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  1. A comparison of motivations for use among users of crack cocaine and cocaine powder in a sample of simultaneous cocaine and alcohol users.

    PubMed

    Martin, Gina; Macdonald, Scott; Pakula, Basia; Roth, Eric A

    2014-03-01

    This study examined the motivations for using cocaine and alcohol comparing those who primarily smoked crack and those who primarily used cocaine powder when using simultaneously with alcohol. Motivations examined included: 1) to cope with a negative affect, 2) enhancement, 3) to be social and 4) to conform. The research design was a cross-sectional study in which clients in treatment for cocaine and alcohol problems completed a self-administered questionnaire about their substance use. Among those who primarily smoked crack or snorted cocaine when also using alcohol (n=153), there were 93 participants who reported primarily snorting cocaine and 60 participants who primarily reported smoking crack. Bivariate analyses found that those who primarily smoked crack reported lower social motivations to use alcohol and cocaine. When adjusting for other covariates in a multivariate analysis, social motivation was still significantly different between groups. Additionally, those who primarily smoked crack were more likely to be older, report higher cocaine dependence severity, be unemployed and were less likely to have completed some post-secondary education, than those who primarily snorted cocaine. No differences were found in enhancement, coping or conformity motivations between the two groups. These results suggest that simultaneous cocaine and alcohol use may have social importance to those who primarily snort cocaine, but that this importance is less evident to those who smoke crack. Consequently, future studies examining motivations for simultaneous cocaine and alcohol use should distinguish between different routes of cocaine administration. PMID:24290877

  2. Alcohol and cocaine. Clinical and pharmacological interactions.

    PubMed

    Gorelick, D A

    1992-01-01

    Both clinical experience and epidemiological studies in community and specialized (e.g., treatment) populations indicate that the prevalence of co-use of alcohol and cocaine, and the comorbidity of alcoholism and cocaine addiction, are greater than would be expected from the chance occurrence of two independent conditions. Alcohol and cocaine have pharmacokinetic and pharmacodynamic interactions that may account for some of this co-use. While their reinforcing properties have neuropharmacological and behavioral differences, a unified theory of reinforcement by alcohol and cocaine has been proposed, involving dopamine activity in the ventral tegmental area-nucleus accumbens circuit. Regardless of their pharmacology, the prevalent co-use of alcohol and cocaine has important implications for drug abuse treatment and indicates the need for future research on this topic.

  3. Cocaine and alcohol interactions in the rat: contribution of cocaine metabolites to the pharmacological effects.

    PubMed

    Pan, W J; Hedaya, M A

    1999-04-01

    The pharmacokinetics and pharmacodynamics of cocaine and its three metabolites, benzoylecgonine, norcocaine, and cocaethylene, were investigated in awake, freely moving rats. This work was performed to examine the effect of alcohol coadministration on the metabolic profile of cocaine and to determine the contribution of cocaine metabolites to the pharmacological responses observed after cocaine administration. The plasma and brain extracellular fluid concentration-time profiles were characterized after intravenous (iv) administration of cocaine and the three metabolites in a crossover experimental design. The neurochemical response, measured as the change in dopamine concentration in the nucleus accumbens, and the cardiovascular responses, measured as the change in the mean arterial blood pressure, heart rate, and QRS interval, were monitored simultaneously. Cocaethylene had the highest brain-to-plasma distribution ratio, followed by cocaine, norcocaine, and benzoylecgonine. The estimated total body clearances for cocaine, benzoylecgonine, norcocaine, and cocaethylene were 140 +/- 19, 14.7 +/- 1.2, 130 +/- 19, and 111 +/- 16 mL/min/kg, respectively. Alcohol coadministration increased the formation of norcocaine, decreased the formation of benzoylecgonine, and resulted in the formation of the pharmacologically active metabolite cocaethylene. When cocaine was administered with alcohol, 12.9 +/- 3.1% to 15.3 +/- 2.9% of the cocaine dose was converted to cocaethylene. Benzoylecgonine did not have any central nervous system or cardiovascular activities after iv administration. Compared with cocaine, norcocaine and cocaethylene had more potent and prolonged effects on the neurochemical, heart rate, and QRS interval responses, and were equipotent in increasing the mean arterial blood pressure. These results indicate that changes in the cocaine metabolic profile and the formation of the pharmacologically active metabolite cocaethylene are, at least partially, responsible

  4. Alcohol administration increases cocaine craving but not cocaine cue attentional bias

    PubMed Central

    Marks, Katherine R.; Pike, Erika; Stoops, William W.; Rush, Craig R.

    2015-01-01

    Background Alcohol consumption is a known antecedent to cocaine relapse. Through associative conditioning, it is hypothesized that alcohol increases incentive motivation for cocaine and thus the salience of cocaine-related cues, which are important in maintaining drug-taking behavior. Cocaine-using individuals display a robust cocaine cue attentional bias as measured by fixation time during the visual probe task. The purpose of the present study was to evaluate the influence of alcohol administration on cocaine cue attentional bias using eye-tracking technology to directly measure attentional allocation. Methods Twenty current cocaine users completed a double-blind, placebo-controlled, within-subjects study that tested the effect of three doses of alcohol (0.00, 0.325, 0.65 g/kg alcohol) on cocaine cue attentional bias using the visual probe task with eye-tracking technology. The participant-rated and physiological effects of alcohol were also assessed. Results Participants displayed a robust cocaine cue attentional bias following both placebo and alcohol administration as measured by fixation time, but not response time. Alcohol administration did not influence cocaine cue attentional bias, but increased craving for cocaine in a dose dependent manner. Alcohol produced prototypic psychomotor and participant-rated effects. Conclusions Alcohol administration increases cocaine craving but not cocaine cue attentional bias. Alcohol-induced cocaine craving suggests that alcohol increases incentive motivation for cocaine but not the salience of cocaine-related cues. PMID:26331880

  5. Cognitive Predictors of Children's Attitudes toward Alcohol and Cocaine.

    ERIC Educational Resources Information Center

    Bridges, Lisa J.; Sigelman, Carol K.; Brewster, Albert B.; Leach, Diane B.; Mack, Keisha L.; Rinehart, Cheryl S.; Sorongon, Alberto G.

    2003-01-01

    Examines age differences in, and associations among, children's attitudes and intentions regarding alcohol and cocaine use and possible cognitive underpinnings of such orientations. Attitudes and intentions were negative and became less negative with age for alcohol, but more negative with age for cocaine. The cognitive predictors contributed to…

  6. Differences between Alcoholics and Cocaine Addicts Seeking Treatment.

    PubMed

    López-Goñi, José J; Fernández-Montalvo, Javier; Arteaga, Alfonso

    2015-03-03

    This study explored the characteristics of a representative sample of patients who were addicted to either alcohol or cocaine, comparing the profiles of both types of drug users. A sample of 234 addicted patients (109 alcoholics and 125 cocaine addicts) who sought outpatient treatment in a Spanish clinical centre was assessed. Data on socio-demographic, consumption, psychopathological and maladjustment characteristics were collected using the European Addiction Severity Index (EuropASI), the Symptom Checklist-90-Revised (SCL-90-R) and the Millon Clinical Multiaxial Inventory (MCMI-II). Demographically, differences were observed with regard to age (alcoholics were older than cocaine addicts; t = 12.2, p = .001), employment (the alcoholic group had more labor problems; χ 2 = 6.2, p = .045) and family consequences (worse in alcoholics; t = 2.3, p = .025). The EuropASI results showed statistically significant differences in addiction severity, with alcoholics showing a greater severity than cocaine addicts. In terms of psychopathology, alcoholics presented more associated symptomatology than cocaine addicts. According to these results, patients with alcohol dependence have a different profile from patients with cocaine dependence, resulting in different repercussions for important areas of their lives. These differences should be taken into account when standard treatments for addiction are implemented.

  7. Cocaine

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Cocaine KidsHealth > For Teens > Cocaine Print A A A ... How Can Someone Quit? Avoiding Cocaine What Is Cocaine? Cocaine is a powerful and highly addictive drug ...

  8. Cocaine

    MedlinePlus

    ... DEA Press Room » Multi-Media Library » Image Gallery » Cocaine COCAINE To Save Images: First click on the thumbnail ... your Save in directory and then click Save. Cocaine Crack Cocaine RESOURCE CENTER Controlled Substances Act DEA ...

  9. Cocaine

    MedlinePlus

    ... Search Share Print Home » Drugs of Abuse » Cocaine Cocaine Email Facebook Twitter Brief Description Cocaine is a ... NIDA for Teens: Stimulants NIDA Therapy Manuals for Cocaine Addiction (Archives): Manual 1: A Cognitive-Behavioral Approach: ...

  10. Cocaine Influences Alcohol-Seeking Behavior and Relapse Drinking in Alcohol-Preferring (P) Rats

    PubMed Central

    Hauser, Sheketha R.; Wilden, Jessica A.; Deehan, Gerald A.; McBride, William J.; Rodd, Zachary A.

    2014-01-01

    Background The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for one drug can be enhanced by exposure to another drug of abuse. The objective of the current study was to assess the time-course effects of acute cocaine administration on alcohol seeking and relapse. Methods Alcohol-Preferring (P) rats were allowed to self-administer 15% ethanol (EtOH) and water. EtOH-seeking was assessed through use of the Pavlovian Spontaneous Recovery (PSR) model, while relapse EtOH drinking was assessed through use of the alcohol deprivation effect. Results Cocaine (0, 1 or 10 mg/kg), injected immediately, 30 min, or 4 hr prior to the 1st PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hr prior to the relapse session markedly enhanced EtOH responding compared to saline. Conclusion The enhanced expression of EtOH-seeking and relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate) and priming of relapse/seeking (4 hour delay). PMID:25346508

  11. Cocaine.

    ERIC Educational Resources Information Center

    Piazza, Nick J.; Yeager, Rebecca D.

    Cocaine was first used by Europeans in the nineteenth century when extract from the coca leaf was combined with various beverages. Cocaine comes as a white crystalline powder. However, a product called crack cocaine may come as an opaque crystal similar in size and shape to rock salt. A third form of cocaine is known as coca paste, which is an…

  12. A double-blind, placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence

    PubMed Central

    Kampman, Kyle M.; Pettinati, Helen M.; Lynch, Kevin G.; Spratt, Kelly; Wierzbicki, Michael R.; O’Brien, Charles P.

    2013-01-01

    BACKGROUND Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs. METHODS The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings. RESULTS Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate. DISCUSSION Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence. PMID:23810644

  13. Cocaine

    MedlinePlus

    Cocaine is a white powder. It can be snorted up the nose or mixed with water and injected with a needle. Cocaine can also be made into small white rocks, ... Crack is smoked in a small glass pipe. Cocaine speeds up your whole body. You may feel ...

  14. Prenatal Exposure to Drugs/Alcohol: Characteristics and Educational Implications of Fetal Alcohol Syndrome and Cocaine/Polydrug Effects.

    ERIC Educational Resources Information Center

    Soby, Jeanette M.

    This book presents the characteristics of children affected by prenatal drug exposure, fetal alcohol syndrome, fetal alcohol effects, and fetal cocaine/polydrug effects. It outlines incidence, service needs, prevention, and identification. The medical literature on the physical, cognitive, and behavioral characteristics of this population is…

  15. Cocaine

    PubMed Central

    Agarwal, Ravindra; Wagner, Brent

    2015-01-01

    Cocaine abuse is commonly associated with myocardial ischemia, mesenteric ischemia, and cerebrovascular accidents. Renal infarction is an uncommon complication of cocaine abuse. Various mechanisms have been postulated for this cocaine-related injury. There are only 15 cases reported on cocaine-induced renal infarction. Among the cases with available data, very few cases had left kidney involvement. We report a case of a 65-year-old African American man with history of cocaine abuse who presented with left flank pain and had left renal infarction. PMID:26425633

  16. Executive Functioning in Preschool-Age Children Prenatally Exposed to Alcohol, Cocaine, and Marijuana

    PubMed Central

    Noland, Julia S.; Singer, Lynn T.; Arendt, Robert E.; Minnes, Sonia; Short, Elizabeth J.; Bearer, Cynthia F.

    2008-01-01

    Background Reports from clinical and experimental (animal) research converge on the suggestion that prenatal exposure to alcohol, cocaine, or marijuana undermines executive functioning (EF) and its neurological underpinnings. However, large, adequately controlled, prospective studies of alcohol and marijuana effects on EF have reported conflicting findings, and there have been no such studies of cocaine exposure. Methods EF was investigated in a cohort (n = 316) of 4-year-old children the majority of whose mothers had used varying combinations of cocaine, alcohol, and marijuana during pregnancy. With use of postpartum maternal report and biological assay, children were assigned to overlapping prenatal cocaine-exposed, alcohol-exposed, and marijuana-exposed groups and to complementary control groups. The postnatal environmental assessment included measures of maternal intellectual and psychosocial functioning, current drug or alcohol use, and home environment. Results The children in the alcohol-exposed group had worse tapping-inhibition performance than children in the non–alcohol-exposed group, and this effect persisted when potential confounding environmental variables, other drug variables, and concurrent verbal intelligence were controlled for. Conclusions Prenatal alcohol is predictive of decreased EF in early childhood that could not be attributed to environmental factors. The results are discussed in terms of the age and overall high-risk status of the children. PMID:12711927

  17. Prenatal Alcohol and Cocaine Exposure: Influences on Cognition, Speech, Language, and Hearing

    ERIC Educational Resources Information Center

    Cone-Wesson, B.

    2005-01-01

    This paper reviews research on the consequences of prenatal exposure to alcohol and cocaine on children's speech, language, hearing, and cognitive development. The review shows that cognitive impairment, learning disabilities, and behavioral disorders are the central nervous system manifestations of fetal alcohol syndrome (FAS), and cranio-facial…

  18. Gender Differences in Predictors of Treatment Attrition with High Dose Naltrexone in Cocaine and Alcohol Dependence

    PubMed Central

    Suh, Jesse J.; Pettinati, Helen M.; Kampman, Kyle M.; O’Brien, Charles P.

    2008-01-01

    Recently, we reported that naltrexone at 150mg/day significantly decreased cocaine and alcohol use for men, but not women with co-occurring cocaine and alcohol dependence. The present study is an exploratory investigation of predictors that explain the different gender response to naltrexone, with a particular focus on differential predictors of treatment attrition. No significant predictors were associated with treatment discontinuation in men. Women, however, were more likely to discontinue treatment when reporting severe pre-treatment psychiatric problems, or nausea while in treatment. Further research on the impact of pre-treatment and in-treatment gender differences with naltrexone is warranted. PMID:19034737

  19. Alcohol and cocaine co-consumption in two European cities assessed by wastewater analysis.

    PubMed

    Rodríguez-Álvarez, Tania; Racamonde, Inés; González-Mariño, Iria; Borsotti, Andrea; Rodil, Rosario; Rodríguez, Isaac; Zuccato, Ettore; Quintana, José Benito; Castiglioni, Sara

    2015-12-01

    The quantitative determination of urinary biomarkers in raw wastewater has emerged in recent years as a promising tool for estimating the consumption of illicit drugs, tobacco and alcohol in a population and for comparing local and temporal trends. In this study, a three-year monitoring campaign (2012-2014) was conducted to compare alcohol and cocaine use in two European cities (Santiago de Compostela, Spain, and Milan, Italy) by wastewater analysis. Ethyl sulphate and benzoylecgonine were used, respectively, as biomarkers of ethanol and cocaine consumption and cocaethylene as an indicator of co-consumption of both substances. Biomarkers were measured using liquid chromatography-tandem mass spectrometry and concentrations were converted to rates of consumption using specific correction factors. Results were statistically compared in terms of geographic and temporal tendencies. Alcohol intake was significantly higher in Santiago than in Milan (13.6L versus 5.1L ethanol/1000 people day, averages). Cocaine use was higher in Milan than in Santiago de Compostela (800 versus 632 mg/1000 people day, averages). A significant higher consumption of both alcohol and cocaine was observed during the weekends (~23-75% more than on weekdays) in both cities. In terms of years, slight changes were observed, but no clear trends as representative of the whole year could be identified because of the limited number of days sampled. Co-consumption was evaluated using the cocaethylene/benzoylecgonine ratio, which was higher during the weekend in both cities (58% in Santiago and 47% in Milan over the non-weekend day means), indicating a greater co-consumption when cocaine is used as a recreational drug. Wastewater-based epidemiology gave estimates of alcohol and cocaine use in agreement with previous wastewater studies and with recent European surveillance and prevalence data, and weekly profiles of use and preferential patterns of consumption could be plot. PMID:26196073

  20. Alcohol and cocaine co-consumption in two European cities assessed by wastewater analysis.

    PubMed

    Rodríguez-Álvarez, Tania; Racamonde, Inés; González-Mariño, Iria; Borsotti, Andrea; Rodil, Rosario; Rodríguez, Isaac; Zuccato, Ettore; Quintana, José Benito; Castiglioni, Sara

    2015-12-01

    The quantitative determination of urinary biomarkers in raw wastewater has emerged in recent years as a promising tool for estimating the consumption of illicit drugs, tobacco and alcohol in a population and for comparing local and temporal trends. In this study, a three-year monitoring campaign (2012-2014) was conducted to compare alcohol and cocaine use in two European cities (Santiago de Compostela, Spain, and Milan, Italy) by wastewater analysis. Ethyl sulphate and benzoylecgonine were used, respectively, as biomarkers of ethanol and cocaine consumption and cocaethylene as an indicator of co-consumption of both substances. Biomarkers were measured using liquid chromatography-tandem mass spectrometry and concentrations were converted to rates of consumption using specific correction factors. Results were statistically compared in terms of geographic and temporal tendencies. Alcohol intake was significantly higher in Santiago than in Milan (13.6L versus 5.1L ethanol/1000 people day, averages). Cocaine use was higher in Milan than in Santiago de Compostela (800 versus 632 mg/1000 people day, averages). A significant higher consumption of both alcohol and cocaine was observed during the weekends (~23-75% more than on weekdays) in both cities. In terms of years, slight changes were observed, but no clear trends as representative of the whole year could be identified because of the limited number of days sampled. Co-consumption was evaluated using the cocaethylene/benzoylecgonine ratio, which was higher during the weekend in both cities (58% in Santiago and 47% in Milan over the non-weekend day means), indicating a greater co-consumption when cocaine is used as a recreational drug. Wastewater-based epidemiology gave estimates of alcohol and cocaine use in agreement with previous wastewater studies and with recent European surveillance and prevalence data, and weekly profiles of use and preferential patterns of consumption could be plot.

