.3% (95% CI 35.6-75.5), and 72.4% (95% CI 51.3-85.5), respectively, p <0.0001. Twenty-nine patients (17.5%) developed iACLF. The 28-day relative risk of death in patients developing iACLF was 41.87 (95% CI 5.2-335.1; p <0.001). A previous infection was the only independent risk factor for developing iACLF during the follow-up. Prevalence, incidence, and impact on prognosis of ACLF were confirmed in a validation cohort of 97 patients with probable sAH. ACLF is frequent during the course of sAH and is associated with high mortality. Infection strongly predicts the development of ACLF in this setting. In patients with chronic liver disease, an acute deterioration of liver function combined with single or multiple organ failures is known as acute-on-chronic liver failure. This study shows that acute-on-chronic liver failure is frequent during the course of severe alcoholic hepatitis. In severe alcoholic

  7. The effects of moderate alcohol concentrations on driving and cognitive performance during ascending and descending blood alcohol concentrations.

    PubMed

    Starkey, Nicola J; Charlton, Samuel G

    2014-07-01

    Alcohol has an adverse effect on driving performance; however, the effects of moderate doses on different aspects of the driving task are inconsistent and differ across the intoxication curve. This research aimed to investigate driving and cognitive performance asymmetries (acute tolerance and acute protracted error) accompanying the onset and recovery from moderate alcohol consumption. Sixty-one participants received a placebo, medium (target blood alcohol concentration [BAC] 0.05 mg/ml) or high (target BAC 0.08 mg/ml) dose of alcohol. Participants completed a simulated drive, cognitive tests and subjective rating scales five times over a 3.5 h period. When ascending and descending BACs (0.05 and 0.09 mg/ml) were compared participants' self-ratings of intoxication and willingness to drive showed acute tolerance. Acute protracted errors were observed for response speed, maze learning errors, time exceeding the speed limit and exaggerated steering responses to hazards. Participants' estimates of their level of intoxication were poorly related to their actual BAC levels (and hence degree of impairment), and various aspects of driving and cognitive performance worsened during descending BACs. This indicates that drivers are not good at judging their fitness to drive after drinking only moderate amounts of alcohol and suggests an important focus for public education regarding alcohol and driving. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Treatment for amphetamine withdrawal.

    PubMed

    Shoptaw, Steven J; Kao, Uyen; Heinzerling, Keith; Ling, Walter

    2009-04-15

    Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different. To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes. MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles. All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms. Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes. Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms. No medication is effective for treatment of amphetamine

  9. Acute and subchronic administration of anandamide or oleamide increases REM sleep in rats.

    PubMed

    Herrera-Solís, Andrea; Vásquez, Khalil Guzmán; Prospéro-García, Oscar

    2010-03-01

    Anandamide and oleamide, induce sleep when administered acutely, via the CB1 receptor. Their subchronic administration must be tested to demonstrate the absence of tolerance to this effect, and that the sudden withdrawal of these endocannabinoids (eCBs) does not affect sleep negatively. The sleep-waking cycle of rats was evaluated for 24h, under the effect of an acute or subchronic administration of eCBs, and during sudden eCBs withdrawal. AM251, a CB1 receptor antagonist (CB1Ra) was utilized to block eCBs effects. Our results indicated that both acute and subchronic administration of eCBs increase REMS. During eCBs withdrawal, rats lack the expression of an abstinence-like syndrome. AM251 was efficacious to prevent REMS increase caused by both acute and subchronic administration of these eCBs, suggesting that this effect is mediated by the CB1 receptor. Our data further support a role of the eCBs in REMS regulation. (c) 2009 Elsevier Inc. All rights reserved.

  10. The effect of prior alcohol consumption on the ataxic response to alcohol in high-alcohol preferring mice

    PubMed Central

    Fritz, Brandon M.; Boehm, Stephen L.

    2014-01-01

    We have previously shown that ethanol-naïve high-alcohol preferring (HAP) mice, genetically predis-posed to consume large quantities of alcohol, exhibited heightened sensitivity and more rapid acute functional tolerance (AFT) to alcohol-induced ataxia compared to low-alcohol preferring mice. The goal of the present study was to evaluate the effect of prior alcohol self-administration on these responses in HAP mice. Naïve male and female adult HAP mice from the second replicate of selection (HAP2) underwent 18 days of 24-h, 2-bottle choice drinking for 10% ethanol vs. water, or water only. After 18 days of fluid access, mice were tested for ataxic sensitivity and rapid AFT following a 1.75 g/kg injection of ethanol on a static dowel apparatus in Experiment 1. In Experiment 2, a separate group of mice was tested for more protracted AFT development using a dual-injection approach where a second, larger (2.0 g/kg) injection of ethanol was given following the initial recovery of performance on the task. HAP2 mice that had prior access to alcohol exhibited a blunted ataxic response to the acute alcohol challenge, but this pre-exposure did not alter rapid within-session AFT capacity in Experiment 1 or more protracted AFT capacity in Experiment 2. These findings suggest that the typically observed increase in alcohol consumption in these mice may be influenced by ataxic functional tolerance development, but is not mediated by a greater capacity for ethanol exposure to positively influence within-session ataxic tolerance. PMID:25454537

  11. Opiate and opioid withdrawal

    MedlinePlus

    ... opiate withdrawal; Oxycontin - opiate withdrawal; Hydrocodone - opiate withdrawal; Detox - opiates; Detoxification - opiates ... facilities set up to help people with detoxification (detox). In a regular hospital, if symptoms are severe. ...

  12. Alcohol acutely enhances decoding of positive emotions and emotional concern for positive stimuli and facilitates the viewing of sexual images.

    PubMed

    Dolder, Patrick C; Holze, Friederike; Liakoni, Evangelia; Harder, Samuel; Schmid, Yasmin; Liechti, Matthias E

    2017-01-01

    Social cognition influences social interactions. Alcohol reportedly facilitates social interactions. However, the acute effects of alcohol on social cognition are relatively poorly studied. We investigated the effects of alcoholic or non-alcoholic beer on emotion recognition, empathy, and sexual arousal using the dynamic face emotion recognition task (FERT), Multifaceted Empathy Test (MET), and Sexual Arousal Task (SAT) in a double-blind, random-order, cross-over study in 60 healthy social drinkers. We also assessed subjective effects using visual analog scales (VASs), blood alcohol concentrations, and plasma oxytocin levels. Alcohol increased VAS ratings of stimulated, happy, talkative, open, and want to be with others. The subjective effects of alcohol were greater in participants with higher trait inhibitedness. Alcohol facilitated the recognition of happy faces on the FERT and enhanced emotional empathy for positive stimuli on the MET, particularly in participants with low trait empathy. Pictures of explicit sexual content were rated as less pleasant than neutral pictures after non-alcoholic beer but not after alcoholic beer. Explicit sexual pictures were rated as more pleasant after alcoholic beer compared with non-alcoholic beer, particularly in women. Alcohol did not alter the levels of circulating oxytocin. Alcohol biased emotion recognition toward better decoding of positive emotions and increased emotional concern for positive stimuli. No support was found for a modulatory role of oxytocin. Alcohol also facilitated the viewing of sexual images, consistent with disinhibition, but it did not actually enhance sexual arousal. These effects of alcohol on social cognition likely enhance sociability. www.clinicaltrials.gov/ct2/show/NCT02318823.

  13. Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lai, H.; Prather, P.L.

    1990-02-26

    Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats weremore » trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.« less

  14. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    ClinicalTrials.gov

    2018-02-21

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  15. GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome

    PubMed Central

    Busardò, Francesco P.; Jones, Alan W.