  1. Cocaine

    MedlinePlus

    ... the neurotransmitter in the brain. It is this flood of dopamine that causes cocaine’s high. The drug ... Articles: Stimulants Research Report Series: Cocaine Statistics and Trends NIDA: DrugFacts: High School and Youth Trends Centers ...

  2. Is serum brain-derived neurotrophic factor related to craving for or use of alcohol, cocaine, or methamphetamine?

    PubMed Central

    Hilburn, Craig; Nejtek, Vicki A; Underwood, Wendy A; Singh, Meharvan; Patel, Gauravkumar; Gangwani, Pooja; Forster, Michael J

    2011-01-01

    Background Data suggests that brain-derived neurotropic factor (BDNF) plays a neuroadaptive role in addiction. Whether serum BDNF levels are different in alcohol or psychostimulants as a function of craving is unknown. Here, we examined craving and serum BDNF levels in persons with alcohol versus psychostimulant dependence. Our goals were to explore BDNF as an objective biomarker for 1) craving 2) abstinence, and 3) years of chronic substance use. Methods An exploratory, cross-sectional study was designed. Men and women between 20–65 years old with alcohol, cocaine, or methamphetamine dependence were eligible. A craving questionnaire was used to measure alcohol, cocaine and methamphetamine cravings. Serum levels of BDNF were measured using enzyme linked immunoassay. Analysis of variance, chi-square, and correlations were performed using a 95% confidence interval and a significance level of P < 0.05. Results We found a significant difference in the mean craving score among alcohol, cocaine and methamphetamine dependent subjects. There were no significant influences of race, gender, psychiatric disorder or psychotropic medication on serum BDNF levels. We found that among psychostimulant users BDNF levels were significantly higher in men than in women when the number of abstinent days was statistically controlled. Further, a significant correlation between serum BDNF levels and the number of abstinent days since last psychostimulant use was found. Conclusion These data suggest that BDNF may be a biomarker of abstinence in psychostimulant dependent subjects and inform clinicians about treatment initiatives. The results are interpreted with caution due to small sample size and lack of a control group. PMID:21792305

  3. Mediators of Telephone-Based Continuing Care for Alcohol and Cocaine Dependence

    ERIC Educational Resources Information Center

    Mensinger, Janell Lynn; Lynch, Kevin G.; Tenhave, Thomas R.; McKay, James R.

    2007-01-01

    A previous randomized trial with 224 alcohol and/or cocaine addicts who had completed an initial phase of treatment indicated that 12 weeks of telephone-based continuing care yielded higher abstinence rates over 24 months than did group counseling continuing care. The current study examined mediators of this treatment effect. Results suggested…

  4. Personality disorders among alcohol-dependent patients manifesting or not manifesting cocaine abuse: a comparative pilot study.

    PubMed

    Echeburúa, Enrique; De Medina, Ricardo Bravo; Aizpiri, Javier

    2009-01-01

    This study assessed personality disorders (PDs) in 158 alcohol-dependent outpatients (62 manifesting cocaine abuse and 96 without cocaine abuse) with the International Personality Disorders Examination interview between 2003 and 2006. Thirty-nine alcohol-dependent/cocaine abusers (62.9% of this group) and 51 only alcohol-dependent patients (53.1% of this group) manifested at least one PD. There were no statistically significant differences between groups in the overall prevalence rate of PDs. The most prevalent PDs, among the alcohol-dependent/cocaine abusers, were antisocial (21%), narcissistic (14.5%), and borderline (11.3%) PDs. The most frequently diagnosed PDs among the only alcohol-dependent patients were obsessive-compulsive (20.8%), paranoid (10.4%), and dependent (9.4%) PDs. There were significant differences between the groups. The study limitations are discussed.

  5. The role of the neurokinin-1 receptor in stress-induced reinstatement of alcohol and cocaine seeking.

    PubMed

    Schank, Jesse R; King, Courtney E; Sun, Hui; Cheng, Kejun; Rice, Kenner C; Heilig, Markus; Weinshenker, David; Schroeder, Jason P

    2014-04-01

    Neurokinin-1 receptors (NK1Rs) have been shown to mediate alcohol and opiate, but not cocaine reward in rodents. We recently reported that NK1R antagonism also blocks stress-induced reinstatement of alcohol seeking in rats, but it is presently unknown whether these antirelapse properties extend to other drug classes. Although some work has suggested that intracranial substance P (SP) infusion reinstates cocaine seeking following extinction, no studies have indicated a direct role for the NK1R in reinstatement of cocaine seeking. Here, we explored the effect of the NK1R antagonist L822429 on yohimbine-induced reinstatement of alcohol or cocaine seeking in Long-Evans rats. Consistent with our previous findings with footshock-induced reinstatement of alcohol seeking in Wistar rats, we found that L822429 attenuates yohimbine-induced reinstatement of alcohol seeking, but does not affect baseline alcohol self-administration. We observed a similar suppression of yohimbine-induced reinstatement of cocaine seeking by L822429, and found that Long-Evans rats exhibit greater sensitivity to NK1R antagonism than Wistar rats. Accordingly, Long-Evans rats exhibit differences in the expression of NK1Rs in some subcortical brain regions. Combined, our findings suggest that while NK1R antagonism differentially influences alcohol- and cocaine-related behavior, this receptor mediates stress-induced seeking of both drugs.

  6. Stress system changes associated with marijuana dependence may increase craving for alcohol and cocaine

    PubMed Central

    Fox, Helen C.; Tuit, Keri L.; Sinha, Rajita

    2013-01-01

    Objective To date, little research exists defining bio-behavioral adaptations associated with both marijuana abuse and risk of craving and relapse to other drugs of abuse during early abstinence. Method Fifty-nine treatment-seeking individuals dependent on alcohol and cocaine were recruited. Thirty of these individuals were also marijuana (MJ) dependent; 29 were not. Twenty-six socially drinking healthy controls were also recruited. All participants were exposed to three 5-min guided imagery conditions (stress, alcohol/cocaine cue and relaxing), presented randomly, one per day across three consecutive days. Measures of craving, anxiety, heart rate, blood pressure, plasma adrenocorticotrophic hormone and cortisol were collected at baseline and subsequent recovery time points. Results The MJ-dependent group showed increased basal anxiety ratings and cardiovascular output alongside enhanced alcohol craving and cocaine craving, and dampened cardiovascular response to stress and cue. They also demonstrated elevated cue-induced anxiety and stress-induced cortisol and adrenocorticotrophic hormone levels, which were not observed in the non-MJ-dependent group or controls. Cue-related alcohol craving and anxiety were both predictive of a shorter number of days to marijuana relapse following discharge from inpatient treatment. Conclusions Findings provide some support for drug cross-sensitization in terms of motivational processes associated with stress-related and cue-related craving and relapse. PMID:23280514

  7. Epigenetic modulation of brain gene networks for cocaine and alcohol abuse.

    PubMed

    Farris, Sean P; Harris, Robert A; Ponomarev, Igor

    2015-01-01

    Cocaine and alcohol are two substances of abuse that prominently affect the central nervous system (CNS). Repeated exposure to cocaine and alcohol leads to longstanding changes in gene expression, and subsequent functional CNS plasticity, throughout multiple brain regions. Epigenetic modifications of histones are one proposed mechanism guiding these enduring changes to the transcriptome. Characterizing the large number of available biological relationships as network models can reveal unexpected biochemical relationships. Clustering analysis of variation from whole-genome sequencing of gene expression (RNA-Seq) and histone H3 lysine 4 trimethylation (H3K4me3) events (ChIP-Seq) revealed the underlying structure of the transcriptional and epigenomic landscape within hippocampal postmortem brain tissue of drug abusers and control cases. Distinct sets of interrelated networks for cocaine and alcohol abuse were determined for each abusive substance. The network approach identified subsets of functionally related genes that are regulated in agreement with H3K4me3 changes, suggesting cause and effect relationships between this epigenetic mark and gene expression. Gene expression networks consisted of recognized substrates for addiction, such as the dopamine- and cAMP-regulated neuronal phosphoprotein PPP1R1B/DARPP-32 and the vesicular glutamate transporter SLC17A7/VGLUT1 as well as potentially novel molecular targets for substance abuse. Through a systems biology based approach our results illustrate the utility of integrating epigenetic and transcript expression to establish relevant biological networks in the human brain for addiction. Future work with laboratory models may clarify the functional relevance of these gene networks for cocaine and alcohol, and provide a framework for the development of medications for the treatment of addiction. PMID:26041984

  8. Epigenetic modulation of brain gene networks for cocaine and alcohol abuse

    PubMed Central

    Farris, Sean P.; Harris, Robert A.; Ponomarev, Igor

    2015-01-01

    Cocaine and alcohol are two substances of abuse that prominently affect the central nervous system (CNS). Repeated exposure to cocaine and alcohol leads to longstanding changes in gene expression, and subsequent functional CNS plasticity, throughout multiple brain regions. Epigenetic modifications of histones are one proposed mechanism guiding these enduring changes to the transcriptome. Characterizing the large number of available biological relationships as network models can reveal unexpected biochemical relationships. Clustering analysis of variation from whole-genome sequencing of gene expression (RNA-Seq) and histone H3 lysine 4 trimethylation (H3K4me3) events (ChIP-Seq) revealed the underlying structure of the transcriptional and epigenomic landscape within hippocampal postmortem brain tissue of drug abusers and control cases. Distinct sets of interrelated networks for cocaine and alcohol abuse were determined for each abusive substance. The network approach identified subsets of functionally related genes that are regulated in agreement with H3K4me3 changes, suggesting cause and effect relationships between this epigenetic mark and gene expression. Gene expression networks consisted of recognized substrates for addiction, such as the dopamine- and cAMP-regulated neuronal phosphoprotein PPP1R1B/DARPP-32 and the vesicular glutamate transporter SLC17A7/VGLUT1 as well as potentially novel molecular targets for substance abuse. Through a systems biology based approach our results illustrate the utility of integrating epigenetic and transcript expression to establish relevant biological networks in the human brain for addiction. Future work with laboratory models may clarify the functional relevance of these gene networks for cocaine and alcohol, and provide a framework for the development of medications for the treatment of addiction. PMID:26041984

  9. [Perceived norms among Honduran university students about peers and tobacco, alcohol, marijuana and cocaine use].

    PubMed

    Figueroa, Syntia Dinora Santos; Cunningham, John; Strike, Carol; Brands, Bruna; Wright, Maria da Gloria Miotto

    2009-01-01

    The purpose of this study was to assess the difference between perceived norms and peers' drug use among sophomore and junior university students (from the field of education) aged 18 to 24 years. The Social Norms Theory was used as the theoretical framework. In total, 286 students participated in the study, 67% of which reported having consumed alcohol at least once in a lifetime and 28% stated being daily users. Students perceived that 62% of their peers used tobacco and 63% used alcohol. The perceived norm for drug use was slightly higher in women than in men. In conclusion, there is an overestimation between the perceived norm and use of alcohol, tobacco, marijuana and cocaine.

  10. Multigenerational and transgenerational inheritance of drug exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine.

    PubMed

    Yohn, Nicole L; Bartolomei, Marisa S; Blendy, Julie A

    2015-07-01

    Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations. The focus of this review is to discuss these multigenerational and transgenerational phenotypes in the offspring of animals exposed to drugs of abuse. Specifically, changes found following the administration of alcohol, opioids, cocaine, marijuana, and nicotine will be discussed. In addition, epigenetic modifications to the genome following administration of these drugs will be detailed as well as their potential for transmission to the next generation.

  11. Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use: a comprehensive review.

    PubMed

    Angarita, Gustavo A; Emadi, Nazli; Hodges, Sarah; Morgan, Peter T

    2016-04-26

    Sleep abnormalities are associated with acute and chronic use of addictive substances. Although sleep complaints associated with use and abstinence from addictive substances are widely recognized, familiarity with the underlying sleep abnormalities is often lacking, despite evidence that these sleep abnormalities may be recalcitrant and impede good outcomes. Substantial research has now characterized the abnormalities associated with acute and chronic use of alcohol, cannabis, cocaine, and opiates. This review summarizes this research and discusses the clinical implications of sleep abnormalities in the treatment of substance use disorders.

  12. A Double Blind, Placebo-Controlled Trial that Combines Disulfiram and Naltrexone for Treating Co-Occurring Cocaine and Alcohol Dependence

    PubMed Central

    Pettinati, Helen; Kampman, Kyle M.; Lynch, Kevin G.; Xie, Hu; Dackis, Charles; Rabinowitz, Amanda R.; O’Brien, Charles P.

    2008-01-01

    BACKGROUND This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence. METHODS 208 patients were randomized to disulfiram (250mg/day), naltrexone (100mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol. RESULTS Few safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiram-naltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol. CONCLUSION There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients. PMID:18079068

  13. Social Behavior of Offspring Following Prenatal Cocaine Exposure in Rodents: A Comparison with Prenatal Alcohol

    PubMed Central

    Sobrian, Sonya K.; Holson, R. R.

    2011-01-01

    Clinical and experimental reports suggest that prenatal cocaine exposure (PCE) alters the offsprings’ social interactions with caregivers and conspecifics. Children exposed to prenatal cocaine show deficits in caregiver attachment and play behavior. In animal models, a developmental pattern of effects that range from deficits in play and social interaction during adolescence, to aggressive reactions during competition in adulthood is seen. This review will focus primarily on the effects of PCE on social behaviors involving conspecifics in animal models. Social relationships are critical to the developing organism; maternally directed interactions are necessary for initial survival. Juvenile rats deprived of play behavior, one of the earliest forms of non-mother directed social behaviors in rodents, show deficits in learning tasks and sexual competence. Social behavior is inherently complex. Because the emergence of appropriate social skills involves the interplay between various conceptual and biological facets of behavior and social information, it may be a particularly sensitive measure of prenatal insult. The social behavior surveyed include social interactions, play behavior/fighting, scent marking, and aggressive behavior in the offspring, as well as aspects of maternal behavior. The goal is to determine if there is a consensus of results in the literature with respect to PCE and social behaviors, and to discuss discrepant findings in terms of exposure models, the paradigms, and dependent variables, as well as housing conditions, and the sex and age of the offspring at testing. As there is increasing evidence that deficits in social behavior may be sequelae of developmental exposure alcohol, we compare changes in social behaviors reported for prenatal alcohol with those reported for prenatal cocaine. Shortcomings in the both literatures are identified and addressed in an effort to improve the translational value of future experimentation. PMID:22144967

  14. The rate ratio of injury and aggressive incident for alcohol alone, cocaine alone and simultaneous use before the event: A case-crossover study

    PubMed Central

    Zhao, Jinhui; Macdonald, Scott; Borges, Guilherme; Joordens, Chantele; Stockwell, Tim; Ye, Yu

    2015-01-01

    Objectives (i) To estimate the Rate Ratio (RR) of use of alcohol alone, cocaine alone, and both substances simultaneously on acute injury or an aggressive incident, (ii) To compare the RRs for simultaneous use within 3 or 6 hours of the event; and (iii) To compare the RRs of two measures of exposure, “hours of feeling effects” versus estimates based on self-reported quantity and frequency of use. Methods The study employed a case-crossover design with the frequency approach. Clients (N=616) in substance abuse treatment for alcohol or cocaine issues from 2009 to 2012 completed a self-administered questionnaire on their substance use within 3 and 6 hours before a recent injury or physically aggressive incident. Clients also reported detailed quantity and frequency information in relation to their typical substance use, as well as information on “feeling effects”. The RR of acute harms due to substance use was estimated using the Mantel-Haenszel estimator. Results In the 6-hour window before the event, use of cocaine alone, alcohol alone and simultaneous alcohol and cocaine use were each significantly (P <0.05) related to a recent injury and aggressive incident. Simultaneous use was not significantly greater than use of either drug alone. Estimates of RR based on simultaneous use for a 3-hour window before the event were consistently larger than those based on a 6-hour window, and comparisons were significant (P <0.05) for an aggressive incident but not an injury. With reference to the two measures of exposure, three of eight comparisons of RRs were significantly larger for feeling the effects of the substance in comparison to quantity and frequency of substance use. Conclusion These findings are consistent with increased likelihood of harms related to the acute effects of alcohol alone, cocaine alone or simultaneous use. The results are suggestive that the acute effects of these drugs may be better measured within a 3-hour time window than a 6-hour window

  15. Treatment-refractory substance use disorder: Focus on alcohol, opioids, and cocaine.

    PubMed

    Soyka, Michael; Mutschler, Jochen

    2016-10-01

    Substance use disorders are common, but only a small minority of patients receive adequate treatment. Although psychosocial therapies are effective, relapse is common. This review focusses on novel pharmacological and other treatments for patients with alcohol, opioid, or cocaine use disorders who do not respond to conventional treatments. Disulfiram, acamprosate, and the opioid antagonist naltrexone have been approved for the treatment of alcoholism. A novel, "as needed" approach is the use of the mu-opioid antagonist and partial kappa agonist nalmefene to reduce alcohol consumption. Other novel pharmacological approaches include the GABA-B receptor agonist baclofen, anticonvulsants such as topiramate and gabapentin, the partial nicotine receptor agonist varenicline, and other drugs. For opioid dependence, opioid agonist therapy with methadone or buprenorphine is the first-line treatment option. Other options include oral or depot naltrexone, morphine sulfate, depot or implant formulations, and heroin (diacetylmorphine) in treatment-refractory patients. To date, no pharmacological treatment has been approved for cocaine addiction; however, 3 potential pharmacological treatments are being studied, disulfiram, methylphenidate, and modafinil. Pharmacogenetic approaches may help to optimize treatment response in otherwise treatment-refractory patients and to identify which patients are more likely to respond to treatment, and neuromodulation techniques such as repeated transcranial magnetic stimulation and deep brain stimulation also may play a role in the treatment of substance use disorders. Although no magic bullet is in sight for treatment-refractory patients, some novel medications and brain stimulation techniques have the potential to enrich treatment options at least for some patients. PMID:26577297

  16. Prenatal coke: what's behind the smoke? Prenatal cocaine/alcohol exposure and school-age outcomes: the SCHOO-BE experience.

    PubMed

    Delaney-Black, V; Covington, C; Templin, T; Ager, J; Martier, S; Compton, S; Sokol, R

    1998-06-21

    Despite media reports and educators' concerns, little substantive data have been published to document or refute the emerging reports that children prenatally exposed to cocaine have serious behavioral problems in school. Recent pilot data from this institution have indeed demonstrated teacher-reported problem behaviors following prenatal cocaine exposure after controlling for the effects of prenatal alcohol use and cigarette exposure. Imperative in the study of prenatal exposure and child outcome is an acknowledgement of the influence of other control factors such as postnatal environment, secondary exposures, and parenting issues. We report preliminary evaluation from a large ongoing historical prospective study of prenatal cocaine exposure on school-age outcomes. The primary aim of this NIDA-funded study is to determine if a relationship exists between prenatal cocaine/alcohol exposures and school behavior and, if so, to determine if the relationship is characterized by a dose-response relationship. A secondary aim evaluates the relationship between prenatal cocaine/alcohol exposures and school achievement. Both relationships will be assessed in a black, urban sample of first grade students using multivariate statistical techniques for confounding as well as mediating and moderating prenatal and postnatal variables. A third aim is to evaluate the relationship between a general standardized classroom behavioral measure and a tool designed to tap the effects thought to be specific to prenatal cocaine exposure. This interdisciplinary research team can address these aims because of the existence of a unique, prospectively collected perinatal Database, funded in part by NIAAA and NICHD. The database includes repeated measures of cocaine, alcohol, and other substances for over 3,500 births since 1986. Information from this database is combined with information from the database of one of the largest public school systems in the nation. The final sample will be

  17. Polysomnographic measures of sleep in cocaine dependence and alcohol dependence: Implications for age‐related loss of slow wave, stage 3 sleep

    PubMed Central

    Bjurstrom, Martin F.; Olmstead, Richard

    2016-01-01

    Abstract Background and aims Sleep disturbance is a prominent complaint in cocaine and alcohol dependence. This controlled study evaluated differences of polysomnographic (PSG) sleep in cocaine‐ and alcohol‐dependent subjects, and examined whether substance dependence interacts with age to alter slow wave sleep and rapid eye movement (REM) sleep. Design Cross‐sectional comparison. Setting Los Angeles and San Diego, CA, USA. Participants Abstinent cocaine‐dependent subjects (n = 32), abstinent alcohol‐dependent subjects (n = 73) and controls (n = 108); mean age 40.3 years recruited 2005–12. Measurements PSG measures of sleep continuity and sleep architecture primary outcomes of Stage 3 sleep and REM sleep. Covariates included age, ethnicity, education, smoking, body mass index and depressive symptoms. Findings Compared with controls, both groups of substance dependent subjects showed loss of Stage 3 sleep (P < 0.001). A substance dependence × age interaction was found in which both cocaine‐ and alcohol‐dependent groups showed loss of Stage 3 sleep at an earlier age than controls (P < 0.05 for all), and cocaine‐dependent subjects showed loss of Stage 3 sleep at an earlier age than alcoholics (P < 0.05). Compared with controls, REM sleep was increased in both substance‐dependent groups (P < 0.001), and cocaine and alcohol dependence were associated with earlier age‐related increase in REM sleep (P < 0.05 for all). Conclusions Cocaine and alcohol dependence appear to be associated with marked disturbances of sleep architecture, including increased rapid eye movement sleep and accelerated age‐related loss of slow wave, Stage 3 sleep. PMID:26749502

  18. Multigenerational and Transgenerational Inheritance of Drug Exposure: The effects of alcohol, opiates, cocaine, marijuana, and nicotine

    PubMed Central

    Yohn, Nicole L.; Bartolomei, Marisa S.; Blendy, Julie A.

    2015-01-01

    Familial inheritance of drug abuse is composed of both genetic and environmental factors. Additionally, epigenetic transgenerational inheritance may provide a means by which parental drug use can influence several generations of offspring. Recent evidence suggests that parental drug exposure produces behavioral, biochemical, and neuroanatomical changes in future generations. The focus of this review is to discuss these multigenerational and transgenerational phenotypes in the offspring of animals exposed to drugs of abuse. Specifically, changes found following the administration of alcohol, opioids, cocaine, marijuana, and nicotine will be discussed. In addition, epigenetic modifications to the genome following administration of these drugs will be detailed as well as their potential for transmission to the next generation. PMID:25839742

  19. [Subtypes of cocaine addicts with and without associated problematic alcohol use: towards a neuropsychology of personality applied to clinical practice].

    PubMed

    Pedrero Pérez, Eduardo J; Ruiz Sánchez de León, José M

    2012-01-01

    It is important to know which personality factors are associated with addiction so to distinguish addicts that require specialized treatment from those who do not, and to identify those addicts who achieve abstinence from those who continue their substance use despite the negative consequences. Cloninger's model includes biological and psychosocial variables that can be characterized in neuropsychological terms. Two samples were analyzed: individuals who had begun cocaine addiction treatment (n=183) and a non-clinical population sample (n = 183), matched for sex, age and educational level. Alcohol abuse/dependence was monitored as an independent variable. Significant differences and large effect size were found between addicts and non-clinical population in Novelty Seeking and Self-Directedness, and to a lesser extent, in Harm Avoidance. These differences increase when problematic use of alcohol is added. According to the profile of traits, clusters of addicts were established and differences were obtained in variables such as functional/dysfunctional impulsivity, dysexecutive symptoms and perceived stress. Six clusters were identified, some of minor severity, the most severely problematic clusters being characterized by higher levels of dysfunctional impulsivity, more dysexecutive symptoms and higher levels of perceived stress. Self-Directedness seems to reflect the deficit of prefrontal systems in the regulation of behavior, as well as in emotion and impulse control. It is proposed that evaluation of the personality is more useful than the mere assessment of symptoms for classifying addicts, determining their needs and designing a therapeutic itinerary. PMID:23241716

  20. [Subtypes of cocaine addicts with and without associated problematic alcohol use: towards a neuropsychology of personality applied to clinical practice].

    PubMed

    Pedrero Pérez, Eduardo J; Ruiz Sánchez de León, José M

    2012-01-01

    It is important to know which personality factors are associated with addiction so to distinguish addicts that require specialized treatment from those who do not, and to identify those addicts who achieve abstinence from those who continue their substance use despite the negative consequences. Cloninger's model includes biological and psychosocial variables that can be characterized in neuropsychological terms. Two samples were analyzed: individuals who had begun cocaine addiction treatment (n=183) and a non-clinical population sample (n = 183), matched for sex, age and educational level. Alcohol abuse/dependence was monitored as an independent variable. Significant differences and large effect size were found between addicts and non-clinical population in Novelty Seeking and Self-Directedness, and to a lesser extent, in Harm Avoidance. These differences increase when problematic use of alcohol is added. According to the profile of traits, clusters of addicts were established and differences were obtained in variables such as functional/dysfunctional impulsivity, dysexecutive symptoms and perceived stress. Six clusters were identified, some of minor severity, the most severely problematic clusters being characterized by higher levels of dysfunctional impulsivity, more dysexecutive symptoms and higher levels of perceived stress. Self-Directedness seems to reflect the deficit of prefrontal systems in the regulation of behavior, as well as in emotion and impulse control. It is proposed that evaluation of the personality is more useful than the mere assessment of symptoms for classifying addicts, determining their needs and designing a therapeutic itinerary.

  1. Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol effects.

    PubMed

    Cittadini, Francesca; De Giovanni, Nadia; Alcalde, Mireia; Partemi, Sara; Carbone, Arnaldo; Campuzano, Oscar; Brugada, Ramon; Oliva, Antonio

    2015-01-01

    Cocaine and alcohol toxicity is well known, especially when simultaneously abused. These drugs perform both acute and chronic harmfulness, with significant cardiac events such as ventricular arrhythmias, tachycardia, systemic hypertension, acute myocardial infarction, ventricular hypertrophy, and acute coronary syndrome. The present report refers about a patient who died after a documented episode of psychomotor agitation followed by cardiac arrest. At the autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed and confirmed by postmortem molecular analysis revealing a mutation in the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of cocaine, and the death was attributed to cardiac arrhythmias. The detection of cocaine and cocaethylene in hair samples proved chronic simultaneous intake of cocaine and alcohol at least in the last month. The authors discuss the role of these drugs and genetic predisposition of the ARVC in causing the death of the patient. PMID:25399050

  2. Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity

    PubMed Central

    Larrimore, Katherine E; Barcus, Matthew; Kannan, Latha; Gao, Yang; Zhan, Chang-Guo; Brimijoin, Stephen; Mor, Tsafrir

    2012-01-01

    Cocaine addiction affects millions of people with disastrous personal and social consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have an over 80% chance of relapse. Yet there is no FDA-approved treatment to decrease the likelihood of relapse in rehabilitated addicts. Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking down naturally occurring (−)-cocaine before the drug can influence the reward centers of the brain or affect other areas of the body. This activity of wild-type (WT) BChE, however, is relatively low. This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against (−)-cocaine. Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources. Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus-assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof-of-principle that plants can express engineered BChE proteins with desired properties. PMID:23000451

  3. Plants as a source of butyrylcholinesterase variants designed for enhanced cocaine hydrolase activity.

    PubMed

    Larrimore, Katherine E; Barcus, Matthew; Kannan, Latha; Gao, Yang; Zhan, Chang-Guo; Brimijoin, Stephen; Mor, Tsafrir

    2013-03-25

    Cocaine addiction affects millions of people with disastrous personal and social consequences. Cocaine is one of the most reinforcing of all drugs of abuse, and even those who undergo rehabilitation and experience long periods of abstinence have more than 80% chance of relapse. Yet there is no FDA-approved treatment to decrease the likelihood of relapse in rehabilitated addicts. Recent studies, however, have demonstrated a promising potential treatment option with the help of the serum enzyme butyrylcholinesterase (BChE), which is capable of breaking down naturally occurring (-)-cocaine before the drug can influence the reward centers of the brain or affect other areas of the body. This activity of wild-type (WT) BChE, however, is relatively low. This prompted the design of variants of BChE which exhibit significantly improved catalytic activity against (-)-cocaine. Plants are a promising means to produce large amounts of these cocaine hydrolase variants of BChE, cheaply, safely with no concerns regarding human pathogens and functionally equivalent to enzymes derived from other sources. Here, in expressing cocaine-hydrolyzing mutants of BChE in Nicotiana benthamiana using the MagnICON virus-assisted transient expression system, and in reporting their initial biochemical analysis, we provide proof-of-principle that plants can express engineered BChE proteins with desired properties.

  4. Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine

    PubMed Central

    Hosseinnezhad, Alireza; Vijayakrishnan, Rajakrishnan; Farmer, Mary Jo S.

    2011-01-01

    Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL), thrombocytopenia (platelet count 74,000/UL), elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L) and elevated creatine phosphokinase (CPK 5885 U/L). Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause. PMID:24765297

  5. A factor analysis of global GABAergic gene expression in human brain identifies specificity in response to chronic alcohol and cocaine exposure.

    PubMed

    Enoch, Mary-Anne; Baghal, Basel; Yuan, Qiaoping; Goldman, David

    2013-01-01

    Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABAA gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from 'BrainSpan' was obtained across 16 brain regions from postmortem samples from nine adults. A factor analysis was performed on global expression of 21 GABAergic pathway genes. Factor specificity for response to chronic alcohol/cocaine exposure was subsequently determined from the analysis of RNA-Seq data from postmortem hippocampus of eight alcoholics, eight cocaine addicts and eight controls. Six gene expression factors were identified. Most genes loaded (≥0.5) onto one factor; six genes loaded onto two. The largest factor (0.30 variance) included the chromosome 5 gene cluster that encodes the most common GABAA receptor, α1β2γ2, and genes encoding the α3β3γ2 receptor. Genes within this factor were largely unresponsive to chronic alcohol/cocaine exposure. In contrast, the chromosome 4 gene cluster factor (0.14 variance) encoding the α2β1γ1 receptor was influenced by chronic alcohol/cocaine exposure. Two other factors (0.17 and 0.06 variance) showed expression changes in alcoholics/cocaine addicts; these factors included genes involved in GABA synthesis and synaptic transport. Finally there were two factors that included genes with exceptionally low (0.10 variance) and high (0.09 variance) expression in the cerebellum; the former factor was unaffected by alcohol/cocaine exposure. This study has shown that there appears to be specificity of GABAergic gene groups, defined by covariation in expression, for response to chronic alcohol/cocaine exposure. These findings might have implications for combating stress

  6. A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure

    PubMed Central

    Yuan, Qiaoping; Goldman, David

    2013-01-01

    Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABAA gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions from postmortem samples from nine adults. A factor analysis was performed on global expression of 21 GABAergic pathway genes. Factor specificity for response to chronic alcohol/cocaine exposure was subsequently determined from the analysis of RNA-Seq data from postmortem hippocampus of eight alcoholics, eight cocaine addicts and eight controls. Six gene expression factors were identified. Most genes loaded (≥0.5) onto one factor; six genes loaded onto two. The largest factor (0.30 variance) included the chromosome 5 gene cluster that encodes the most common GABAA receptor, α1β2γ2, and genes encoding the α3β3γ2 receptor. Genes within this factor were largely unresponsive to chronic alcohol/cocaine exposure. In contrast, the chromosome 4 gene cluster factor (0.14 variance) encoding the α2β1γ1 receptor was influenced by chronic alcohol/cocaine exposure. Two other factors (0.17 and 0.06 variance) showed expression changes in alcoholics/cocaine addicts; these factors included genes involved in GABA synthesis and synaptic transport. Finally there were two factors that included genes with exceptionally low (0.10 variance) and high (0.09 variance) expression in the cerebellum; the former factor was unaffected by alcohol/cocaine exposure. This study has shown that there appears to be specificity of GABAergic gene groups, defined by covariation in expression, for response to chronic alcohol/cocaine exposure. These findings might have implications for combating stress

  7. Design and synthesis of a fluorescent molecular imprinted polymer for use in an optical fibre-based cocaine sensor

    NASA Astrophysics Data System (ADS)

    Wren, Stephen P.; Piletsky, Sergey A.; Karim, Kal; Gascoine, Paul; Lacey, Richard; Sun, Tong; Grattan, Kenneth T. V.

    2014-05-01

    Previously, we have developed chemical sensors using fibre optic-based techniques for the detection of Cocaine, utilising molecularly imprinted polymers (MIPs) containing fluorescein moieties as the signalling groups. Here, we report the computational design of a fluorophore which was incorporated into a MIP for the generation of a novel sensor that offers improved sensitivity for Cocaine with a detection range of 1-100μM. High selectivity for Cocaine over a suite of known Cocaine interferants (25μM) was also demonstrated by measuring changes in the intensity of fluorescence signals received from the sensor.