    2015-01-01

    The illicit recreational drug of abuse, γ-hydroxybutyrate (GHB) is a potent central nervous system depressant and is often encountered during forensic investigations of living and deceased persons. The sodium salt of GHB is registered as a therapeutic agent (Xyrem®), approved in some countries for the treatment of narcolepsy-associated cataplexy and (Alcover®) is an adjuvant medication for detoxification and withdrawal in alcoholics. Trace amounts of GHB are produced endogenously (0.5-1.0 mg/L) in various tissues, including the brain, where it functions as both a precursor and a metabolite of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). Available information indicates that GHB serves as a neurotransmitter or neuromodulator in the GABAergic system, especially via binding to the GABA-B receptor subtype. Although GHB is listed as a controlled substance in many countries abuse still continues, owing to the availability of precursor drugs, γ-butyrolactone (GBL) and 1,4-butanediol (BD), which are not regulated. After ingestion both GBL and BD are rapidly converted into GHB (t½ ~1 min). The Cmax occurs after 20-40 min and GHB is then eliminated from plasma with a half-life of 30-50 min. Only about 1-5% of the dose of GHB is recoverable in urine and the window of detection is relatively short (3-10 h). This calls for expeditious sampling when evidence of drug use and/or abuse is required in forensic casework. The recreational dose of GHB is not easy to estimate and a concentration in plasma of ~100 mg/L produces euphoria and disinhibition, whereas 500 mg/L might cause death from cardiorespiratory depression. Effective antidotes to reverse the sedative and intoxicating effects of GHB do not exist. The poisoned patients require supportive care, vital signs should be monitored and the airways kept clear in case of emesis. After prolonged regular use of GHB tolerance and dependence develop and abrupt cessation of drug use leads to unpleasant

  16. Withdrawal Method (Coitus Interruptus)

    MedlinePlus

    Withdrawal method (coitus interruptus) Overview The withdrawal method of contraception, also known as coitus interruptus, is the practice of withdrawing the penis from the vagina and away from a woman's external ...

  17. Effects of Nicotine Metabolites on Nicotine Withdrawal Behaviors in Mice.

    PubMed

    Elhassan, Sagi; Bagdas, Deniz; Damaj, M Imad

    2017-06-01

    Rodent studies suggest that nicotine metabolites and minor tobacco alkaloids such as nornicotine and cotinine may promote cigarette smoking by enhancing nicotine rewarding and reinforcing effects. However, there is little information on the effects of these minor tobacco alkaloids on nicotine withdrawal. The present studies were conducted to determine whether the minor tobacco alkaloids nornicotine and cotinine exhibit nicotine-like behavioral effects in a mouse model of spontaneous nicotine withdrawal. Mice were infused with nicotine or saline for 14 days. Experiments were conducted on day 15, 18-24 hours after minipump removal. Ten minutes prior to testing, nicotine-dependent ICR male mice received an acute injection of nicotine (0.05 and 0.5 mg/kg), nornicotine (2.5 and 25 mg/kg), or cotinine (5 and 50 mg/kg) to determine effects on somatic signs, anxiety-like behaviors, and hyperalgesia spontaneous signs of withdrawal. Nicotine and the minor tobacco alkaloid nornicotine, but not cotinine, produced dose-dependent reversal of nicotine withdrawal signs in the mouse. The minor tobacco alkaloid and nicotine metabolite nornicotine at high doses have nicotinic like effects that may contribute to tobacco consumption and dependence. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Final report of the safety assessment of Alcohol Denat., including SD Alcohol 3-A, SD Alcohol 30, SD Alcohol 39, SD Alcohol 39-B, SD Alcohol 39-C, SD Alcohol 40, SD Alcohol 40-B, and SD Alcohol 40-C, and the denaturants, Quassin, Brucine Sulfate/Brucine, and Denatonium Benzoate.

    PubMed

    2008-01-01

    Alcohol Denat. is the generic term used by the cosmetics industry to describe denatured alcohol. Alcohol Denat. and various specially denatured (SD) alcohols are used as cosmetic ingredients in a wide variety of products. Many denaturants have been previously considered, on an individual basis, as cosmetic ingredients by the Cosmetic Ingredient Review (CIR) Expert Panel, whereas others, including Brucine and Brucine Sulfate, Denatonium Benzoate, and Quassin, have not previously been evaluated. Quassin is a bitter alkaloid obtained from the wood of Quassia amara. Quassin has been used as an insect antifeedant and insecticide and several studies demonstrate its effectiveness. At oral doses up to 1000 mg/kg using rats, Quassin was not toxic in acute and short-term tests, but some reversible piloerection, decrease in motor activity, and a partial loss of righting reflex were found in mice at 500 mg/kg. At 1000 mg/kg given intraperitoneally (i.p.), all mice died within 24 h of receiving treatment. In a cytotoxicity test with brine shrimp, 1 mg/ml of Quassin did not possess any cytotoxic or antiplasmodial activity. Quassin administered to rat Leydig cells in vitro at concentrations of 5-25 ng/ml inhibited both the basal and luteinizing hormone (LH)-stimulated testosterone secretion in a dose-related fashion. Quassin at doses up to 2.0 g/kg in drinking water using rats produced no significant effect on the body weights, but the mean weights of the testes, seminal vesicles, and epididymides were significantly reduced, and the weights of the anterior pituitary glands were significantly increased. The sperm counts and levels of LH, follicle-stimulating hormone (FSH), and testosterone were significantly lower in groups treated with Quassin. Brucine is a derivative of 2-hydroxystrychnine. Swiss-Webster mice given Brucine base, 30 ml/kg, had an acute oral LD(50) of 150 mg/kg, with central nervous system depression followed by convulsions and seizures in some cases. In those

  19. Topiramate in opiate withdrawal.

    PubMed

    Zullino, Daniele F; Cottier, Anne-Claude; Besson, Jacques

    2002-10-01

    The alpha2-adrenergic agonist clonidine is the mainly used drug for the opiate withdrawal. Its efficacy and tolerance in treating withdrawal symptoms is, however, suboptimal. The pharmacological profile of topiramate suggests it could be rather valuable for opiate withdrawal, as there is some evidence that topiramate acts, among others, through inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, which play an important role in the withdrawal-induced activation of the locus coeruleus (LC) by glutamate. Three patients undergoing an inpatient opiate detoxification program were treated with topiramate, which achieved a nearly complete control of withdrawal symptoms.

  20. A Social Media-Based Acute Alcohol Consumption Behavior (NekNomination): Case Series in Italian Emergency Departments

    PubMed Central

    Lucchetta, Vittorio; Gaudio, Rosa Maria; Tredese, Alberto; Bergamini, Mauro; Vettore, Gianna; Pietrantonio, Vincenzo; Avato, Francesco Maria; Donato, Daniele; Boemo, Deris Gianni; Nesoti, Maria Vittoria; Snenghi, Rossella

    2018-01-01

    Background NekNomination, also known as NekNominate, Neck and Nominate, or Neck Nomination, is a social network–based drinking game which is thought to have originated in Australia and spread all over the world between 2013 and 2014. Individuals record videos of themselves while rapidly drinking excessive quantities of alcoholic drinks (necking) and then nominate friends to outdo them within 24 hours; the videos are then posted on social media such as Facebook or YouTube. The consequences of this drinking game have been very dangerous; at least 5 people under age 30 years have died after drinking deadly cocktails, and many others have suffered from alcohol intoxication. Objective The goal of the research is to evaluate data about clinically important acute alcohol intoxication among teenagers and young adults and inform and educate the general public, especially parents, teachers, and health workers, about the spreading craze of dangerous Internet-related behavior among today’s teenagers and young people up to the age of 23 years. Methods Patients aged 15 to 23 years with acute alcohol intoxication who came to the emergency department (ED) of 2 major hospitals in Italy from January 1, 2011, to June 30, 2014, were included in this study. Data were retrieved from prehospital and intrahospital medical records and included personal information, methods of intoxication, triage color code, date and time of access to the ED, any relevant signs and symptoms, blood alcohol concentration, and diagnosis at discharge. Results A total of 450 young patients (male 277/450, 61.5%, female 173/450, 38.5%; age 15 to 16 years 15/450, 3.3%, age 17 to 18 years 184/450, 40.9%, age 19 to 23 years 251/450, 55.8%) were recruited. The causes of intoxication were happy hour, binge drinking, NekNominate, eyeballing, other alcoholic games, or a mix of them. Happy hour was found to be more common among the older patients, whereas NekNominate accounted for almost half of the youngest group of

  1. QT prolongation in the newborn and maternal alcoholism.

    PubMed

    Krasemann, Thomas

    2004-10-01

    I discuss a newborn whose mother is addicted to alcohol. On the third day of life, the newborn was found to have ventricular tachycardia. After spontaneous termination of the abnormal rhythm, the duration of the corrected QT interval was 0.48 s. During the next days, the duration of the interval normalized, and has now remained stable for 5 years. I conclude that the so-called "alcohol withdrawal syndrome of the newborn" might cause postnatal prolongation of the QT interval.