  8. A Preliminary Examination of the Relationships between Posttraumatic Stress Symptoms and Crack/Cocaine, Heroin, and Alcohol Dependence

    PubMed Central

    Tull, Matthew T.; Gratz, Kim L.; Aklin, Will M.; Lejuez, C.W.

    2009-01-01

    High rates of co-occurrence between posttraumatic stress (PTS) and substance use disorders (SUDs) have led to the suggestion that substance use among individuals experiencing PTS symptoms might serve a self-medication function. However, research is still needed to provide a more comprehensive evaluation of the unique associations between PTS symptom clusters and substances (licit and illicit) with both anxiolytic/depressant and stimulant properties. Consequently, this study examined the relationship between severity of different PTS symptom clusters and heroin, crack/cocaine, and alcohol dependence among 48 treatment-seeking SUD patients with a history of traumatic exposure. No evidence was found for a relationship between PTS symptom clusters and crack/cocaine or alcohol dependence; however, results suggested a relationship between hyperarousal and avoidance (inversely-related) symptoms and heroin dependence. Results are discussed in terms of their implications for understanding motivations underlying the substance of choice among individuals with PTS symptoms, as well as the development of treatments for co-occurring PTS and SUDs. PMID:19767174

  9. The Angular Interval between the Direction of Progression and Body Orientation in Normal, Alcohol- and Cocaine Treated Fruit Flies

    PubMed Central

    Gakamsky, Anna; Oron, Efrat; Valente, Dan; Mitra, Partha P.; Segal, Daniel; Benjamini, Yoav; Golani, Ilan

    2013-01-01

    In this study we characterize the coordination between the direction a fruit-fly walks and the direction it faces, as well as offer a methodology for isolating and validating key variables with which we phenotype fly locomotor behavior. Our fundamental finding is that the angular interval between the direction a fly walks and the direction it faces is actively managed in intact animals and modulated in a patterned way with drugs. This interval is small in intact flies, larger with alcohol and much larger with cocaine. The dynamics of this interval generates six coordinative modes that flow smoothly into each other. Under alcohol and much more so under cocaine, straight path modes dwindle and modes involving rotation proliferate. To obtain these results we perform high content analysis of video-tracked open field locomotor behavior. Presently there is a gap between the quality of descriptions of insect behaviors that unfold in circumscribed situations, and descriptions that unfold in extended time and space. While the first describe the coordination between low-level kinematic variables, the second quantify cumulative measures and subjectively defined behavior patterns. Here we reduce this gap by phenotyping extended locomotor behavior in terms of the coordination between low-level kinematic variables, which we quantify, combining into a single field two disparate fields, that of high content phenotyping and that of locomotor coordination. This will allow the study of the genes/brain/locomotor coordination interface in genetically engineered and pharmacologically manipulated animal models of human diseases. PMID:24146845

  10. Expression of Glutamatergic Genes in Healthy Humans across 16 Brain Regions; Altered Expression in the Hippocampus after Chronic Exposure to Alcohol or Cocaine

    PubMed Central

    Enoch, Mary-Anne; Rosser, Alexandra A.; Zhou, Zhifeng; Mash, Deborah C.; Yuan, Qiaoping; Goldman, David

    2014-01-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions from nine control adults. We also generated RNA-Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic (AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up-regulated in both alcoholics and cocaine addicts (FDR corrected p = 0.008). Alcoholics showed up-regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 (GluR7) and GRM4 (mGluR4). Expression of both GRM3 (mGluR3) and GRIN2D (GluN2D) was up-regulated in alcoholics and down-regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up-regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit. PMID:25262781

  11. Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine.

    PubMed

    Enoch, M-A; Rosser, A A; Zhou, Z; Mash, D C; Yuan, Q; Goldman, D

    2014-11-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from 'BrainSpan' was obtained across 16 brain regions from nine control adults. We also generated RNA-Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic (AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up-regulated in both alcoholics and cocaine addicts (FDR corrected P = 0.008). Alcoholics showed up-regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 (GluR7) and GRM4 (mGluR4). Expression of both GRM3 (mGluR3) and GRIN2D (GluN2D) was up-regulated in alcoholics and down-regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up-regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit. PMID:25262781

  12. The effects of housing costs on polydrug abuse patterns: a comparison of heroin, cocaine, and alcohol abusers.

    PubMed

    Petry, N M

    2001-02-01

    This study evaluated how price of housing affects hypothetical purchasing decisions. Participants (26 heroin, 28 cocaine, and 15 alcohol abusers, and 25 controls) were exposed to 4 conditions in which they "purchased" drugs, food, housing, and entertainment. Whereas income remained constant, housing prices varied across conditions. Except for 23% of heroin abusers, participants purchased housing regardless of cost, so that income increased as housing cost decreased. Demand for food was income inelastic, whereas demand for entertainment was income elastic. Each group showed income elastic demand for their drug of choice. Hypothetical choices were reliable; drug choices were correlated with urinalysis results, and willingness to forgo housing in the simulation was correlated with time spent homeless in real life. This study shows that changes in housing prices may affect choices for drug and nondrug reinforcers. PMID:11519635

  13. Toward a Global View of Alcohol, Tobacco, Cannabis, and Cocaine Use: Findings from the WHO World Mental Health Surveys

    PubMed Central

    Degenhardt, Louisa; Chiu, Wai-Tat; Sampson, Nancy; Kessler, Ronald C; Anthony, James C; Angermeyer, Matthias; Bruffaerts, Ronny; de Girolamo, Giovanni; Gureje, Oye; Huang, Yueqin; Karam, Aimee; Kostyuchenko, Stanislav; Lepine, Jean Pierre; Mora, Maria Elena Medina; Neumark, Yehuda; Ormel, J. Hans; Pinto-Meza, Alejandra; Posada-Villa, José; Stein, Dan J; Takeshima, Tadashi; Wells, J. Elisabeth

    2008-01-01

    Background Alcohol, tobacco, and illegal drug use cause considerable morbidity and mortality, but good cross-national epidemiological data are limited. This paper describes such data from the first 17 countries participating in the World Health Organization's (WHO's) World Mental Health (WMH) Survey Initiative. Methods and Findings Household surveys with a combined sample size of 85,052 were carried out in the Americas (Colombia, Mexico, United States), Europe (Belgium, France, Germany, Italy, Netherlands, Spain, Ukraine), Middle East and Africa (Israel, Lebanon, Nigeria, South Africa), Asia (Japan, People's Republic of China), and Oceania (New Zealand). The WHO Composite International Diagnostic Interview (CIDI) was used to assess the prevalence and correlates of a wide variety of mental and substance disorders. This paper focuses on lifetime use and age of initiation of tobacco, alcohol, cannabis, and cocaine. Alcohol had been used by most in the Americas, Europe, Japan, and New Zealand, with smaller proportions in the Middle East, Africa, and China. Cannabis use in the US and New Zealand (both 42%) was far higher than in any other country. The US was also an outlier in cocaine use (16%). Males were more likely than females to have used drugs; and a sex–cohort interaction was observed, whereby not only were younger cohorts more likely to use all drugs, but the male–female gap was closing in more recent cohorts. The period of risk for drug initiation also appears to be lengthening longer into adulthood among more recent cohorts. Associations with sociodemographic variables were consistent across countries, as were the curves of incidence of lifetime use. Conclusions Globally, drug use is not distributed evenly and is not simply related to drug policy, since countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones. Sex differences were consistently documented, but are decreasing in more recent

  14. Women Inmate Substance Abusers’ Reactivity to Visual Alcohol, Cigarette, Marijuana, and Crack-Cocaine Cues: Approach and Avoidance as Separate Dimensions of Reactivity

    PubMed Central

    Schlauch, Robert C.; Breiner, Mary J.; Stasiewicz, Paul R.; Christensen, Rita L.; Lang, Alan R.

    2012-01-01

    Despite the growing recognition for multidimensional assessments of cue-elicited craving, few studies have attempted to measure multiple response domains associated with craving. The present study evaluated the Ambivalence Model of Craving (Breiner et al., 1999; Stritzke et al., 2007) using a unique cue reactivity methodology designed to capture both the desire to use (approach inclination) and desire to not consume (avoidance inclination) in a clinical sample of incarcerated female substance abusers. Participants were 155 incarcerated women who were participating in or waiting to begin participation in a nine-month drug treatment program. Results indicated that all four substance cue-types (alcohol, cigarette, marijuana, and crack cocaine) had good reliability and showed high specificity. Also, the validity of measuring approach and avoidance as separate dimensions was supported, as demonstrated by meaningful clinical distinctions between groups evincing different reactivity patterns and incremental prediction of avoidance inclinations on measures of stages of change readiness. Taken together, results continue to highlight the importance of measuring both approach and avoidance inclinations in the study of cue-elicited craving. PMID:23543075

  15. Neural Correlates of the Severity of Cocaine, Heroin, Alcohol, MDMA and Cannabis Use in Polysubstance Abusers: A Resting-PET Brain Metabolism Study

    PubMed Central

    Moreno-López, Laura; Stamatakis, Emmanuel A.; Fernández-Serrano, Maria José; Gómez-Río, Manuel; Rodríguez-Fernández, Antonio; Pérez-García, Miguel; Verdejo-García, Antonio

    2012-01-01

    Introduction Functional imaging studies of addiction following protracted abstinence have not been systematically conducted to look at the associations between severity of use of different drugs and brain dysfunction. Findings from such studies may be relevant to implement specific interventions for treatment. The aim of this study was to examine the association between resting-state regional brain metabolism (measured with 18F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and the severity of use of cocaine, heroin, alcohol, MDMA and cannabis in a sample of polysubstance users with prolonged abstinence from all drugs used. Methods Our sample consisted of 49 polysubstance users enrolled in residential treatment. We conducted correlation analyses between estimates of use of cocaine, heroin, alcohol, MDMA and cannabis and brain metabolism (BM) (using Statistical Parametric Mapping voxel-based (VB) whole-brain analyses). In all correlation analyses conducted for each of the drugs we controlled for the co-abuse of the other drugs used. Results The analysis showed significant negative correlations between severity of heroin, alcohol, MDMA and cannabis use and BM in the dorsolateral prefrontal cortex (DLPFC) and temporal cortex. Alcohol use was further associated with lower metabolism in frontal premotor cortex and putamen, and stimulants use with parietal cortex. Conclusions Duration of use of different drugs negatively correlated with overlapping regions in the DLPFC, whereas severity of cocaine, heroin and alcohol use selectively impact parietal, temporal, and frontal-premotor/basal ganglia regions respectively. The knowledge of these associations could be useful in the clinical practice since different brain alterations have been associated with different patterns of execution that may affect the rehabilitation of these patients. PMID:22768136

  16. Initiation of use of alcohol, cigarettes, marijuana, cocaine, and other substances in US birth cohorts since 1919.

    PubMed Central

    Johnson, R A; Gerstein, D R

    1998-01-01

    OBJECTIVES: This study examined recent trends in initiation of psychoactive drug use. METHODS: Data from the 1991 through 1993 National Household Surveys on Drug Abuse were used to compare the percentages of US cohorts born from 1919 through 1975 who began using drugs before the ages of 15, 21, and 35. RESULTS: Initiation of cigarette smoking by males peaked in the 1941-1945 cohort, then declined steadily. For females, early smoking initiation rose through the 1951-1955 cohort and then stabilized. Initiation of alcohol use was less common than smoking for pre1950 cohorts but increased steadily, approaching cigarette use for cohorts born in the early 1970s. Only 2% of teenagers born in 1930-1940 tried marijuana; half the teenagers born in 1956-1965 did so. The percentage initiating marijuana use declined in the 1980s, more so among young adults than among teenagers. The use of cocaine and other illicit drugs echoed the rise of marijuana use but peaked later and showed less evidence of subsequent decline. Sex differences declined over time for every drug. CONCLUSIONS: Cohorts born since World War II have had much higher rates of illicit drug use initiation, but trends have varied by drug type, possibly reflecting changes in relative prices. PMID:9584029

  17. Analysis of cocaine and two metabolites in dried blood spots by liquid chromatography with fluorescence detection: a novel test for cocaine and alcohol intake.

    PubMed

    Mercolini, Laura; Mandrioli, Roberto; Gerra, Gilberto; Raggi, Maria Augusta

    2010-11-12

    An original HPLC method coupled to spectrofluorimetric detection is presented for the simultaneous analysis in dried blood spots (DBS) of cocaine and two important metabolites, namely benzoylecgonine (its main metabolite) and cocaethylene (the active metabolite formed in the presence of ethanol). The chromatographic analysis was carried out on a C8 column, using a mobile phase containing phosphate buffer (pH 3.0)-acetonitrile (85:15, v/v). Native analyte fluorescence was monitored at 315 nm while exciting at 230 nm. A fast and feasible sample pre-treatment was implemented by solvent extraction, obtaining good extraction yields (>91%) and satisfactory precision values (RSD<4.8%). The method was successfully applied to DBS samples collected from some cocaine users, both with and without concomitant ethanol intake. The results were in good agreement with those obtained from plasma samples subjected to an original solid-phase extraction procedure on C8 cartridges. The method has demonstrated to be suitable for the monitoring of cocaine/ethanol use by means of DBS or plasma testing. Assays are in progress to apply this method on the street, for the control of subjects suspected of driving under the influence of psychotropic substances. PMID:20934184

  18. Metabolomics of cocaine: implications in toxicity.

    PubMed

    Dinis-Oliveira, Ricardo Jorge

    2015-01-01

    Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects.

  19. Metabolomics of cocaine: implications in toxicity.

    PubMed

    Dinis-Oliveira, Ricardo Jorge

    2015-01-01

    Cocaine is the most commonly used illicit drug among those seeking care in Emergency Departments or drug detoxification centers. Cocaine, chemically known as benzoylmethylecgonine, is a naturally occurring substance found in the leaves of the Erythroxylum coca plant. The pharmacokinetics of cocaine is dependent on multiple factors, such as physical/chemical form, route of administration, genetics and concurrent consumption of alcohol. This review aims to discuss metabolomics of cocaine, namely by presenting all known metabolites of cocaine and their roles in the cocaine-mediated toxic effects. PMID:26249365

  20. Probing Active Cocaine Vaccination Performance through Catalytic and Noncatalytic Hapten Design

    PubMed Central

    Cai, Xiaoqing; Whitfield, Timothy; Hixon, Mark S.; Grant, Yanabel; Koob, George F.; Janda, Kim D.

    2013-01-01

    Presently, there are no FDA-approved medications to treat cocaine addiction. Active vaccination has emerged as one approach to intervene through the rapid sequestering of the circulating drug, thus terminating both psychoactive effects and drug toxicity. Herein, we report our efforts examining two complimentary, but mechanistically distinct active vaccines, i.e., noncatalytic and catalytic, for cocaine treatment. A cocaine-like hapten GNE and a cocaine transition-state analogue GNT were used to generate the active vaccines, respectively. GNE-KLH was found to elicit persistent high-titer, cocaine-specific antibodies, and blunt cocaine induced locomotor behaviors. Catalytic antibodies induced by GNT-KLH were also shown to produce potent titers and suppress locomotor response in mice; however, upon repeated cocaine challenges the vaccine’s protecting effects waned. In depth kinetic analysis suggested that loss of catalytic activity was due to antibody modification by cocaine. The work provides new insights for the development of active vaccines for the treatment of cocaine abuse. PMID:23627877

  1. Cocaine psychosis.

    PubMed Central

    Baker, F. M.

    1989-01-01

    A 28-year-old divorced black male intranasal cocaine abuser presented three times in seven days to the psychiatric emergency service of a general hospital with complaints of psychotic symptoms in the context of a cocaine binge. His repeated visits provided the opportunity to correlate his clinical picture with serum cocaine levels. This article describes that correlation and reviews the current literature on cocaine abuse and the cocaine abstinence syndrome. PMID:2674466

  2. Empathic responsivity at 3 years of age in a sample of cocaine-exposed children.

    PubMed

    Schuetze, Pamela; Eiden, Rina D; Molnar, Danielle S; Colder, Craig D

    2014-01-01

    This study examined the association between prenatal exposure to cocaine and behavioral and physiological responsivity. Participants were 216 mother-infant dyads (116 cocaine exposed-CE, 100 nonexposed-NCE) recruited at birth. Measures of heart rate (HR) and respiratory sinus arrhythmia (RSA) were obtained during baseline and during a task designed to elicit empathy (exposure to infant crying). When the effects of prenatal cocaine use were examined in the context of polydrug use, results of model testing indicated that lower gestational age, prenatal exposure to cocaine and postnatal exposure to alcohol were each associated with a reduced suppression of RSA during the empathy task. These findings provide additional support for an association between prenatal cocaine exposure and dysregulation during early childhood during affect-eliciting environmental challenges. PMID:24444666

  3. Cocaine withdrawal symptoms identify "Type B" cocaine-dependent patients.

    PubMed

    Ahmadi, Jamshid; Kampman, Kyle; Dackis, Charles; Sparkman, Thorne; Pettinati, Helen

    2008-01-01

    Recent studies of substance dependence typologies briefly show that multivariate systems originally developed for identifying subtypes of alcoholics, such as Babor's Type A and B system, may also be valid in abusers of other substances, such as cocaine. Type B patients are characterized by an earlier onset of addiction and more severe symptoms of their addiction, psychopathology, and impulsivity. The Type B classification has also been associated with deficits in serotonergic function. We have found that patients who exhibit more severe cocaine withdrawal symptoms, as measured by scores on the Cocaine Selective Severity Assessment (CSSA), have poor treatment outcome and share many characteristics with "Type B" patients. In this paper, we review baseline characteristics of cocaine-dependent patients from several recently completed outpatient cocaine dependence treatment trials to assess the association of cocaine withdrawal symptom severity and the Type B profile. Identifying subtypes of cocaine-dependent patients may improve our ability to treat cocaine dependence by targeting treatments for specific subtypes of patients. We examined the ability of the CSSA scores to capture Type B characteristics in cocaine dependence by analyzing a series of cocaine medication trials that included 255 cocaine-dependent subjects. High CSSA scores at baseline were associated with a history of violent behavior, a family history of substance abuse, antisocial personality disorder, higher addiction severity, and co-morbid psychiatric diseases. Patients with high CSSA scores are also more likely to meet criteria for Type B (Type II) cocaine dependence. Identifying Type B cocaine-dependent patients may help to develop targeted psychosocial or pharmacological treatments for these difficult-to-treat patients.

  4. Prenatal and postnatal cocaine exposure predict teen cocaine use.

    PubMed

    Delaney-Black, Virginia; Chiodo, Lisa M; Hannigan, John H; Greenwald, Mark K; Janisse, James; Patterson, Grace; Huestis, Marilyn A; Partridge, Robert T; Ager, Joel; Sokol, Robert J

    2011-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n=316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use.

  5. Prenatal and postnatal cocaine exposure predict teen cocaine use

    PubMed Central

    Delaney-Black, Virginia; Chiodo, Lisa M.; Hannigan, John H.; Greenwald, Mark K.; Janisse, James; Patterson, Grace; Huestis, Marilyn A.; Partridge, Robert T.; Ager, Joel; Sokol, Robert J.

    2015-01-01

    Preclinical studies have identified alterations in cocaine and alcohol self-administration and behavioral responses to pharmacological challenges in adolescent offspring following prenatal exposure. To date, no published human studies have evaluated the relation between prenatal cocaine exposure and postnatal adolescent cocaine use. Human studies of prenatal cocaine-exposed children have also noted an increase in behaviors previously associated with substance use/abuse in teens and young adults, specifically childhood and teen externalizing behaviors, impulsivity, and attention problems. Despite these findings, human research has not addressed prior prenatal exposure as a potential predictor of teen drug use behavior. The purpose of this study was to evaluate the relations between prenatal cocaine exposure and teen cocaine use in a prospective longitudinal cohort (n = 316) that permitted extensive control for child, parent and community risk factors. Logistic regression analyses and Structural Equation Modeling revealed that both prenatal exposure and postnatal parent/caregiver cocaine use were uniquely related to teen use of cocaine at age 14 years. Teen cocaine use was also directly predicted by teen community violence exposure and caregiver negativity, and was indirectly related to teen community drug exposure. These data provide further evidence of the importance of prenatal exposure, family and community factors in the intergenerational transmission of teen/young adult substance abuse/use. PMID:20609384

  6. Cocaine withdrawal

    MedlinePlus

    ... is stopped or when a binge ends, a crash follows almost immediately. The cocaine user has a strong craving for more cocaine during a crash. Other symptoms include fatigue, lack of pleasure, anxiety, ...

  7. Hapten Optimization for Cocaine Vaccine with Improved Cocaine Recognition

    PubMed Central

    Ramakrishnan, Muthu; Kinsey, Berma M.; Singh, Rana A.; Kosten, Thomas R.; Orson, Frank M.

    2014-01-01

    In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anti-cocaine antibodies, none of the hapten was successfully designed which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl-norcocaine (HNC), bromoacetamido butyl- norcocaine (BNC), and succinyl-butyl- norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anti-cocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titer anti-cocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2β methyl ester group is hydrolyzed and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Though we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50) value for SBNC antibodies (2.8 μM) was significantly better than the SNC antibodies (9.4 μM) when respective hapten-BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4°C and 2-3 days in p

  8. Characteristics of pregnant women exposed to cocaine in Toronto between 1985 and 1990.

    PubMed Central

    Graham, K; Koren, G

    1991-01-01

    OBJECTIVE: To determine the characteristics of pregnant women exposed to cocaine. DESIGN: Case-control study. SETTING: Women attending the Motherisk Program, Hospital for Sick Children, Toronto, from September 1985 to March 1990. PATIENTS: All women who had admitted using cocaine before or during pregnancy. Of the two control groups the first comprised women who had admitted using cannabinoids but not cocaine before or during pregnancy and the second those who attended the clinic just before the cocaine case but who had not used illicit drugs. OUTCOME MEASURES: Age, marital status, ethnic background, number of pregnancies, children and elective or spontaneous abortions, socioeconomic status of woman and male partner, alcohol use, cigarette use, frequency of cocaine use and total amount taken. MAIN RESULTS: Of the 1625 women 91 (5.6%) admitted to using cocaine: 86 during the current pregnancy, 3 before the current pregnancy, 1 before planning a pregnancy and 1 during a previous pregnancy. None of the cocaine users were considered to be addicts; only 20% had used the drug more than 10 times. A total of 74 women used cannabinoids only. The mean age of the cocaine users was 27.1 (standard deviation [SD] 5.3) years; this was significantly lower than that of the control subjects (30.5 [SD 5.2] years) (p less than 0.001). More of the cocaine users than of the women in either of the two control groups were single (60% v. 38% and 14%, p less than 0.001). The cannabinoid users had significantly higher parity and the nonusers a significantly lower incidence of elective abortions than the cocaine users. The cocaine users had a significantly lower socioeconomic status than the control subjects (p less than 0.001); similarly, the male partners of the cocaine users had a significantly lower socioeconomic status than the partners of the control subjects (p = 0.001). CONCLUSIONS: Pregnant cocaine users who seek drug counselling represent a unique risk group, with clustering of

  9. Sex-Specific Dissociations in Autonomic and HPA Responses to Stress and Cues in Alcohol-Dependent Patients with Cocaine Abuse

    PubMed Central

    Fox, Helen C.; Hong, Kwang-Ik A.; Siedlarz, Kristen M.; Bergquist, Keri; Anderson, George; Kreek, Mary Jeanne; Sinha, Rajita

    2009-01-01

    Aims: Chronic alcohol and drug dependence leads to neuroadaptations in hypothalamic–pituitary–adrenal (HPA) and sympathetic adrenal medullary (SAM) stress systems, which impact response sensitivity to stress and alcohol cue and facilitates risk of relapse. To date, gender variations in these systems have not been fully assessed in abstinent alcohol-dependent individuals who also met criteria for cocaine abuse. Methods: Forty-two (21 M/21 F) early abstinent treatment-seeking substance-abusing (SA) men and women and 42 (21 M/21 F) healthy control (HC) volunteers were exposed to three 5-min guided imagery conditions (stress, alcohol/drug cue, neutral relaxing), presented randomly, one per day across three consecutive days. Alcohol craving and anxiety ratings were obtained as well as measures of heart rate (HR), blood pressure, plasma ACTH, cortisol, norepinephrine (NE) and epinephrine (EPI). Results: SA males showed increased ACTH and EPI basal tone compared with HC males and SA females. However, they demonstrated no increase in ACTH and cortisol levels following stress and alcohol cue imagery exposure compared to the neutral condition. SA females demonstrated a typically increased stress response in both measures. In addition, SA males showed no increase in cardiovascular response to either stress or cue, and no increase in catecholamine response to cue compared with their response to neutral imagery. Again, this dampening was not observed in HC males who produced significantly higher levels of cue-related HR and EPI, and significantly higher stress-related DBP. In contrast, SA females showed an enhanced ACTH and cortisol response to stress and cue compared with neutral imagery and this was not observed in the HC females. They also demonstrated a reduced increase in NE and EPI compared with both SA males and HC females as well as reduced HR compared with HC females. Conclusions: While SA males showed a generalized suppression of HPA, SAM system and cardiovascular

  10. The relationship between years of cocaine use and brain activation to cocaine and response inhibition cues

    PubMed Central

    Prisciandaro, James J.; Joseph, Jane E.; Myrick, Hugh; McRae-Clark, Aimee L.; Henderson, Scott; Pfeifer, James; Brady, Kathleen T.

    2014-01-01

    Aims Functional Magnetic Resonance Imaging research has attempted to elucidate the neurobehavioral underpinnings of cocaine dependence by evaluating differences in brain activation to cocaine and response inhibition cues between cocaine dependent individuals and controls. Less research has investigated associations between task-related brain activation and cocaine use characteristics; the present study was designed to address this gap in the literature. Design Cross-sectional. Setting The Center for Brain Imaging at the Medical University of South Carolina. Participants 51 cocaine users (41 dependent). Measurements Brain activation to cocaine-cue exposure and go no-go tasks in six a priori selected brain regions of interest and cocaine use characteristics (i.e., cocaine dependence status, years of cocaine use, cocaine use in the past 90 days) assessed via standardized interviews. Findings Participants demonstrated elevated activation to cocaine (bilateral ventral striatum, dorsal caudate, amygdala; mean F=19.00, mean p<.001) and response inhibition (bilateral anterior cingulate, insula, inferior frontal gyrus; mean F=7.01, mean p=.02) cues in all hypothesized brain regions. Years of cocaine use was associated with task-related brain activation, with more years of cocaine use associated with greater activation to cocaine cues in right (F=7.97,p=.01) and left (F=5.47,p=.02) ventral striatum and greater activation to response inhibition cues in left insula (F=5.10,p=.03) and inferior frontal gyrus (F=4.12,p=.05) controlling for age, cocaine dependence status, and cocaine use in the past 90 days. Conclusions Years of cocaine use may be more centrally related to cocaine cue and response inhibition brain activation as compared to cocaine dependence diagnosis or amount of recent use. PMID:24938849

  11. Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction

    SciTech Connect

    Moeller, S.J.; Goldstein, R.; Moeller, S.J.; Maloney, T. Parvaz, M.A.; Dunning, J.P.; Alia-Klein, N.; Woicik, P.A.; Hajcak, G.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2009-02-01

    Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. In two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm. Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal. Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use. Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.

  12. The neuropsychology of cocaine addiction: recent cocaine use masks impairment.

    PubMed

    Woicik, Patricia A; Moeller, Scott J; Alia-Klein, Nelly; Maloney, Thomas; Lukasik, Tanya M; Yeliosof, Olga; Wang, Gene-Jack; Volkow, Nora D; Goldstein, Rita Z

    2009-04-01

    Individuals with current cocaine use disorders (CUD) form a heterogeneous group, making sensitive neuropsychological (NP) comparisons with healthy individuals difficult. The current study examined the effects on NP functioning of four factors that commonly vary among CUD: urine status for cocaine (positive vs negative on study day), cigarette smoking, alcohol consumption, and dysphoria. Sixty-four cocaine abusers were matched to healthy comparison subjects on gender and race; the groups also did not differ in measures of general intellectual functioning. All subjects were administered an extensive NP battery measuring attention, executive function, memory, facial and emotion recognition, and motor function. Compared with healthy control subjects, CUD exhibited performance deficits on tasks of attention, executive function, and verbal memory (within one standard deviation of controls). Although CUD with positive urine status, who had higher frequency and more recent cocaine use, reported greater symptoms of dysphoria, these cognitive deficits were most pronounced in the CUD with negative urine status. Cigarette smoking, frequency of alcohol consumption, and dysphoria did not alter these results. The current findings replicate a previously reported statistically significant, but relatively mild NP impairment in CUD as compared with matched healthy control individuals and further suggest that frequent/recent cocaine use [corrected] may mask underlying cognitive (but not mood) disturbances. These results call for development of pharmacological agents targeted to enhance cognition, without negatively impacting mood in individuals addicted to cocaine.

  13. Cocaine (Coke, Crack) Facts

    MedlinePlus

    ... That People Abuse » Cocaine (Coke, Crack) Facts Cocaine (Coke, Crack) Facts Listen Cocaine is a white ... Version Download "My life was built around getting cocaine and getting high." Stacey is recovering from her ...

  14. Copper thiocyanato complexes and cocaine - a case of 'black cocaine'.

    PubMed

    Laussmann, Tim; Grzesiak, Ireneus; Krest, Alexander; Stirnat, Kathrin; Meier-Giebing, Sigrid; Ruschewitz, Uwe; Klein, Axel

    2015-01-01

    The chemical composition of a black powder confiscated by German customs was elucidated. Black powders are occasionally used as a 'transporter' for cocaine and are obviously especially designed to cloak the presence of the drug. The material consisting of cocaine, copper, iron, thiocyanate, and graphite was approached by analytical tools and chemical modelling. Graphite is added to the material probably with the intention of masking the typical infrared (IR) fingerprints of cocaine and can be clearly detected by powder X-ray diffraction (XRD) and Raman spectroscopy. Cu(2+) and NCS(-) ions, when carefully reacted with cocaine hydrochloride, form the novel compound (CocH)2 [Cu(NCS)4 ] (CocH(+)  = protonated cocaine), which has been characterised by single crystal XRD, IR, NMR, UV/Vis absorption and EPR spectroscopy. Based on some further experiments the assumed composition of the original black powder is discussed. PMID:24753444

  15. Effects of cocaine and cocaine metabolites on cardiovascular function in squirrel monkeys.

    PubMed

    Schindler, C W; Zheng, J W; Goldberg, S R

    2001-11-01

    The effects of cocaine and the cocaine metabolites norcocaine, ecgonine methyl ester, benzoylecgonine and cocaethylene were evaluated in conscious squirrel monkeys for their effects on blood pressure and heart rate. Norcocaine, ecgonine methyl ester and benzoylecgonine are produced in vivo following cocaine use. Cocaethylene is produced in vivo following concurrent cocaine and alcohol use. Increases in both blood pressure and heart rate were observed following cocaine doses of 0.3-3.0 mg/kg. Ecgonine methyl ester and benzoylecgonine had no effect on either parameter up to doses of 10.0 mg/kg. Norcocaine increased blood pressure, but was less potent than cocaine. Norcocaine did not affect heart rate at doses up to 3.0 mg/kg. In contrast to the other metabolites, cocaethylene increased blood pressure and heart rate similarly to cocaine. These results suggest that ecgonine methyl ester and benzoylecgonine are devoid of cardiovascular effects at doses comparable to cocaine and would not be expected to contribute to cocaine's overall cardiovascular effects. Norcocaine's effect on blood pressure might contribute to the cardiovascular effects of cocaine, but this metabolite is produced only at low levels in vivo. The one metabolite that might be expected to contribute to cocaine's overall cardiovascular effect is cocaethylene, although the degree of this contribution is not clear.

  16. DOE small scale fuel alcohol plant design

    SciTech Connect

    LaRue, D.M.; Richardson, J.G.

    1980-01-01

    The Department of Energy, in an effort to facilitate the deployment of rural-based ethanol production capability, has undertaken this effort to develop a basic small-scale plant design capable of producing anhydrous ethanol. The design, when completed, will contain all necessary specifications and diagrams sufficient for the construction of a plant. The design concept is modular; that is, sections of the plant can stand alone or be integrated into other designs with comparable throughput rates. The plant design will be easily scaled up or down from the designed flow rate of 25 gallons of ethanol per hour. Conversion factors will be provided with the final design package to explain scale-up and scale-down procedures. The intent of this program is to provide potential small-scale producers with sound information about the size, engineering requirements, costs and level of effort in building such a system.

  17. Alcohol

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Alcohol KidsHealth > For Teens > Alcohol Print A A A ... you can make an educated choice. What Is Alcohol? Alcohol is created when grains, fruits, or vegetables ...