  2. The Cannabis Withdrawal Scale development: patterns and predictors of cannabis withdrawal and distress.

    PubMed

    Allsop, David J; Norberg, Melissa M; Copeland, Jan; Fu, Shanlin; Budney, Alan J

    2011-12-01

    Rates of treatment seeking for cannabis are increasing, and relapse is common. Management of cannabis withdrawal is an important intervention point. No psychometrically sound measure for cannabis withdrawal exists, and as a result treatment developments cannot be optimally targeted. The aim is to develop and test the psychometrics of the Cannabis Withdrawal Scale and use it to explore predictors of cannabis withdrawal. A volunteer sample of 49 dependent cannabis users provided daily scores on the Cannabis Withdrawal Scale during a baseline week and 2 weeks of abstinence. Internal reliability (Cronbach's alpha=0.91), test-retest stability (average intra-class correlation=0.95) and content validity analysis show that the Cannabis Withdrawal Scale has excellent psychometric properties. Nightmares and/or strange dreams was the most valid item (Wald χ²=105.6, P<0.0001), but caused relatively little associated distress (Wald χ²=25.11, P=0.03). Angry outbursts were considered intense (Wald χ²=73.69, P<0.0001) and caused much associated distress (Wald χ²=45.54, P<0.0001). Trouble getting to sleep was also an intense withdrawal symptom (Wald χ²=42.31, P<0.0001) and caused significant associated distress (Wald χ²=47.76, P<0.0001). Scores on the Severity of Dependence Scale predicted cannabis withdrawal. The Cannabis Withdrawal Scale can be used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Low molecular-weight gel fraction of Aloe vera exhibits gastroprotection by inducing matrix metalloproteinase-9 inhibitory activity in alcohol-induced acute gastric lesion tissues.

    PubMed

    Park, Chul-Hong; Son, Hyeong-U; Yoo, Chi-Yeol; Lee, Sang-Han

    2017-12-01

    Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.

  4. Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

    PubMed Central

    Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

    2013-01-01

    The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

  5. ATTENUATION OF ALCOHOL CONSUMPTION BY MDMA (ECSTASY) IN TWO STRAINS OF ALCOHOL PREFERRING RATS

    EPA Science Inventory

    Alcohol preference and manifestation of alcoholism are thought by many to be associated with serotonin (5-HT) dysfunction in the brain. hus, experiments were performed to determine the effect of acute and sub-chronic administration (s.c.) of (+/-)3,4-methylenedioxymethamphetamine...

  6. [Alcohol intoxication in old age].

    PubMed

    Menecier, Pascal; Rotheval, Loetita

    Acute alcohol intoxication occurs in elderly subjects. Drunkenness appears in banal clinical forms in geriatrics: falls, dizziness or confusion. Elderly people are more vulnerable to alcohol and need less alcohol to become intoxicated. Age does not exclude the possibility of receiving alcohol addiction treatment. Broaching the subject with an elderly person, the day after a drunken episode, is useful and recommended. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Pharmacological therapies for management of opium withdrawal.

    PubMed

    Rahimi-Movaghar, Afarin; Gholami, Jaleh; Amato, Laura; Hoseinie, Leila; Yousefi-Nooraie, Reza; Amin-Esmaeili, Masoumeh

    2018-06-21

    Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium. To assess the effectiveness and safety of various pharmacologic therapies for the management of the acute phase of opium withdrawal. We searched the following sources up to September 2017: CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, regional and national databases (IMEMR, Iranmedex, and IranPsych), main electronic sources of ongoing trials, and reference lists of all relevant papers. In addition, we contacted known investigators to obtain missing data or incomplete trials. Controlled clinical trials and randomised controlled trials on pharmacological therapies, compared with no intervention, placebo, other pharmacologic treatments, different doses of the same drug, and psychosocial intervention, to manage acute withdrawal from opium in a maximum duration of 30 days. We used the standard methodological procedures expected by Cochrane. We included 13 trials involving 1096 participants. No pooled analysis was possible. Studies were carried out in three countries, Iran, India, and Thailand, in outpatient and inpatient settings. The quality of the evidence was generally very low.When the mean of withdrawal symptoms was provided for several days, we mainly focused on day 3. The reason for this was that the highest severity of opium withdrawal is in the second to fourth day.Comparing different pharmacological treatments with each other, clonidine was twice as good as methadone for completion of treatment (risk ratio (RR) 2.01, 95% confidence interval (CI) 1.69 to 2.38; 361 participants, 1 study, low-quality evidence). All the other results showed no differences between the considered drugs: baclofen versus clonidine (RR 1.06, 95% CI 0.63 to 1.80; 66 participants, 1

  8. Fetal Alcohol Syndrome: A Behavioral Teratology.

    ERIC Educational Resources Information Center

    Kavale, Kenneth A.; Karge, Belinda D.

    1986-01-01

    The review examines the literature on the behaviorally teratogenic aspects of Fetal Alcohol Syndrome, including: (1) prevalence of alcohol abuse among women, (2) acute and chronic effects of alcohol on the fetus, (3) genetic susceptibility, (4) neuropathology, (5) correlative conditions, and (6) animal studies. (Author/DB)

  9. Effects of aqueous extracts from Panax ginseng and Hippophae rhamnoides on acute alcohol intoxication: An experimental study using mouse model.

    PubMed

    Wen, Da-Chao; Hu, Xiao-Yu; Wang, Yan-Yan; Luo, Jian-Xing; Lin, Wu; Jia, Ling-Yan; Gong, Xin-Yue

    2016-11-04

    Acute alcohol intoxication (AAI) is a frequent emergency, but therapeutic drugs with superior efficacy and safety are lacking. Panax ginseng (PG) and Hippophae rhamnoides (HR) respectively has a wide application as a complementary therapeutic agent in China for the treatment of AAI and liver injury induced by alcohol. We investigated the effects of aqueous extracts from PG and HR (AEPH) on AAI mice and identified its underlying mechanisms. Models of AAI were induced by intragastric administration of ethanol (8g/kg). Seventy-two Specific pathogen-free (SPF) male Kunming mice were randomly divided into six groups: normal group, positive control group, AEPH of low dosage (100mg/kg) group, AEPH of medium dose (200mg/kg) group, AEPH of high dosage (400mg/kg) group and model group. The mice were treated with metadoxine (MTD, 500mg/kg) and AEPH. Thirty minutes later, the normal group was given normal saline, while the other groups were given ethanol (i.g., 8g/kg). The impact of AEPH was observed. In the same way, another seventy-two Kunming mice were randomly divided into six groups equally. The blood ethanol concentration at 0.5, 1, 1.5, 2, 3 and 6h after ethanol intake was determined by way of gas chromatography. The activity of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and microsomal ethanol oxidase (EO) in liver, and the concentration of β-endorphin (β-EP), leucine-enkephalin (LENK) in the brain were determined by enzyme-linked-immunosorbent serologic assay (ELISA). AEPH markedly prolonged alcohol tolerance time and shortened sober-up time after acute ethanol administration. AEPH decreased blood ethanol levels in six tests after ethanol intake. The 7-day survival rate of AEPH group was obviously superior to model group. AEPH increased the activities of ADH, ALDH, and decreased EO activity in liver. The crucial find was that AEPH markedly decreased β-EP and LENK concentration in the brain. AEPH can markedly increase the levels of ADH, ALDH, decrease

  10. Evolution of Wernicke-Korsakoff syndrome in self-neglecting alcoholics: preliminary results of relation with Wernicke-delirium and diabetes mellitus.

    PubMed

    Wijnia, Jan W; van de Wetering, Ben J M; Zwart, Elles; Nieuwenhuis, K Gerrit A; Goossensen, M Anne

    2012-01-01

    We present a descriptive, retrospective study of initial symptoms, comorbidity, and alcohol withdrawal in 73 alcoholic patients with subsequent Korsakoff syndrome. In 25/73 (35%) of the patients the classic triad of Wernicke's encephalopathy with ocular symptoms, ataxia and confusion, was found. In at least 6/35 (17%) of the initial deliria (95% confidence interval: 10-25%) we observed no other underlying causes, thus excluding other somatic causes, medication, (recent) alcohol withdrawal, or intoxication. We suggest that these deliria may have been representing Wernicke's encephalopathy. A high frequency (15%) of diabetics may reflect a contributing factor of diabetes mellitus in the evolution of the Wernicke-Korsakoff syndrome. Copyright © American Academy of Addiction Psychiatry.

  11. The Alcohol Sensitivity Questionnaire: Evidence for Construct Validity

    PubMed Central

    Fleming, Kimberly A.; Bartholow, Bruce D.; Hilgard, Joseph B.; McCarthy, Denis M.; O’Neill, Susan E.; Steinley, Douglas; Sher, Kenneth J.

    2016-01-01

    Background Variability in sensitivity to the acute effects of alcohol is an important risk factor for the development of alcohol use disorder (AUD). The most commonly used retrospective self-report measure of sensitivity, the Self-Rating of the Effects of Alcohol form (SRE), queries a limited number of alcohol effects and relies on respondents’ ability to recall experiences that might have occurred in the distant past. Here, we investigated the construct validity of an alternative measure that queries a larger number of alcohol effects, the Alcohol Sensitivity Questionnaire (ASQ), and compared it to the SRE in predicting momentary subjective responses to an acute dose of alcohol. Method Healthy young adults (N = 423) completed the SRE and the ASQ and then were randomly assigned to consume either alcohol or a placebo beverage (between-subjects manipulation). Stimulation and sedation (Biphasic Alcohol Effects Scale) and subjective intoxication were measured multiple times after drinking. Results Hierarchical linear models showed that the ASQ reliably predicted each of these outcomes following alcohol but not placebo consumption, provided unique prediction beyond that associated with differences in recent alcohol involvement, and was preferred over the SRE (in terms of model fit) in direct model comparisons of stimulation and sedation. Conclusions The ASQ compared favorably with the better-known SRE in predicting increased stimulation and reduced sedation following an acute alcohol challenge. The ASQ appears to be a valid self-report measure of alcohol sensitivity and therefore holds promise for identifying individuals at-risk for AUD and related problems. PMID:27012527

  12. [Alcoholic ketoacidosis and reversible neurological complications due to hypophosphataemia].

    PubMed

    Fernández López, Ma T; García Bargo, Ma D; Rivero Luis, Ma T; Álvarez Vázquez, P; Saenz Fernández, C A; Mato Mato, J A

    2012-01-01

    A 57-year-old man with chronic alcoholism was admitted to our hospital due to disturbance of consciousness and polyradiculitis. Laboratory examination revealed metabolic acidosis, hypokalemia and hypophosphataemia. Alcoholic ketoacidosis is a common disorder in alcoholic patients. All patients present with a history of heavy alcohol misuse, preceding a bout of particularly excesive intake, which had been terminated by nausea, vomiting and abdominal pain. The most important laboratory results are: normal or low glucose level, metabolic acidosis with a raised anion GAP, low or absent blood alcohol level and urinary ketones. The greatest threats to patients are: hypovolemia, hypokaliemia, hypoglucemia and acidosis. Alcohol abuse may result in a wide range of electrolyte and acid-base disorders including hypophosphataemia, hypomagnesemia, hypocalcemia, hypokalemia, metabolic acidosis and respiratory alkalosis. Disturbance of consciousness in alcoholic patients is observed in several disorders, such drunkenness, Wernicke encephalopathy, alcohol withdrawal syndrome, central pontine myelinolysis, hepatic encephalopathy, hypoglucemia and electrolyte disorders.

  13. Income inequality and alcohol attributable harm in Australia.

    PubMed

    Dietze, Paul M; Jolley, Damien J; Chikritzhs, Tanya N; Clemens, Susan; Catalano, Paul; Stockwell, Tim

    2009-02-25

    There is little research on the relationship between key socioeconomic variables and alcohol related harms in Australia. The aim of this research was to examine the relationship between income inequality and the rates of alcohol-attributable hospitalisation and death at a local-area level in Australia. We conducted a cross sectional ecological analysis at a Local Government Area (LGA) level of associations between data on alcohol caused harms and income inequality data after adjusting for socioeconomic disadvantage and remoteness of LGAs.The main outcome measures used were matched rate ratios for four measures of alcohol caused harm; acute (primarily related to the short term consequences of drinking) and chronic (primarily related to the long term consequences of drinking) alcohol-attributable hospitalisation and acute and chronic alcohol-attributable death. Matching was undertaken using control conditions (non-alcohol-attributable) at an LGA level. A total of 885 alcohol-attributable deaths and 19467 alcohol-attributable hospitalisations across all LGAs were available for analysis. After weighting by the total number of cases in each LGA, the matched rate ratios of acute and chronic alcohol-attributable hospitalisation and chronic alcohol-attributable death were associated with the squared centred Gini coefficients of LGAs. This relationship was evident after adjusting for socioeconomic disadvantage and remoteness of LGAs. For both measures of hospitalisation the relationship was curvilinear; increases in income inequality were initially associated with declining rates of hospitalisation followed by large increases as the Gini coefficient increased beyond 0.15. The pattern for chronic alcohol-attributable death was similar, but without the initial decrease. There was no association between income inequality and acute alcohol-attributable death, probably due to the relatively small number of these types of death. We found a curvilinear relationship between income

  14. 27 CFR 19.534 - Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... use in production of nonbeverage wine and nonbeverage wine products. 19.534 Section 19.534 Alcohol... Withdrawals of spirits for use in production of nonbeverage wine and nonbeverage wine products. Spirits... bonded wine cellar for use in the production of nonbeverage wine and nonbeverage wine products. (Sec. 455...