  18. Hapten optimization for cocaine vaccine with improved cocaine recognition.

    PubMed

    Ramakrishnan, Muthu; Kinsey, Berma M; Singh, Rana A; Kosten, Thomas R; Orson, Frank M

    2014-09-01

    In the absence of any effective pharmacotherapy for cocaine addiction, immunotherapy is being actively pursued as a therapeutic intervention. While several different cocaine haptens have been explored to develop anticocaine antibodies, none of the hapten was successfully designed, which had a protonated tropane nitrogen as is found in native cocaine under physiological conditions, including the succinyl norcocaine (SNC) hapten that has been tested in phase II clinical trials. Herein, we discuss three different cocaine haptens: hexyl norcocaine (HNC), bromoacetamido butyl norcocaine (BNC), and succinyl butyl norcocaine (SBNC), each with a tertiary nitrogen structure mimicking that of native cocaine which could optimize the specificity of anticocaine antibodies for better cocaine recognition. Mice immunized with these haptens conjugated to immunogenic proteins produced high titre anticocaine antibodies. However, during chemical conjugation of HNC and BNC haptens to carrier proteins, the 2β methyl ester group is hydrolyzed, and immunizing mice with these conjugate vaccines in mice produced antibodies that bound both cocaine and the inactive benzoylecgonine metabolite. While in the case of the SBNC conjugate, vaccine hydrolysis of the methyl ester did not appear to occur, leading to antibodies with high specificity to cocaine over BE. Although we observed similar specificity with a SNC hapten, the striking difference is that SBNC carries a positive charge on the tropane nitrogen atom, and therefore, it is expected to have better binding of cocaine. The 50% cocaine inhibitory concentration (IC50 ) value for SBNC antibodies (2.8 μm) was significantly better than the SNC antibodies (9.4 μm) when respective hapten-BSA was used as a substrate. In addition, antibodies from both sera had no inhibitory effect from BE. In contrast to BNC and HNC, the SBNC conjugate was also found to be highly stable without any noticeable hydrolysis for several months at 4 °C and 2-3

  19. Modulating Cocaine Vaccine Potency Through Hapten Fluorination

    PubMed Central

    Cai, Xiaoqing; Tsuchikama, Kyoji; Janda, Kim D.

    2013-01-01

    Cocaine addiction is a long-lasting relapsing illness characterized by cycles of abuse, abstinence and reinstatement, and antibody-based therapies could be a powerful therapeutic approach. Herein, we explored the possibility of using halogenated cocaine haptens to enhance the immunological properties of anti-cocaine vaccines. Three fluorine-containing cocaine haptens (GNF, GNCF and GN5F) and one chlorine-containing cocaine hapten (GNCl) were designed and synthesized, based upon the chemical scaffold of the only hapten that has reached clinical trials, succinyl norcocaine (SNC). Hapten GNF was found to retain potent cocaine affinity, and also elicit antibodies in a higher concentration than the parent structure SNC. Our data suggests that strategic hapten fluorination could be useful for not only improving upon the current cocaine vaccine undergoing clinical trials, but it may also be a valuable new approach, with application to any of the vaccines being developed for the treatment of drugs of abuse. PMID:23398531

  20. Cocaine. Specialized Information Service.

    ERIC Educational Resources Information Center

    Do It Now Foundation, Phoenix, AZ.

    This compilation of journal articles on cocaine includes a report describing cocaine as the recreational drug of the middle class, statistics from the United States Department of Health on health consequences of cocaine use, an article on "speedballing" (use of cocaine and heroin in combination), and a discussion of the various ways cocaine is…

  1. Alcohol

    MedlinePlus

    ... Text Size: A A A Listen En Español Alcohol Wondering if alcohol is off limits with diabetes? Most people with diabetes can have a moderate amount of alcohol. Research has shown that there can be some ...

  2. Alcohol

    MedlinePlus

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  3. Mind Over Matter: Cocaine

    MedlinePlus

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Cocaine Print Mind Over Matter: Cocaine Order Free Publication in: English Spanish Download PDF 806.08 KB Cocaine is made ...

  4. Prenatal Cocaine Exposure: Drug and Environmental Effects at 9 years

    PubMed Central

    Singer, Lynn T.; Nelson, Suchitra; Short, Elizabeth; Min, Meeyoung O.; Kirchner, H. Lester; Lewis, Barbara; Russ, Sandra; Minnes, Sonia

    2008-01-01

    Objective To assess school age cognitive and achievement outcomes after prenatal cocaine exposure, controlling for confounding drug and environmental factors. Study design At 9 years, 371 children (192 cocaine exposure, CE; 179 non-exposure, NCE) were assessed for IQ and school achievement in a longitudinal, prospective study from birth. An extensive number of confounding variables were controlled, including quality of caregiving environment, polydrug exposure, lead, iron deficiency anemia (IDA), and foster/adoptive care. Results CE predicted poorer Perceptual Reasoning IQ with a linear relationship of the concentration of the cocaine metabolite, benzoylecgonine, to degree of impairment. Effects were mediated through birth head circumference, indicating a relationship with fetal brain growth. Negative effects of alcohol, lead, and marijuana exposure and positive effects of home environment were additive. Children with CE in foster/adoptive care had better home environments and lower lead levels. School achievement was not affected. Conclusions There were persistent teratologic effects of CE on specific cognitive functions and additive effects of alcohol, lead, marijuana, IDA, and home environment. Documenting environmental factors in behavioral teratology studies is important because in this sample, CE was associated with better home environments and lower environmental risk for a substantial number of children. PMID:18571546

  5. Alcohol

    MedlinePlus

    ... Got Homework? Here's Help White House Lunch Recipes Alcohol KidsHealth > For Kids > Alcohol Print A A A Text Size What's in ... What Is Alcoholism? Say No en español El alcohol Getting the Right Message "Hey, who wants a ...

  6. Developmental trajectories of cocaine-and-other-drug-exposed and non-cocaine-exposed children.

    PubMed

    Mayes, Linda C; Cicchetti, Domenic; Acharyya, Suddhasatta; Zhang, Heping

    2003-10-01

    Few data are available concerning the trajectories of mental and motor development across time for cocaine-exposed children compared with others. Findings are presented from individual group curve analyses of the mental and motor development measured by the Bayley Scales of Infant Development-II (BSID-II) on repeated visits from 3 through 36 months of a group of prenatally cocaine-and-other-drug-exposed children (n = 265) compared with those exposed to no drugs (n = 129) or no-cocaine-but-other-drugs (n = 66), including alcohol and/or tobacco. Across time, there was a general decline in motor performance but cocaine-exposed-infants showed a trend toward a greater decrease than children in the other two comparison groups. For mental performance, there was also a decline across age but only through 24 months and no differences in the trajectory of the cocaine-exposed group compared to the other two. And, across all assessment ages, cocaine-exposed-infants showed lower BSID-II mental performance compared to both non-drug and non-cocaine-exposed children. Results suggest that prenatally cocaine-exposed children show delayed developmental indices, particularly in their mental performance, but their trajectories across time are similar to those from impoverished, non-cocaine-exposed groups. PMID:14578693

  7. Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus

    PubMed Central

    Koob, George; Hicks, Martin J.; Wee, Sunmee; Rosenberg, Jonathan B.; De, Bishnu P.; Kaminksy, Stephen M.; Moreno, Amira; Janda, Kim D.; Crystal, Ronald G.

    2012-01-01

    The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1−E3− serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts. PMID:22229312

  8. Filthy Lucre: The Chemical Detection of Cocaine-Contaminated Currency.

    ERIC Educational Resources Information Center

    Acheson, Ed

    2001-01-01

    Discusses the problem of seizing cocaine-tainted money. Describes an experiment designed to determine what percentage of paper currency is contaminated with cocaine. Considers sampling, the analysis method, contamination, levels of cocaine in money and criminal activity, and the reliability of results. (SAH)

  9. Valproate treatment and cocaine cue reactivity in cocaine-dependent individuals

    PubMed Central

    Reid, Malcolm S.; Thakkar, Vatsal

    2009-01-01

    Based on prior clinical trials indicating that γ-aminobutyric acid (GABA) based anticonvulsant medications reduce drug craving in cocaine dependent study participants, we tested the effects of valproate treatment on cue-induced cocaine craving. Crack cocaine dependent individuals (N=20) were tested in a randomized, placebo-controlled, within-subjects, crossover study design. Valproate treatment was titrated up to 1500 mg/day by Day 6 of treatment, cue testing was completed on Day 8 of treatment, and all study participants underwent a washout period of 5 days between active and placebo medication treatment periods. Testing included both cocaine and neutral cue exposure sessions, presented in a random and counterbalanced order. Main effects of cue exposure were found for subjective ratings of “desire to use cocaine now”, the cocaine craving index, cocaine-like high, and cocaine withdrawal. Treatment interaction effects were found with “desire to use cocaine now”, which underwent a greater increase following cocaine cue exposure in the valproate condition. Main effects of medication treatment were found, in which lower blood pressure and heart rate, and higher plasma cortisol levels, were associated with valproate treatment. Valproate treatment was also associated, at a trend level, with higher pre-test cocaine craving levels. The results demonstrate that cocaine cue reactivity is a robust phenomena across two assessment sessions, but fail to support the use of valproate as a means of reducing spontaneous and cue-induced cocaine craving. The use of valproate as a treatment for cocaine dependence is not supported. PMID:19375250

  10. Alcoholism

    PubMed Central

    Girard, Donald E.; Carlton, Bruce E.

    1978-01-01

    There are important measurements of alcoholism that are poorly understood by physicians. Professional attitudes toward alcoholic patients are often counterproductive. Americans spend about $30 billion on alcohol a year and most adults drink alcohol. Even though traditional criteria allow for recognition of the disease, diagnosis is often made late in the natural course, when intervention fails. Alcoholism is a major health problem and accounts for 10 percent of total health care costs. Still, this country's 10 million adult alcoholics come from a pool of heavy drinkers with well defined demographic characteristics. These social, cultural and familial traits, along with subtle signs of addiction, allow for earlier diagnosis. Although these factors alone do not establish a diagnosis of alcoholism, they should alert a physician that significant disease may be imminent. Focus must be directed to these aspects of alcoholism if containment of the problem is expected. PMID:685264

  11. Lack of effect of ethanol on cocaine prime-induced reinstatement of extinguished cocaine self-administration in rhesus monkeys.

    PubMed

    Czoty, Paul W

    2016-10-01

    Cocaine and alcohol are commonly co-abused for reasons that are incompletely understood. Laboratory animal studies have suggested that, although the reinforcing effects of low cocaine doses are increased following chronic ethanol (EtOH) consumption, acute EtOH administration does not consistently alter cocaine self-administration. The present study examined whether EtOH influences another abuse-related effect of cocaine: reinstatement of extinguished responding. Rhesus monkeys that had previously consumed EtOH for 8 weeks (2.0 g/kg over 1 h, 5 days/week) self-administered up to 10 injections per day of 0.1 mg/kg cocaine under a fixed-interval 300-s schedule. After responding had been extinguished by substituting saline for cocaine, a pre-session infusion of saline or EtOH (0.5 or 1.0 g/kg, intravenously over 10 min) was followed by a 'priming' injection of saline or cocaine (intravenously). Responding was increased significantly by priming injections of cocaine, but not saline. EtOH infusions neither reinstated behavior when administered before a saline prime nor altered the priming effect of cocaine. The inability of EtOH to alter the response-reinstating ability of cocaine provides further evidence for a lack of acute behavioral interactions between cocaine and EtOH. PMID:27509315

  12. Comparative behavioral pharmacology and toxicology of cocaine and its ethanol-derived metabolite, cocaine ethyl-ester (cocaethylene)

    SciTech Connect

    Katz, J.L.; Terry, P.; Witkin, J.M. )

    1992-01-01

    The present study compared the behavioral and toxic effects of cocaine and its ethanol derived metabolite, cocaine ethyl-ester (cocaethylene). Both drugs produced qualitatively similar psychomoter stimulant effects. Cocaine and cocaethylene increased locomotor activity in mice, with cocaine approximately four times more potent than cocaethylene. The durations of action of ED{sub 75} doses of each of the drugs were comparable. Each of the drugs also produced stimulation of operant responding in rats. In rats and squirrel monkeys trained to discriminate cocaine injections from saline, cocaine was approximately three to five times more potent than cocaethylene in producing these cocaine-like interoceptive effects. In contrast to the behavioral effects, cocaine and cocaethylene were equipotent in producing convulsions, and cocaethylene was more potent than cocaine in producing lethality. These results suggest that the conversion of cocaine to cocaethylene with simultaneous cocaine and alcohol use may produce an increased risk of toxicity due to a decrease in the potency of cocaethylene in producing psychomotor stimulant effects, and its increased potency in producing toxicity.

  13. Prenatal Cocaine Exposure Alters Cortisol Stress Reactivity in 11 Year Old Children

    PubMed Central

    Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Lin, Richard; Das, Abhik; Higgins, Rosemary

    2011-01-01

    Objective Determine the association between prenatal cocaine exposure and postnatal environmental adversity on salivary cortisol stress reactivity in school aged children. Study design Subjects included 743 11 year old children (n=320 cocaine exposed; 423 comparison) followed since birth in a longitudinal prospective multisite study. Saliva samples were collected to measure cortisol at baseline and after a standardized procedure to induce psychological stress. Children were divided into those who showed an increase in cortisol from baseline to post stress and those who showed a decrease or blunted cortisol response. Covariates measured included site, birthweight, maternal pre and postnatal use of alcohol, tobacco or marijuana, social class, changes in caretakers, maternal depression and psychological symptoms, domestic and community violence, child abuse and quality of the home. Results With adjustment for confounding variables, cortisol reactivity to stress was more likely to be blunted in children with prenatal cocaine exposure. Cocaine exposed children exposed to domestic violence showed the strongest effects. Conclusion The combination of prenatal cocaine exposure and an adverse postnatal environment could down regulate the hypothalamic-pituitary-adrenal axis (HPA) resulting in the blunted cortisol response to stress possibly increasing risk for later psychopathology and adult disease. PMID:20400094

  14. Young people, alcohol, and designer drinks: quantitative and qualitative study.

    PubMed Central

    Hughes, K.; MacKintosh, A. M.; Hastings, G.; Wheeler, C.; Watson, J.; Inglis, J.

    1997-01-01

    OBJECTIVE: To examine the appeal of "designer drinks" to young people. DESIGN: Qualitative and quantitative research comprising group discussions and questionnaire led interviews with young people accompanied by a self completion questionnaire. SETTINGS: Argyll and Clyde Health Board area, west Scotland. SUBJECTS: Eight groups aged 12-17 years; 824 aged 12-17 recruited by multistage cluster probability sample from the community health index. RESULTS: Young people were familiar with designer drinks, especially MD 20/20 and leading brands of strong white cider. Attitudes towards these drinks varied quite distinctly with age, clearly reflecting their attitudes towards and motivations for drinking in general. The brand imagery of designer drinks-in contrast with that of more mainstream drinks-matched many 14 and 15 year olds' perceptions and expectations of drinking. Popularity of designer drinks peaked between the ages of 13 and 16 while more conventional drinks showed a consistent increase in popularity with age. Consumption of designer drinks tended to be in less controlled circumstances and was associated with heavier alcohol intake and greater drunkenness. CONCLUSIONS: Designer drinks are a cause for concern. They appeal to young people, often more so than conventional drinks, and are particularly attractive to 14-16 year olds. Consumption of designer drinks is also associated with drinking in less controlled environments, heavier drinking, and greater drunkenness. There is a need for policy debate to assess the desirability of these drinks and the extent to which further controls on their marketing are required. PMID:9040387

  15. Influence of abstinence and conditions of cocaine access on the reinforcing strength of cocaine in nonhuman primates.

    PubMed

    Czoty, Paul W; Martelle, Jennifer L; Nader, Michael A

    2006-12-01

    The development of addiction is marked by a transition from recreational to uncontrolled drug use. Investigators modeling this phenomenon in rodents observed increases in cocaine self-administration when conditions of drug access were altered as well as after abstinence. The present studies were designed to extend this research to nonhuman primates by examining whether the reinforcing strength of cocaine could be altered by changing conditions of cocaine availability or by introducing abstinence periods. Rhesus monkeys self-administered cocaine (0.03-0.3 mg/kg per injection) under a progressive-ratio (PR) schedule of reinforcement in evening sessions, with the number of injections earned serving as a measure of reinforcing strength. Alterations in the reinforcing strength of cocaine were assessed after additional access to cocaine under a fixed-ratio (FR) schedule was provided in morning sessions and following various periods of abstinence (3, 7 and 14 days) from regimens of self-administration that resulted in a range of cocaine intakes. Under baseline PR conditions, the maximum number of cocaine injections increased dose-dependently, peaking when 0.3 mg/kg per injection cocaine was available. No increases in the reinforcing strength of cocaine were observed under any condition. In contrast, a statistically significant decrease in the reinforcing strength of cocaine was observed following 14 days of abstinence under one condition. These results fail to support the views that increasing access to cocaine or abstinence enhances the reinforcing strength of cocaine. PMID:16730922

  16. Chronic Inhibition of Dopamine β-Hydroxylase Facilitates Behavioral Responses to Cocaine in Mice

    PubMed Central

    Gaval-Cruz, Meriem; Liles, Larry Cameron; Iuvone, Paul Michael; Weinshenker, David

    2012-01-01

    The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh −/−) mice, disulfiram, and the selective DBH inhibitor, nepicastat. Locomotor activity was measured in control (Dbh +/−) and Dbh −/− mice during a 5 day regimen of saline+saline, disulfiram+saline, nepicastat+saline, saline+cocaine, disulfiram+cocaine, or nepicastat+cocaine. After a 10 day withdrawal period, all groups were administered cocaine, and locomotor activity and stereotypy were measured. Drug-naïve Dbh −/− mice were hypersensitive to cocaine-induced locomotion and resembled cocaine-sensitized Dbh +/− mice. Chronic disulfiram administration facilitated cocaine-induced locomotion in some mice and induced stereotypy in others during the development of sensitization, while cocaine-induced stereotypy was evident in all nepicastat-treated mice. Cocaine-induced stereotypy was profoundly increased in the disulfiram+cocaine, nepicastat+cocaine, and nepicastat+saline groups upon cocaine challenge after withdrawal in Dbh +/− mice. Disulfiram or nepicastat treatment had no effect on behavioral responses to cocaine in Dbh −/− mice. These results demonstrate that chronic DBH inhibition facilitates behavioral responses to cocaine, although different methods of inhibition (genetic vs. non-selective inhibitor vs. selective inhibitor) enhance qualitatively different cocaine-induced behaviors. PMID:23209785

  17. Purpose in Life Predicts Treatment Outcome Among Adult Cocaine Abusers in Treatment

    PubMed Central

    Martin, Rosemarie A.; MacKinnon, Selene; Johnson, Jennifer; Rohsenow, Damaris J.