  15. Response to CPAP Withdrawal in Patients with Mild Versus Severe Obstructive Sleep Apnea/Hypopnea Syndrome

    PubMed Central

    Young, Laura R.; Taxin, Zachary H.; Norman, Robert G.; Walsleben, Joyce A.; Rapoport, David M.; Ayappa, Indu

    2013-01-01

    Background: Patients with obstructive sleep apnea/hypopnea syndrome (OSAHS), even those generally compliant with CPAP therapy, often intermittently discontinue CPAP. Study Objective: Examine the impact of CPAP withdrawal on sleep, sleep disordered breathing (SDB), and daytime function in subjects with varying severity of OSAHS. Patients and Interventions: Forty-two subjects (26M/16 F) with OSAHS (AHI4% = 45.2 ± 35.5/h pretreatment) on CPAP for 4 months were evaluated on the second night of CPAP withdrawal. Sleep architecture, SDB indices, and subjective/objective daytime function were assessed pretreatment, on CPAP therapy, and after CPAP withdrawal. Comparisons were made between pretreatment and CPAP withdrawal for the entire group, and for subgroups of mild/moderate (AHI4% < 30/h, n = 22) and severe (AHI4% > 30/h, n = 20) SDB. Results: Overall, and for mild/moderate subjects, SDB indices returned to pretreatment values on CPAP withdrawal but with fewer apneas and more hypopneas/RERAs. For severe SDB, the event frequency (AI, AHI4%, and RDI) was lower and O2 desaturation was improved on CPAP withdrawal. Across SDB severity, sleep architecture showed lower %REM (15.6% vs 12.9%, P = 0.009) on the CPAP withdrawal compared to pretreatment. Stanford Sleepiness Score, MSLT, and PVT measures were not significantly different between pretreatment and CPAP withdrawal. Conclusions: Over a wide range of SDB severity CPAP withdrawal results in recurrence of SDB, albeit with less severe O2 desaturation. Subjective/objective daytime function returned to pretreatment levels. Sleep architecture changes on CPAP withdrawal (acute SDB) may reflect reduced sleep pressure compared to pretreatment chronic SDB. Our data suggest detrimental effects of even brief withdrawal of CPAP in subjects with both mild and severe OSAHS. Citation: Young LR; Taxin ZH; Norman RG; Walsleben JA; Rapoport DM; Ayappa I. Response to CPAP withdrawal in patients with mild versus severe obstructive sleep apnea

  16. Rapid spontaneous resolution of acute subdural haematoma in a patient with chronic alcoholism.

    PubMed

    Hadjigeorgiou, Georgios; Chamilos, Christos; Petsanas, Adamantios; Vranos, Georgios; Foteas, Pavlos; Spiridakis, Filokypros

    2012-06-01

    Acute subdural haematoma (ASDH) constitutes one of the most critical emergencies in neurosurgery. There are only several reports that show the rapid disappearance of ASDH without surgical intervention. We report a case of a 64-year-old alcoholic man who had a traumatic subdural haematoma after a fall from a height of about eight meters on level ground. The computed tomography (CT) of the brain on admission demonstrated a left parietooccipital ASDH. A follow-up CT scan after 8 hours showed resolution of the hematoma. The patient was discharged 9 days later with no neurological deficit. We discuss the possible mechanisms of the rapid resolution of the ASDH.

  17. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  18. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  19. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  20. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  1. 40 CFR 74.18 - Withdrawal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... opt-in source may request to withdraw from the Acid Rain Program by submitting an administrative... paragraph (f)(1) of this section. (b) Requesting withdrawal. To withdraw from the Acid Rain Program, the...-in source's prior violations. An opt-in source that withdraws from the Acid Rain Program shall comply...

  2. A Social Media-Based Acute Alcohol Consumption Behavior (NekNomination): Case Series in Italian Emergency Departments.

    PubMed

    Barbieri, Stefania; Feltracco, Paolo; Lucchetta, Vittorio; Gaudio, Rosa Maria; Tredese, Alberto; Bergamini, Mauro; Vettore, Gianna; Pietrantonio, Vincenzo; Avato, Francesco Maria; Donato, Daniele; Boemo, Deris Gianni; Nesoti, Maria Vittoria; Snenghi, Rossella

    2018-01-31

    NekNomination, also known as NekNominate, Neck and Nominate, or Neck Nomination, is a social network-based drinking game which is thought to have originated in Australia and spread all over the world between 2013 and 2014. Individuals record videos of themselves while rapidly drinking excessive quantities of alcoholic drinks (necking) and then nominate friends to outdo them within 24 hours; the videos are then posted on social media such as Facebook or YouTube. The consequences of this drinking game have been very dangerous; at least 5 people under age 30 years have died after drinking deadly cocktails, and many others have suffered from alcohol intoxication. The goal of the research is to evaluate data about clinically important acute alcohol intoxication among teenagers and young adults and inform and educate the general public, especially parents, teachers, and health workers, about the spreading craze of dangerous Internet-related behavior among today's teenagers and young people up to the age of 23 years. Patients aged 15 to 23 years with acute alcohol intoxication who came to the emergency department (ED) of 2 major hospitals in Italy from January 1, 2011, to June 30, 2014, were included in this study. Data were retrieved from prehospital and intrahospital medical records and included personal information, methods of intoxication, triage color code, date and time of access to the ED, any relevant signs and symptoms, blood alcohol concentration, and diagnosis at discharge. A total of 450 young patients (male 277/450, 61.5%, female 173/450, 38.5%; age 15 to 16 years 15/450, 3.3%, age 17 to 18 years 184/450, 40.9%, age 19 to 23 years 251/450, 55.8%) were recruited. The causes of intoxication were happy hour, binge drinking, NekNominate, eyeballing, other alcoholic games, or a mix of them. Happy hour was found to be more common among the older patients, whereas NekNominate accounted for almost half of the youngest group of hospitalizations. Eyeballing occurred in

  3. Treatment for amphetamine withdrawal.

    PubMed

    Srisurapanont, M; Jarusuraisin, N; Kittirattanapaiboon, P

    2001-01-01

    Amphetamine withdrawal has been less studied although it is a common problem with a prevalent rate of 87% among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse of amphetamine use. In clinical practice, treatment for cocaine withdrawal has been recommended for the management of amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two substances are not the same. To search and determine risks, benefits, and costs of a variety of treatments for the management of amphetamine withdrawal. Electronic searches of MEDLINE (1966 - December 2000), EMBASE (1980 - February 2001), CINAHL (1982 - January 2001) and Cochrane Controlled Trials Register (Cochrane Library 2000 issue 4) were undertaken. References to the articles obtained by any means were searched. All relevant randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were included. Participants were people with amphetamine withdrawal, diagnosed by any set of criteria. Any kinds of biological and psychological treatments both alone and combined were examined. A variety of outcomes, for example, number of treatment responders, score changes, were considered. Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis in which the dropouts were assigned as participants with the worst outcomes. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess the dichotomous data. The Weighted Mean Difference (WMD) with 95% CI was used to assessed the continuous data. The results of two studies have shown some benefits of amineptine in the treatment of amphetamine withdrawal. Those benefits can be seen in the respects of discontinuation rate and global state, as measured by Clinical Global Impression Scale. However, no direct benefit of amineptine on amphetamine withdrawal symptoms or craving was shown. The evidence about

  4. Withdrawal: Expanding a Key Addiction Construct

    PubMed Central

    2015-01-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. PMID:25744958

  5. The effects of alcohol on spontaneous clearance of acute hepatitis C virus infection in females versus males.

    PubMed

    Tsui, Judith I; Mirzazadeh, Ali; Hahn, Judith A; Maher, Lisa; Bruneau, Julie; Grebely, Jason; Hellard, Margaret; Kim, Arthur Y; Shoukry, Naglaa H; Cox, Andrea L; Prins, Maria; Dore, Gregory J; Lauer, Georg; Lloyd, Andrew R; Page, Kimberly

    2016-12-01

    Approximately one quarter of persons exposed to hepatitis C virus (HCV) will spontaneously clear infection. We undertook this study to investigate the impact of alcohol on likelihood of HCV spontaneous viral clearance stratified by sex groups. Pooled data from an international collaboration of prospective observational studies of incident HIV and HCV infection in high-risk cohorts (the InC3 Study) was restricted to 411 persons (or 560.7 person-years of observation) with documented acute HCV infection and data regarding alcohol use. The predictor of interest was self-reported alcohol use at or after estimated date of incident HCV infection and the outcome was HCV spontaneous clearance. Sex stratified Cox proportional hazards models were used to evaluate the association between alcohol and spontaneous clearance, adjusting for age, race/ethnicity, and IFNL4 genotype. The median age was 28.5 years, 30.4% were women, 87.2% were white, and 71.8% reported alcohol use at or after incident infection. There were 89 (21.6%) cases of spontaneous clearance observed, 39 (31.2%) among women and 50 (17.5%) in men (p<0.01). Overall, spontaneous clearance occurred less frequently among participants who drank alcohol compared to those who did not drink (18.9% v. 28.5%, p=0.03). After adjustment for other covariates, alcohol was significantly and independently associated with lower relative hazards for spontaneous clearance of HCV in women (AHR=0.35; 95% CI: 0.19-0.66; p=0.001) but not in men (AHR=0.63; 95% CI: 0.36-1.09; p=0.10). Results indicate that abstaining from drinking alcohol may increase the likelihood of spontaneous clearance among women. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. The Effects of Alcohol on Spontaneous Clearance of Acute Hepatitis C Virus Infection in Females versus Males

    PubMed Central

    Tsui, Judith I.; Mirzazadeh, Ali; Hahn, Judith A.; Maher, Lisa; Bruneau, Julie; Grebely, Jason; Hellard, Margaret; Kim, Arthur Y.; Shoukry, Naglaa H.; Cox, Andrea L.; Prins, Maria; Dore, Gregory; Lauer, Georg; Lloyd, Andrew; Page, Kimberly

    2016-01-01

    Background Approximately one quarter of persons exposed to hepatitis C virus (HCV) will spontaneously clear infection. We undertook this study to investigate the impact of alcohol on likelihood of HCV spontaneous viral clearance stratified by sex groups. Methods Pooled data from an international collaboration of prospective observational studies of incident HIV and HCV infection in high-risk cohorts (the InC3 Study) was restricted to 411 persons (or 560.7 person-years of observation) with documented acute HCV infection and data regarding alcohol use. The predictor of interest was self-reported alcohol use at or after estimated date of incident HCV infection and the outcome was HCV spontaneous clearance. Sex stratified Cox proportional hazards models were used to evaluate the association between alcohol and spontaneous clearance, adjusting for age, race/ethnicity, and IFNL4 genotype. Results The median age was 28.5 years, 30.4% were women, 87.2% were white, and 71.8% reported alcohol use at or after incident infection. There were 89 (21.6%) cases of spontaneous clearance observed, 39 (31.2%) among women and 50 (17.5%) in men (p<0.01). Overall, spontaneous clearance occurred less frequently among participants who drank alcohol compared to those who did not drink (18.9% v. 28.5%, p=0.03). After adjustment for other covariates, alcohol was significantly and independently associated with lower relative hazards for spontaneous clearance of HCV in women (AHR=0.35; 95% CI: 0.19-0.66; p=0.001) but not in men (AHR=0.63; 95% CI: 0.36-1.09; p=0.10). Conclusion Results indicate that abstaining from drinking alcohol may increase the likelihood of spontaneous clearance among women. PMID:27816863

  7. Characterization of the increased binding of acetaldehyde to red blood cells in alcoholics.

    PubMed

    Hernández-Muñoz, R; Baraona, E; Blacksberg, I; Lieber, C S

    1989-10-01

    Using equilibrium dialysis, we found that acetaldehyde, at the levels commonly occurring after ethanol ingestion, did not bind detectably to plasma proteins, but there was significant binding to red blood cells, more in alcoholics than in nonalcoholics. The binding to red blood cells was inhibited by pyridoxal phosphate and N-ethylmaleimide, suggesting adduction to amino and thiol groups. Binding kinetics were consistent with at least two sites. The one with the highest affinity for acetaldehyde corresponded to hemoglobin. Its affinity and Bmax were not changed in alcoholics, but these binding sites accounted for only 44% of the sites available in the red blood cells of alcoholics and 80% of those in controls. Moreover, this binding was not inhibited by N-ethylmaleimide. There was no detectable binding to red cell ghosts. Nonprotein binding was then assessed by changes in NADH produced by the addition of protein-free fractions of the cells to an alcohol dehydrogenase system in equilibrium; this revealed a second binder of lower affinity, larger capacity and with sensitivity to both inhibitors. This binding (possibly due to thiazolidine formation with cysteine) was enhanced in alcoholics, whose red blood cell cysteine content was doubled. Levels of red blood cell cysteine and acetaldehyde remained high for 2 weeks after withdrawal. Because of the prolonged persistence after withdrawal, these changes may provide new markers of alcoholism.

  8. Pioglitazone attenuates the opioid withdrawal and vulnerability to relapse to heroin seeking in rodents.

    PubMed

    de Guglielmo, Giordano; Kallupi, Marsida; Scuppa, Giulia; Demopulos, Gregory; Gaitanaris, George; Ciccocioppo, Roberto

    2017-01-01

    Relapse to opioids is often driven by the avoidance of the aversive states of opioid withdrawal. We recently demonstrated that activation of peroxisome proliferator-activated receptor gamma (PPARγ) by pioglitazone reduces the motivation for heroin and attenuates its rewarding properties. However, the role of PPARγ in withdrawal and other forms of relapse to heroin is unknown. To further address this issue, we investigated the role of PPARγ on the development and expression of morphine withdrawal in mice and the effect of pioglitazone on several forms of heroin relapse in rats. We induced physical dependence to morphine in mice by injecting morphine twice daily for 6 days. Withdrawal syndrome was precipitated on day 6 with an injection of naloxone. In addition, different groups of rats were trained to self-administer heroin and, after the extinction, the relapse was elicited by cues, priming, or stress. The effect of different doses of pioglitazone was tested on these different paradigms. Data show that chronic and acute administration of pioglitazone attenuates morphine withdrawal symptoms, and these effects are mediated by activation of PPARγ receptors. Activation of PPARγ by pioglitazone also abolishes yohimbine-induced reinstatement of heroin seeking and reduces heroin-induced reinstatement, while it does not affect cue-induced relapse. These findings provide new insights on the role of PPARγ on opioid dependence and suggest that pioglitazone may be useful for the treatment of opioid withdrawal in opioid-addicted individuals.

  9. Statin withdrawal: clinical implications and molecular mechanisms.

    PubMed

    Cubeddu, Luigi X; Seamon, Matthew J

    2006-09-01

    Retrospective analyses of data from the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM), the National Registry of Myocardial Infarction 4, and the Global Registry of Acute Coronary Events (GRACE) trials revealed that the benefits of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) on acute coronary outcomes are rapidly lost and outcomes worsened if statins are discontinued during a patient's hospitalization for an acute coronary syndrome. Withdrawal of statin therapy in the first 24 hours of hospitalization for non-ST-elevation myocardial infarction increased the hospital morbidity and mortality rate versus continued therapy (11.9% vs 5.7%, p<0.01). Data from the Treating New Targets (TNT) study, however, suggested that short-term discontinuation of statin therapy in patients with stable cardiac conditions may not substantially increase the risk of acute coronary syndromes. In patients with acute coronary syndromes who discontinue statins, the rapid increase in risk of an event may result not only from the lost benefits from the therapy, but also from rebound inhibition of vascular protective substances and activation of vascular deleterious substances. Statins inhibit cholesterol synthesis in vascular cells. By reducing levels of isoprenoid intermediates, statins increase the production of nitric oxide and downregulate angiotensin II AT(1) receptors, endothelin-1, vascular inflammatory adhesion molecules, and inflammatory cytokines. These benefits are rapidly lost and often transiently reversed when statins are acutely discontinued. Acute removal of pleiotropic effects and rebound vascular dysfunction may be more important in an acute coronary event, where inflammation promotes rupture of atherosclerotic plaques and inflammatory and prothrombosis markers are present in high concentration, than in stable chronic vascular disease. In the absence of data from randomized controlled trials, current information suggests that

  10. Forced ethanol ingestion by Wistar rats from a juvenile age increased voluntary alcohol consumption in adulthood, with the involvement of orexin-A.