    2010-01-01

    A sense of purpose in life has been positively associated with mental health and well-being and has been negatively associated with alcohol use in correlational and longitudinal studies, but has not been studied as a predictor of cocaine treatment outcome. This study examined pre-treatment purpose in life as a predictor of response to a 30-day residential substance use treatment program among 154 participants with cocaine dependence. Purpose in life was unrelated to cocaine or alcohol use during the 6 months pretreatment. After controlling for age, baseline use, and depressive symptoms, purpose in life significantly (p < .01) predicted relapse to any use of cocaine and to alcohol, and the number of days cocaine or alcohol was used in the six months after treatment. Findings suggest that increasing purpose in life may be an important aspect of treatment among cocaine dependent patients. PMID:21129893

  18. Experimental manipulation of cocaine craving by videotaped environmental cues.

    PubMed

    Kilgus, M D; Pumariega, A J

    1994-11-01

    Thirteen male patients consecutively admitted to an inpatient drug and alcohol rehabilitation hospital with the primary diagnosis of crack cocaine dependence were shown a 30-minute videotape that included salient environmental cues intended to elicit cocaine craving. The subjects were tested before and after the videotape by the use of a continuous 20-cm analogue visual instrument that asks them to rate their perceived degree of craving, mood, energy, and wellness. Only craving showed a statistically significant change from pretest to posttest. Correlations among the four separate ratings suggest that mood and craving are different dimensions that independently contribute to one's general sense of well-being. This study demonstrates that cocaine craving can be induced in a group setting by presenting certain visual and auditory cues on a video monitor. The procedure of obtaining self-ratings in response to videotaped environmental cues could be easily incorporated into research methods designed to assess pharmacologic efficacy in reducing the intense craving that reinforces addiction.

  19. Adenovirus Capsid-Based Anti-Cocaine Vaccine Prevents Cocaine from Binding to the Nonhuman Primate CNS Dopamine Transporter

    PubMed Central

    Maoz, Anat; Hicks, Martin J; Vallabhjosula, Shankar; Synan, Michael; Kothari, Paresh J; Dyke, Jonathan P; Ballon, Douglas J; Kaminsky, Stephen M; De, Bishnu P; Rosenberg, Jonathan B; Martinez, Diana; Koob, George F; Janda, Kim D; Crystal, Ronald G

    2013-01-01

    Cocaine addiction is a major problem for which there is no approved pharmacotherapy. We have developed a vaccine to cocaine (dAd5GNE), based on the cocaine analog GNE linked to the capsid proteins of a serotype 5 adenovirus, designed to evoke anti-cocaine antibodies that sequester cocaine in the blood, preventing access to the CNS. To assess the efficacy of dAd5GNE in a large animal model, positron emission tomography (PET) and the radiotracer [11C]PE2I were used to measure cocaine occupancy of the dopamine transporter (DAT) in nonhuman primates. Repeat administration of dAd5GNE induced high anti-cocaine titers. Before vaccination, cocaine displaced PE2I from DAT in the caudate and putamen, resulting in 62±4% cocaine occupancy. In contrast, dAd5GNE-vaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4 × 105, the cocaine occupancy was reduced to levels of <20%, significantly below the 47% threshold required to evoke the subjective ‘high' reported in humans. PMID:23660705

  20. Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter.

    PubMed

    Maoz, Anat; Hicks, Martin J; Vallabhjosula, Shankar; Synan, Michael; Kothari, Paresh J; Dyke, Jonathan P; Ballon, Douglas J; Kaminsky, Stephen M; De, Bishnu P; Rosenberg, Jonathan B; Martinez, Diana; Koob, George F; Janda, Kim D; Crystal, Ronald G

    2013-10-01

    Cocaine addiction is a major problem for which there is no approved pharmacotherapy. We have developed a vaccine to cocaine (dAd5GNE), based on the cocaine analog GNE linked to the capsid proteins of a serotype 5 adenovirus, designed to evoke anti-cocaine antibodies that sequester cocaine in the blood, preventing access to the CNS. To assess the efficacy of dAd5GNE in a large animal model, positron emission tomography (PET) and the radiotracer [(11)C]PE2I were used to measure cocaine occupancy of the dopamine transporter (DAT) in nonhuman primates. Repeat administration of dAd5GNE induced high anti-cocaine titers. Before vaccination, cocaine displaced PE2I from DAT in the caudate and putamen, resulting in 62±4% cocaine occupancy. In contrast, dAd5GNE-vaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4 × 10(5), the cocaine occupancy was reduced to levels of <20%, significantly below the 47% threshold required to evoke the subjective 'high' reported in humans. PMID:23660705

  1. Prenatal Cocaine Exposure and Infant Cortisol Reactivity

    PubMed Central

    Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.

    2009-01-01

    This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed, and children's saliva was sampled before, during, and after standardized procedures designed to elicit emotional arousal. Results revealed cocaine-exposed infants had a high amplitude trajectory of cortisol reactivity compared to non-cocaine-exposed infants. Infant gender and caregiving instability moderated this association. The findings support a dual hazard vulnerability model and have implications for evolutionary-developmental theories of individual differences in biological sensitivity to context. PMID:19467009

  2. Sex differences in cocaine use and experiences: a double standard revived?

    PubMed

    Erickson, P G; Murray, G F

    1989-01-01

    Women's use of prescription medication exceeds that of men's and yet is not viewed with the alarm and disapproval that accompanies women's lower levels of use of alcohol and illicit drugs. Reports in the media, based on anecdotal accounts, have identified women as a group at particular risk for cocaine addiction and have suggested that their problems with cocaine are greater than men's. After reviewing the scientific literature and analyzing the results of an original research study, this paper argues that there is no evidence that women's cocaine use exceeds that of men's, that women's rates of use are growing faster than men's, or that female cocaine users experience more problems than male cocaine users. Since the deviant image of the female cocaine user is a social construction lacking a factual basis, we conclude that a different standard is being applied to women who use cocaine than to men who use cocaine.

  3. Cocaine and Cardiovascular Events.

    ERIC Educational Resources Information Center

    Cantwell, John D.; Rose, Fred D.

    1986-01-01

    The case of a 21-year-old man who suffered a myocardial infarction after using cocaine and amphetamines is reported. A brief literature review provides evidence of cocaine's potential cardiovascular effects. (Author/MT)

  4. Alcohol.

    ERIC Educational Resources Information Center

    Schibeci, Renato

    1996-01-01

    Describes the manufacturing of ethanol, the effects of ethanol on the body, the composition of alcoholic drinks, and some properties of ethanol. Presents some classroom experiments using ethanol. (JRH)

  5. Teaching Experimental Design Using a GC MS Analysis of Cocaine on Money: A Cross-Disciplinary Laboratory 1254 Christopher A. Heimbuck and Nathan W. Bower Quantitative Determination of Nicotine and Cotinine in Urine and Sputum Using a Combined SPME-GC/MS Method

    NASA Astrophysics Data System (ADS)

    Witter, A. E.; Klinger, D. M.; Fan, X.; Lam, M.; Mathers, D. T.; Mabury, S. A.

    2002-10-01

    The forensic analysis of cocaine on currencies was optimized using a fractional, two-level experimental design that compared methanol and HCl extraction, SPE versus heptane pre-concentration, and extracted versus total ion chromatography. Subsequent student-initiated questions about levels of cocaine on U.S. and world currencies helped make connections to societal issues while teaching method optimization and chromatography. A significant correlation was found between the levels of cocaine and the age of the bills. Levels of cocaine on various world currencies followed expected drug-trafficking patterns with the highest levels found in the most developed countries.

  6. Conditioned Contribution of Peripheral Cocaine Actions to Cocaine Reward and Cocaine-Seeking

    PubMed Central

    Wang, Bin; You, Zhi-Bing; Oleson, Erik B; Cheer, Joseph F; Myal, Stephanie; Wise, Roy A

    2013-01-01

    Cocaine has actions in the peripheral nervous system that reliably precede—and thus predict—its soon-to-follow central rewarding effects. In cocaine-experienced animals, the peripheral cocaine signal is relayed to the central nervous system, triggering excitatory input to the ventral tegmental origin of the mesocorticolimbic dopamine system, the system that mediates the rewarding effects of the drug. We used cocaine methiodide, a cocaine analog that does not cross the blood–brain barrier, to isolate the peripheral actions of cocaine and determine their central and behavioral effects in animals first trained to lever-press for cocaine hydrochloride (the centrally acting and abused form of the drug). We first confirmed with fast-scan cyclic voltammetry that cocaine methiodide causes rapid dopamine release from dopamine terminals in cocaine hydrochloride-trained rats. We then compared the ability of cocaine hydrochloride and cocaine methiodide to establish conditioned place preferences in rats with self-administration experience. While cocaine hydrochloride established stronger place preferences, cocaine methiodide was also effective and its effectiveness increased (incubated) over weeks of cocaine abstinence. Cocaine self-administration was extinguished when cocaine methiodide or saline was substituted for cocaine hydrochloride in the intravenous self-administration paradigm, but cocaine hydrochloride and cocaine methiodide each reinstated non-rewarded lever-pressing after extinction. Rats extinguished by cocaine methiodide substitution showed weaker cocaine-induced reinstatement than rats extinguished by saline substitution. These findings suggest that the conditioned peripheral effects of cocaine can contribute significantly to cocaine-induced (but not stress-induced) cocaine craving, and also suggest the cocaine cue as an important target for cue-exposure therapies for cocaine addiction. PMID:23535778

  7. Characteristics of Rural Crack and Powder Cocaine Users: Gender and Other Correlates

    PubMed Central

    Pope, Sandra K.; Falck, Russel S.; Carlson, Robert G.; Leukefeld, Carl; Booth, Brenda M.

    2013-01-01

    Background Little is known about the relationship of gender with cocaine use in rural areas. This study describes these relationships among stimulant users residing in rural areas of Arkansas, Kentucky and Ohio. Objectives Understanding characteristics of crack and powder cocaine users in rural areas may help inform prevention, education and treatment efforts to address rural stimulant use. Methods Participants were 690 stimulant users, including 274 (38.6%) females, residing in 9 rural counties. Cocaine use was measured by self-report of cocaine use, frequency of use, age of first use, and cocaine abuse/dependence. Powder cocaine use was reported by 49% of this sample of stimulant users and 59% reported using crack cocaine. Findings Differing use patterns emerged for female and male cocaine users in this rural sample; females began using alcohol, marijuana, and cocaine at later ages than males but there were no gender differences in current powder cocaine use. Females reported more frequent use of crack cocaine and more cocaine abuse/dependence than males, and in regression analyses, female crack cocaine users had 1.8 times greater odds of reporting frequent crack use than male crack users. Conclusions and Scientific Significance These findings suggest differing profiles and patterns of cocaine use for male and female users in rural areas, supporting previous findings in urban areas of gender-based vulnerability to negative consequences of cocaine use. Further research on cocain use in rural areas can provide insights into gender differences that can inform development and refinement of effective interventions in rural communities. PMID:21851207

  8. Effects of prenatal cocaine exposure on infant reactivity and regulation

    PubMed Central

    Eiden, Rina D.; McAuliffe, Shannon; Kachadourian, Lorig; Coles, Claire; Colder, Craig; Schuetze, Pamela

    2009-01-01

    The purpose of this study was to examine the role of prenatal cocaine exposure and associated risk factors on infant reactivity and regulation at 7 months of infant age. Participants consisted of 167 mother-infant dyads participating in an ongoing longitudinal study of prenatal cocaine exposure, who completed the arm-restraint procedure at the 7-month assessment (87 cocaine exposed, 80 non-cocaine exposed). We hypothesized that cocaine exposed infants would display higher arousal or reactivity and lower regulation during a procedure designed to arouse anger/frustration. Results indicated that cocaine exposed infants were more reactive to increases in the level of stress from trial 1 to trial 2 but exhibited no change in the number of regulatory strategies as stress increased, unlike the control group infants. Infant birth weight moderated the association between cocaine exposure and infant regulation. Among cocaine exposed infants, those with lower birth weight displayed higher reactivity compared to those with higher birth weight. Contrary to expectations, there were no indirect effects between cocaine exposure and infant reactivity/regulation via environmental risk, parenting, or birth weight. Results are supportive of a teratological model of prenatal cocaine exposure for infant reactivity/regulation in infancy. PMID:18822371

  9. Cocaine downregulates beta-adrenergic receptors in pregnant sheep myometrium.

    PubMed

    Wang, F L; Gauvin, J M; Dombrowski, M P; Smith, Y R; Christopher, K A; Hurd, W W

    1996-01-01

    Cocaine abuse is associated with premature labor. Although cocaine is known to competitively inhibit beta-adrenergic receptor binding, cocaine's effect on receptor downregulation is uncertain. This study was designed to determine the in vitro effect of cocaine on downregulation of beta-adrenergic receptors in pregnant myometrium. Pregnant sheep myometrium was incubated with either cocaine, isoproterenol, or a cocaine metabolite, benzoylecgonine. Membrane fractions were assayed for beta-adrenergic receptors using (125I)-cyanopindolol and the beta 2-adrenergic antagonist ICI 118,551. We found that cocaine (10(-6) to 10(-4) mol/L), but not benzoylecgonine, downregulated both beta 1- and beta 2-adrenergic receptors, but did not further augment receptor downregulation by isoproterenol. The 46% decrease in beta-adrenergic receptors seen after exposure to cocaine was similar to the 53% decrease seen after isoproterenol. We hypothesize downregulation of beta-adrenergic receptors by cocaine may play a role in the association of cocaine abuse with premature labor.

  10. Gambling Problems Among Community Cocaine Users.

    PubMed

    Dufour, Magali; Nguyen, Noël; Bertrand, Karine; Perreault, Michel; Jutras-Aswad, Didier; Morvannou, Adèle; Bruneau, Julie; Berbiche, Djamal; Roy, Élise

    2016-09-01

    Cocaine use is highly prevalent and a major public health problem. While some studies have reported frequent comorbidity problems among cocaine users, few studies have included evaluation of gambling problems. This study aimed to estimate the prevalence of gambling problems and compare those who were at-risk gamblers with non-problem gamblers in terms of mental health problems, substance use problems, and some risk factors (i.e. family antecedents, erroneous perceptions and coping strategies) among individuals who smoke or inject cocaine. A total of 424 smoked or injected cocaine users recruited through community-based programs in Montreal (Quebec) completed the questionnaire, including the Canadian Pathological Gambling Index, the Composite International Diagnostic Interview, the CAGE, and the Severity Dependence Scale. Of the sample, 18.4 % were considered at-risk gamblers, of whom 7.8 % had problems gambling and 10.6 % were moderate-risk gamblers. The at-risk group was more likely to have experienced a recent phobic disorder and alcohol problems than the non-problem group. A multivariate analysis showed that, compared to those who were non-problem gamblers, the at-risk ones were more likely to have lost a large sum of money when they first started gambling, believed that their luck would turn, and gambled in reaction to painful life events. These results indicate the need to include routines for screening to identify gambling problem among cocaine users. PMID:26983825

  11. Cocaine-related deaths.

    PubMed

    Lora-Tamayo, C; Tena, T; Rodriguez, A

    1994-07-15

    Cocaine availability has been increasing in Spain in the past few years. A review of all the toxicological analyses carried out at the Madrid Department of the Instituto Nacional de Toxicología, with subjects who had died of drugs from 1990 to 1992, found 533 persons who had cocaine in their blood and/or tissues; 450 (84%) deaths involved cocaine and heroin together whereas 83 (16%) deaths involved cocaine with an absence of heroin. This paper reports the circumstances, cocaine and benzoylecgonine concentrations in the blood and other toxicological findings for the two major groups of deaths where cocaine was found with an absence of heroin, i.e., possible overdose cases (35 cases) and traffic accidents (23 cases).

  12. “We as Drug Addicts Need that Program”: Insight from Rural African American Cocaine Users on Designing a Sexual Risk Reduction Intervention for Their Community

    PubMed Central

    Montgomery, Brooke E. E.; Stewart, Katharine E.; Wright, Patricia B.; McSweeney, Jean; Booth, Brenda M.