    PubMed

    Mendoza-Ruiz, Luis-Gabriel; Vázquez-León, Priscila; Martínez-Mota, Lucía; Juan, Eduardo Ramírez San; Miranda-Páez, Abraham

    2018-08-01

    Human adolescents who drink alcohol are more likely to become alcoholics in adulthood. Alcohol administration (intraperitoneally) or drinking (in a 2-bottle free choice paradigm) during the juvenile/adolescent age of rats promotes voluntary alcohol consumption in adulthood. On the other hand, there is growing evidence that the orexinergic system plays a role in several rewarded behaviors, including alcohol ingestion. Since it is unknown what effect is exerted in adulthood by forced oral ethanol intake and/or administration of orexin-A (OX-A) in juvenile rats, the present study aimed to evaluate this question. A group of male Wistar rats was forced to drink ethanol (10% v/v) as the only liquid in the diet from weaning (postnatal day 21) to postnatal day 67 (46 days), followed by a forced withdrawal period. An age-matched group was raised drinking tap water (control). OX-A or its vehicle was microinjected intracerebroventricularly (i.c.v.) (1 nmol/0.6 μL) to explore its effect as well. Locomotor activity and voluntary ethanol consumption were later assessed in all groups. The rats forced to consume ethanol early in life showed an elevated level of ambulation and alcohol ingestion in adulthood. A single injection of OX-A increased locomotor activity and acute ethanol intake in rats with or without prior exposure to alcohol at the juvenile stage. In conclusion, forced ethanol consumption in juvenile rats led to increased voluntary alcohol drinking behavior during adulthood, an effect likely facilitated by OX-A. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Taste responses to monosodium glutamate after alcohol exposure.

    PubMed

    Wrobel, Elzbieta; Skrok-Wolska, Dominika; Ziolkowski, Marcin; Korkosz, Agnieszka; Habrat, Boguslaw; Woronowicz, Bohdan; Kukwa, Andrzej; Kostowski, Wojciech; Bienkowski, Przemyslaw; Scinska, Anna

    2005-01-01

    The aim of the present study was to evaluate the effects of acute and chronic exposure to alcohol on taste responses to a prototypic umami substance, monosodium glutamate (MSG). The rated intensity and pleasantness of MSG taste (0.03-10.0%) was compared in chronic male alcoholics (n = 35) and control subjects (n = 25). In a separate experiment, the effects of acute exposure of the oral mucosa to ethanol rinse (0.5-4.0%) on MSG taste (0.3-3.0%) were studied in 10 social drinkers. The alcoholic and control group did not differ in terms of the rated intensity and pleasantness of MSG taste. Electrogustometric thresholds were significantly (P < 0.01) higher, i.e. worse, in the alcohol-dependent subjects. The difference remained significant after controlling for between-group differences in cigarette smoking and coffee drinking. Rinsing with ethanol did not alter either intensity or pleasantness of MSG taste in social drinkers. The present results suggest that: (i) neither acute nor chronic alcohol exposure modifies taste responses to MSG; (ii) alcohol dependence may be associated with deficit in threshold taste reactivity, as assessed by electrogustometry.

  12. Effects of caffeine on alcohol consumption and nicotine self-administration in rats.

    PubMed

    Rezvani, Amir H; Sexton, Hannah G; Johnson, Joshua; Wells, Cori; Gordon, Karen; Levin, Edward D

    2013-09-01

    Caffeine, alcohol, and nicotine are 3 of the most widespread self-administered psychoactive substances, which are known to be extensively co-administered. However, little is known about the degree to which they may mutually potentiate each other's consumption. In the current set of studies, we examined in rats the effect of caffeine administration on alcohol drinking and intravenous (i.v.) self-administration of nicotine. In male alcohol-preferring (P) rats, caffeine (5, 10, and 20 mg/kg) or the saline vehicle was administered acutely either by subcutaneous (S.C.) injection or orally (PO) by gavage. In a chronic study, the effect of PO caffeine (5 and 20 mg/kg) on alcohol intake over a 10-day period was tested. In another experiment, the effect of acute PO administration of caffeine (20 mg/kg) or saline on saccharin intake (0.2% solution) was determined in P rats. Effects of 20 mg/kg caffeine on motor activity were also determined in P rats. Finally, the effects of acute PO caffeine administration on nicotine self-administration in Sprague-Dawley rats were also determined. Both routes of administration of caffeine, S.C. and PO, caused a significant dose-related decrease in alcohol intake and preference during free access to alcohol and after 4-day deprivation of alcohol. However, the low dose of 5 mg/kg caffeine increased alcohol intake. Acute PO caffeine also reduced saccharin intake. Acute systemic administration of 20 mg/kg caffeine did not exert a significant effect on motor activity. In Sprague-Dawley rats trained to self-administer i.v. nicotine, acute PO administration of caffeine significantly increased self-administration of nicotine in a dose-related manner. These results suggest that adenosine receptor systems may play a role in both alcohol and nicotine intake and deserve further study regarding these addictions. Copyright © 2013 by the Research Society on Alcoholism.

  13. Gender differences in self-reported withdrawal symptoms and reducing or quitting smoking three years later: A prospective, longitudinal examination of U.S. adults

    PubMed Central

    Weinberger, Andrea H.; Platt, Jonathan; Shuter, Jonathan; Goodwin, Renee D.

    2016-01-01

    Background Little is known about gender differences in withdrawal symptoms among smokers in the community. This study used longitudinal epidemiologic data to examine gender differences in current smokers’ report of withdrawal symptoms during past quit attempts and the relationship between withdrawal symptoms and the odds of reducing or quitting smoking three years later. Methods Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 1, 2001–2001, n=43,093; Wave 2, 2004–2005, n=34,653). Analyses were conducted on respondents who reported current daily cigarette smoking at Wave 1 (n=6,911). Withdrawal symptoms during past quit attempts were assessed at Wave 1. Current smoking status was assessed at Wave 2. Results Wave 1 current smoking women, compared to men, were more likely to endorse any withdrawal symptoms, withdrawal-related discomfort, and withdrawal-related relapse (ps<0.0001). Women endorsed a greater number of withdrawal symptoms than men (M=2.37, SE=0.05 versus M=1.78, SE=0.04; p<0.0001). The odds of reducing and quitting smoking were significantly lower for respondents who reported any Wave 1 withdrawal symptoms, withdrawal-related discomfort, and withdrawal-related relapse. These relationships did not differ for women versus men. Among men, the odds of reducing smoking at Wave 2 decreased significantly with each cumulative withdrawal symptom compared to women (β interaction= 0.87; p=0.01). Conclusions Women were more likely to report withdrawal while the relationship between withdrawal symptoms and decreased likelihood of reducing smoking was stronger in men. Identifying gender differences in withdrawal can help develop strategies to help reduce withdrawal for both men and women. PMID:27350655

  14. Self-reported alcohol intake and risk of acute exacerbations of chronic obstructive pulmonary disease: a prospective cohort study.

    PubMed

    Wetherbee, Erin E; Niewoehner, Dennis E; Sisson, Joseph H; Lindberg, Sarah M; Connett, John E; Kunisaki, Ken M

    2015-01-01

    To evaluate the relationship between alcohol consumption and the risk of acute exacerbation of COPD (AECOPD). We conducted a secondary analysis of data previously collected in a large, multicenter trial of daily azithromycin in COPD. To analyze the relationship between amount of baseline self-reported alcohol consumption in the past 12 months and subsequent AECOPD, we categorized the subjects as minimal (<1 drink/month), light-to-moderate (1-60 drinks/month), or heavy alcohol users (>60 drinks/month). The primary outcome was time to first AECOPD and the secondary outcome was AECOPD rate during the 1-year study period. Of the 1,142 enrolled participants, 1,082 completed baseline alcohol questionnaires and were included in this analysis. Six hundred and forty-five participants reported minimal alcohol intake, 363 reported light-to-moderate intake, and 74 reported heavy intake. There were no statistically significant differences in median time to first AECOPD among minimal (195 days), light-to-moderate (241 days), and heavy drinkers (288 days) (P=0.11). The mean crude rate of AECOPD did not significantly differ between minimal (1.62 events per year) and light-to-moderate (1.44 events per year) (P=0.095), or heavy drinkers (1.68 events per year) (P=0.796). There were no significant differences in hazard ratios for AECOPD after adjustment for multiple covariates. Among persons with COPD at high risk of exacerbation, we found no significant relationship between self-reported baseline alcohol intake and subsequent exacerbations. The number of patients reporting heavy alcohol intake was small and further study is needed to determine the effect of heavy alcohol intake on AECOPD risk.

  15. Alcoholism: genes and mechanisms.

    PubMed

    Oroszi, Gabor; Goldman, David

    2004-12-01

    Alcoholism is a chronic relapsing/remitting disease that is frequently unrecognized and untreated, in part because of the partial efficacy of treatment. Only approximately one-third of patients remain abstinent and one-third have fully relapsed 1 year after withdrawal from alcohol, with treated patients doing substantially better than untreated [1]. The partial effectiveness of strategies for prevention and treatment, and variation in clinical course and side effects, represent a challenge and an opportunity to better understand the neurobiology of addiction. The strong heritability of alcoholism suggests the existence of inherited functional variants of genes that alter the metabolism of alcohol and variants of other genes that alter the neurobiologies of reward, executive cognitive function, anxiety/dysphoria, and neuronal plasticity. Each of these neurobiologies has been identified as a critical domain in the addictions. Functional alleles that alter alcoholism-related intermediate phenotypes include common alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 variants that cause the aversive flushing reaction; catechol-O-methyltransferase (COMT) Val158Met leading to differences in three aspects of neurobiology: executive cognitive function, stress/anxiety response, and opioid function; opioid receptor micro1 (OPRM1) Asn40Asp, which may serve as a gatekeeper molecule in the action of naltrexone, a drug used in alcoholism treatment; and HTTLPR, which alters serotonin transporter function and appears to affect stress response and anxiety/dysphoria, which are factors relevant to initial vulnerability, the process of addiction, and relapse.

  16. Daily marijuana users with past alcohol problems increase alcohol consumption during marijuana abstinence.

    PubMed

    Peters, Erica N; Hughes, John R

    2010-01-15

    Drug abuse treatment programs typically recommend complete abstinence because of a fear that clients who stop use of one drug will substitute another. A within-subjects study investigated whether consumption of alcohol and other substances changes during marijuana abstinence. Twenty-eight daily marijuana users who were not trying to stop or reduce their marijuana consumption completed an 8-day baseline period in which they used marijuana and other drugs as usual, a 13-day marijuana abstinence period, and a 7-day return-to-baseline period. Participants provided self-report of substance use daily and submitted urine samples twice weekly to verify marijuana abstinence. A diagnosis of past alcohol abuse or dependence significantly moderated the alcohol increase from baseline to marijuana abstinence (p<0.01), such that individuals with this diagnosis significantly increased alcohol use (52% increase) but those without this history did not (3% increase). Increases in marijuana withdrawal discomfort scores and alcohol craving scores from baseline to marijuana abstinence significantly and positively correlated with increases in alcohol use. Increases in cigarettes, caffeine, and non-marijuana illicit drugs did not occur. This study provides empirical validation of drug substitution in a subgroup of daily marijuana users, but results need to be replicated in individuals who seek treatment for marijuana problems. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  17. The effect of nimodipine on memory impairment during spontaneous morphine withdrawal in mice: Corticosterone interaction.

    PubMed

    Vaseghi, Golnaz; Rabbani, Mohammed; Hajhashemi, Valiollah

    2012-11-15

    Effects of the nimodipine, L-type calcium channel antagonist, has been studied on memory loss caused by spontaneous morphine withdrawal in mice. Mice were made dependent by increasing doses of morphine over three days. Memory was evaluated using object recognition task, which is based on tendency of rodents to exploration of new objects. The test was comprised of three sections: 15 min habitation, 12 min first trial and 5 min test trial. Recognition index was evaluated 4h after the last dose of morphine. Nimodipine was administrated either in chronic form (1, 5 and 10mg/kg) with daily doses of morphine or it was given as a single injection (5 and 10mg/kg) on the last day. Nimodipine in both treatment forms prevented the memory impairment following spontaneous morphine withdrawal. Corticosterone concentration was increased in brain and blood of mice during abstinence phase and pretreatment with nimodipine prevented the increase in brain and blood corticosterone concentration. The results show that blockade of L-type calcium channels improves memory deficits caused by morphine withdrawal. This indicates that some kind of treatments, such as nimodipine, administrated over the acute withdrawal phase, can prevent memory deficit during withdrawal. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. The association between social anhedonia, withdrawal and psychotic experiences in general and high-risk populations.

    PubMed

    Velthorst, Eva; Meijer, Carin

    2012-07-01

    Social anhedonia (SA) and withdrawal are clinically relevant phenomena in schizophrenia. To examine the nature of the overlap between SA, withdrawal and positive symptoms, we investigated whether the co-occurrence of these phenotypes is more prominent in siblings of patients with a psychotic disorder compared to healthy controls, and if this association is independent of the amount of distress caused by psychotic experiences (PEs). Data were derived from 646 unaffected siblings and 326 healthy controls who were included in the Dutch Genetic Risk and Outcome in Psychosis (GROUP) study. PEs were assessed with the Community Assessment of Psychic Experiences and the Structured Interview for Schizotypy-Revised was used to examine social anhedonia and withdrawal. Our results show relatively small but significant cross-sectional associations between SA, withdrawal and PEs in unaffected siblings and none in the control group, irrespective of the level of distress caused by PEs. The findings of the present study suggest that the overlap between SA, withdrawal and psychotic symptoms often reported in schizophrenia patients, may at least partly reflect a shared genetic vulnerability, instead of merely being either a state marker of - or reaction to - acute psychotic symptoms. Copyright © 2012. Published by Elsevier B.V.

  19. Withdrawal: Expanding a Key Addiction Construct.

    PubMed

    Piper, Megan E

    2015-12-01

    Withdrawal is an essential component of classical addiction theory; it is a vital manifestation of dependence and motivates relapse. However, the traditional conceptualization of withdrawal as a cohesive collection of symptoms that emerge during drug deprivation and decline with either the passage of time or reinstatement of drug use, may be inadequate to explain scientific findings or fit with modern theories of addiction. This article expands the current understanding of tobacco withdrawal by examining: (1) withdrawal variability; (2) underlying causes of withdrawal variability, including biological and person factors, environmental influences, and the influence of highly routinized behavioral patterns; (3) new withdrawal symptoms that allow for enhanced characterization of the withdrawal experience; and (4) withdrawal-related cognitive processes. These topics provide guidance regarding the optimal assessment of withdrawal and illustrate the potential impact modern withdrawal conceptualization and assessment could have on identifying treatment targets. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Preventing the Consequences of Alcohol Abuse: Identification of Soldiers at High Risk for Fatal and Serious Injuries

    DTIC Science & Technology

    2005-07-01

    Drug/Alcohol Combo: 1980-1985 1986-1988 303.1 - Alcohol dependence with drug abuse 303.07 - Alcohol dependence syndrome - acute alcohol intoxication...with single drug use 303.10 - Alcohol dependence with drug abuse, unspecified 303.08 - Alcohol dependence syndrome - acute alcohol intoxication, with...multiple drug use 303.11 - Alcohol dependence with drug abuse, 303.97 - Alcohol dependence syndrome - other and continuous/habitual unspecified alcohol