    2013-01-01

    This focused ethnographic study examines data collected in 2007 from four gender- and age-specific focus groups (FGs) (N = 31) to inform the development of a sexual risk reduction intervention for African American cocaine users in rural Arkansas. A semi-structured protocol was used to guide audio-recorded FGs. Data were entered into Ethnograph and analyzed using constant comparison and content analysis. Four codes with accompanying factors emerged from the data and revealed recommendations for sexual risk reduction interventions with similar populations. Intervention design implications and challenges, study limitations, and future research are discussed. The study was supported by funds from the National Institute of Nursing Research (P20 NR009006-01) and the National Institute on Drug Abuse (1R01DA024575-01 and F31 DA026286-01). PMID:22216991

  13. "We as drug addicts need that program": Insight from rural African American cocaine users on designing a sexual risk reduction intervention for their community.

    PubMed

    Montgomery, Brooke E E; Stewart, Katharine E; Wright, Patricia B; McSweeney, Jean; Booth, Brenda M

    2012-01-01

    This focused ethnographic study examines data collected in 2007 from four gender- and age-specific focus groups (FGs) (N = 31) to inform the development of a sexual risk reduction intervention for African American cocaine users in rural Arkansas. A semi-structured protocol was used to guide audio-recorded FGs. Data were entered into Ethnograph and analyzed using constant comparison and content analysis. Four codes with accompanying factors emerged from the data and revealed recommendations for sexual risk reduction interventions with similar populations. Intervention design implications and challenges, study limitations, and future research are discussed. The study was supported by funds from the National Institute of Nursing Research (P20 NR009006-01) and the National Institute on Drug Abuse (1R01DA024575-01 and F31 DA026286-01).

  14. Medical consequences of cocaine.

    PubMed Central

    Gray, J. D.

    1993-01-01

    Cocaine use among middle-class North Americans increased dramatically during the 1980s. Medical complications involve almost every organ system and are produced by intense vasoconstriction. Managing cocaine-induced disease requires careful identification and the use of alpha-adrenergic blocking agents, in addition to standard therapy and referral to specialists to manage cocaine withdrawal. Images p1976-a p1980-a PMID:8106032

  15. Cocaine withdrawal in Planaria.

    PubMed

    Raffa, R B; Valdez, J M

    2001-10-26

    Cocaine-exposed planarians displayed abstinence-induced withdrawal behavior when placed into cocaine-free, but not cocaine-containing, water. The effect, manifested and quantified using a new spontaneous locomotor velocity metric, was dose-dependently related to cocaine exposure (8x10(-9) to 8x10(-5) M). Ultraviolet light (254 nm=7.83x10(-19) J), which was previously shown to interfere with drug-receptor interactions in Planaria, enhanced the abstinence-induced decreased locomotor velocity.

  16. Subtypes of Cocaine Abusers: Support for a Type A-Type B Distinction.

    ERIC Educational Resources Information Center

    Ball, Samuel A.; And Others

    1995-01-01

    Systematically assessed replicability and generalizability of a multidimensional alcoholism typological system in 399 inpatient, outpatient, and non-treatment-seeking cocaine abusers. Two different procedures supported the construct, concurrent, and predictive validity of the Type A-Type B distinction in cocaine abusers. Multidimensional…

  17. Trans-synaptic (GABA-dopamine) modulation of cocaine induced dopamine release: A potential therapeutic strategy for cocaine abuse

    SciTech Connect

    Dewey, S.L.; Straughter-Moore, R.; Chen, R.

    1995-05-01

    We recently developed a new experimental strategy for measuring interactions between functionally-linked neurotransmitter systems in the primate and human brain with PET. As part of this research, we demonstrated that increases in endogenous GABA concentrations significantly reduced striatal dopamine concentrations in the primate brain. We report here the application of the neurotransmitter interaction paradigm with PET and with microdialysis to the investigation of a novel therapeutic strategy for treating cocaine abuse based on the ability of GABA to inhibit cocaine induced increases in striatal dopamine. Using gamma-vinyl GABA (GVG, a suicide inhibitor of GABA transaminase), we performed a series of PET studies where animals received a baseline PET scan with labeled raclopride injection, animals received cocaine (2.0 mg/kg). Normally, a cocaine challenge significantly reduces the striatal binding of {sup 11}C-raclopride. However, in animals pretreated with GVG, {sup 11}C-raclopride binding was less affected by a cocaine challenge compared to control studies. Furthermore, microdialysis studies in freely moving rats demonstrate that GVG (300 mg/kg) significantly inhibited cocaine-induced increases in extracellular dopamine release. GVG also attenuated cocaine-induced increases in locomotor activity. However, at a dose of 100 mg/kg, GVG had no effect. Similar findings were obtained with alcohol. Alcohol pretreatment dose dependantly (1-4 g/kg) inhibited cocaine-induced increases in extracellular dopamine concentrations in freely moving rats. Taken together, these studies suggest that therapeutic strategies targeted at increasing central GABA concentrations may be beneficial for the treatment of cocaine abuse.

  18. The future potential for cocaine vaccines

    PubMed Central

    Orson, Frank M; Wang, Rongfu; Brimijoin, Stephen; Kinsey, Berma M; Singh, Rana AK; Ramakrishnan, Muthu; Wang, Helen Y; Kosten, Thomas R

    2014-01-01

    Introduction Addiction to cocaine is a major problem around the world, but especially in developed countries where the combination of wealth and user demand has created terrible social problems. Although only some users become truly addicted, those who are often succumb to a downward spiral in their lives from which it is very difficult to escape. From the medical perspective, the lack of effective and safe, non-addictive therapeutics has instigated efforts to develop alternative approaches for treatment, including anticocaine vaccines designed to block cocaine’s pharmacodynamic effects. Areas covered This paper discusses the implications of cocaine pharmacokinetics for robust vaccine antibody responses, the results of human vaccine clinical trials, new developments in animal models for vaccine evaluation, alternative vaccine formulations and complementary therapy to enhance anticocaine effectiveness. Expert opinion Robust anti-cocaine antibody responses are required for benefit to cocaine abusers, but since any reasonably achievable antibody level can be overcome with higher drug doses, sufficient motivation to discontinue use is also essential so that the relative barrier to cocaine effects will be appropriate for each individual. Combining a vaccine with achievable levels of an enzyme to hydrolyze cocaine to inactive metabolites, however, may substantially increase the blockade and improve treatment outcomes. PMID:24835496

  19. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  20. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  1. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  2. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  3. 21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine...

  4. Cocaine induced hippocampi infarction

    PubMed Central

    Morales Vidal, Sarkis Gibran; Hornik, Alejandro; Morgan, Christopher

    2012-01-01

    A middle age man presented with disorientation and memory impairment due to bilateral hippocampal strokes secondary to cocaine use. This is the second report of cocaine induced hippocampi ischaemic strokes. In contrast to the previous report, this middle age man did not have cardiac arrest. PMID:22761214

  5. Association of Variants in MANEA With Cocaine-Related Behaviors

    PubMed Central

    Farrer, Lindsay A.; Kranzler, Henry R.; Yu, Yi; Weiss, Roger D.; Brady, Kathleen T.; Anton, Raymond; Cubells, Joseph F.; Gelernter, Joel

    2009-01-01

    Context Cocaine dependence (CD) and related behaviors are highly heritable, but no genetic association has been consistently demonstrated. A recent genome-wide study of drug dependence identified an association between cocaine-induced paranoia (CIP) and a single-nucleotide polymorphism (SNP) in the α-endomannosidase (MANEA) locus in a family-based sample of European Americans and African Americans. Objective To conduct a comprehensive genetic association study of the MANEA locus with CD and CIP. Design Genome-wide association study. Setting Four university hospitals. Participants A total of 3992 individuals from 2 family-based and 2 case-control samples. Intervention Participants were classified as having CD or CIP or as a control using the Semi-Structured Assessment for Drug Dependence and Alcoholism. They were genotyped for 11 SNPs spanning MANEA and its surrounding region. Main Outcome Measure Association of CD and CIP with individual SNPs and haplotypes. Results Cocaine-induced paranoia was associated with 6 SNPs in the European American families and 9 SNPs in the African American families. The strongest evidence in the total sample of families was observed in 3 markers located in the promoter and 3′ untranslated regions (P < .001). The association of MANEA SNPs with CD in both family samples was much weaker. In the African American case-control sample, multiple markers were significantly associated with CIP and CD; CIP and CD were also significantly associated with a 2-SNP haplotype in the European American case-control sample. The A allele of the 3′ untranslated region SNP rs9387522 was associated with increased risk of CIP in all 4 data sets. Conclusions Our findings suggest that CD and associated behaviors may involve biological pathways not typically thought to be associated with brain metabolism. PMID:19255376

  6. [Cocaine - Characteristics and addiction].

    PubMed

    Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

    2016-01-01

    Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544. PMID:27623834

  7. [Cocaine - Characteristics and addiction].

    PubMed

    Girczys-Połedniok, Katarzyna; Pudlo, Robert; Jarząb, Magdalena; Szymlak, Agnieszka

    2016-01-01

    Cocaine use leads to health, social and legal problems. The aim of this paper is to discuss cocaine action, addicts characteristics, use patterns and consequences, as well as addiction treatment methods. A literature review was based on the Medline, PubMed, Polish Medical Bibliography databases and the Silesian Library resources. The Police and Central Statistical Office statistics, as well as the World Health Organization, the European Monitoring Centre for Drugs and Drug Addiction and the National Office for Combating Drug Addiction reports were used. Cocaine leads to mood improvement, appetite decrease, physical and intellectual activity enhancement, euphoria, inflated self-esteem, social networking ease and increased sexual desire. Cocaine hydrochloride is mainly used intranasaly, but also as intravenous and subcutaneous injections. Cocaine use and first addiction treatment fall in later age compared to other psychoactive substances. There is a high men to women ratio among addicts. There is a relationship between cocaine addiction, the presence of other disorders and genetic predisposition to addiction development. Polish reports indicate higher popularity of cocaine among people with a high economic and social status. Although Poland is a country with the low percentage of cocaine use, its popularity is growing. The consequences of cocaine use concern somatic and mental health problems, socioeconomic and legal conditions. The drug plays a role in crimes and traffic accidents. Because of the risks associated with cocaine use, it has been listed in a register of drugs attached to the Act on Counteracting Drug Addiction. Addiction treatment includes psychological, pharmacological and harm reduction strategies. Med Pr 2016;67(4):537-544.

  8. Sex Differences in Psychiatric Comorbidity and Plasma Biomarkers for Cocaine Addiction in Abstinent Cocaine-Addicted Subjects in Outpatient Settings

    PubMed Central

    Pedraz, María; Araos, Pedro; García-Marchena, Nuria; Serrano, Antonia; Romero-Sanchiz, Pablo; Suárez, Juan; Castilla-Ortega, Estela; Mayoral-Cleries, Fermín; Ruiz, Juan Jesús; Pastor, Antoni; Barrios, Vicente; Chowen, Julie A.; Argente, Jesús; Torrens, Marta; de la Torre, Rafael; Rodríguez De Fonseca, Fernando; Pavón, Francisco Javier

    2015-01-01

    effect on POEA and N-arachidonoyl-ethanolamine concentrations. Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (i.e., mood, anxiety, and psychosis disorders). Additionally, cocaine-addicted subjects showed a relationship between the concentrations of N-stearoyl-ethanolamine and 2-linoleoyl-glycerol and diagnosis of psychiatric comorbidity. These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of comorbid psychopathologies for clinical purposes. PMID:25762940

  9. Sex differences in psychiatric comorbidity and plasma biomarkers for cocaine addiction in abstinent cocaine-addicted subjects in outpatient settings.

    PubMed

    Pedraz, María; Araos, Pedro; García-Marchena, Nuria; Serrano, Antonia; Romero-Sanchiz, Pablo; Suárez, Juan; Castilla-Ortega, Estela; Mayoral-Cleries, Fermín; Ruiz, Juan Jesús; Pastor, Antoni; Barrios, Vicente; Chowen, Julie A; Argente, Jesús; Torrens, Marta; de la Torre, Rafael; Rodríguez De Fonseca, Fernando; Pavón, Francisco Javier

    2015-01-01

    effect on POEA and N-arachidonoyl-ethanolamine concentrations. Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (i.e., mood, anxiety, and psychosis disorders). Additionally, cocaine-addicted subjects showed a relationship between the concentrations of N-stearoyl-ethanolamine and 2-linoleoyl-glycerol and diagnosis of psychiatric comorbidity. These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of comorbid psychopathologies for clinical purposes.

  10. Design Case Summary. Production of Mixed Alcohols from Municipal Solid Waste via Gasification

    SciTech Connect

    Valkenburg, C.; Zhu, Y.; Walton, C. W.; Thompson, B. L.; Gerber, M. A.; Jones, S. B.; Stevens, D. J.

    2010-03-01

    The Biomass Program develops design cases to understand the current state of conversion technologies and to determine where improvements need to take place in the future. This design case establishes cost targets for converting MSW to ethanol and other mixed alcohols via gasification.

  11. Pharmacodynamic evaluation of the cardiovascular effects after the coadministration of cocaine and ethanol.

    PubMed

    Laizure, S Casey; Parker, Robert B

    2009-02-01

    One of the most common drug dependencies occurring with alcoholism is cocaine dependence. This combination is particularly worrisome because of the increased risk of cardiovascular events associated with their coabuse. Although it is well known that ethanol increases the cardiovascular effects of cocaine by inhibiting cocaine clearance and the formation of cocaethylene, it has also been postulated that ethanol enhances the cardiovascular effects of cocaine independent of the two latter mechanisms. In this study, we investigated the cardiovascular pharmacodynamics of the cocaine-ethanol interaction to determine whether ethanol directly enhanced the cardiovascular effects of cocaine. Dogs (n = 6) were administered cocaine alone (3 mg/kg i.v.) and in combination with ethanol (1 g/kg i.v.) on separate study days. Blood pressure, heart rate, and the electrocardiogram were monitored continuously, and blood samples were collected periodically after drug administration. Concentration-time data were fitted to a two-compartment model, and concentration-effect data were fitted to a simple E(max) model using WinNonlin software. Pharmacokinetic and pharmacodynamic parameters were compared between the two treatment phases by a paired t test. The administration of ethanol before cocaine resulted in a decrease in cocaine clearance, but there were no differences in any of the other pharmacokinetic or pharmacodynamic parameter values between the cocaine alone and cocaine plus ethanol phases. As has been demonstrated in previous animal and human studies, the clearance of cocaine was decreased by prior administration of ethanol. However, ethanol did not change the concentration-effect relationship of the cardiovascular response to cocaine administration. It is concluded from this study that ethanol does not directly enhance the cardiovascular effects of cocaine. PMID:19005030

  12. Hairpin Ribozyme Genes Curtail Alcohol Drinking: from Rational Design to in vivo Effects in the Rat.

    PubMed

    Sapag, Amalia; Irrazábal, Thergiory; Lobos-González, Lorena; Muñoz-Brauning, Carlos R; Quintanilla, María Elena; Tampier, Lutske

    2016-01-01

    Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of alcohol dependence. Acetaldehyde generated from alcohol in the liver is metabolized by the mitochondrial aldehyde dehydrogenase (ALDH2) such that diminishing ALDH2 activity leads to the aversive effects of blood acetaldehyde upon alcohol intake. A stepwise approach was followed to design genes encoding ribozymes targeted to the rat ALDH2 mRNA. In vitro studies of accessibility to oligonucleotides identified suitable target sites in the mRNA, one of which fulfilled hammerhead and hairpin ribozyme requirements (CGGUC). Ribozyme genes delivered in plasmid constructs were tested in rat cells in culture. While the hairpin ribozyme reduced ALDH2 activity 56% by cleavage and blockade (P < 0.0001), the hammerhead ribozyme elicited minor effects by blockade. The hairpin ribozyme was tested in vivo by adenoviral gene delivery to UChB alcohol drinker rats. Ethanol intake was curtailed 47% for 34 days (P < 0.0001), while blood acetaldehyde more than doubled upon ethanol administration and ALDH2 activity dropped 25% in liver homogenates, not affecting other ALDH isoforms. Thus, hairpin ribozymes targeted to 16 nt in the ALDH2 mRNA provide durable and specific effects in vivo, representing an improvement on previous work and encouraging development of gene therapy for alcoholism. PMID:27404720

  13. Hairpin Ribozyme Genes Curtail Alcohol Drinking: from Rational Design to in vivo Effects in the Rat.

    PubMed

    Sapag, Amalia; Irrazábal, Thergiory; Lobos-González, Lorena; Muñoz-Brauning, Carlos R; Quintanilla, María Elena; Tampier, Lutske

    2016-07-12

    Ribozyme genes were designed to reduce voluntary alcohol drinking in a rat model of alcohol dependence. Acetaldehyde generated from alcohol in the liver is metabolized by the mitochondrial aldehyde dehydrogenase (ALDH2) such that diminishing ALDH2 activity leads to the aversive effects of blood acetaldehyde upon alcohol intake. A stepwise approach was followed to design genes encoding ribozymes targeted to the rat ALDH2 mRNA. In vitro studies of accessibility to oligonucleotides identified suitable target sites in the mRNA, one of which fulfilled hammerhead and hairpin ribozyme requirements (CGGUC). Ribozyme genes delivered in plasmid constructs were tested in rat cells in culture. While the hairpin ribozyme reduced ALDH2 activity 56% by cleavage and blockade (P < 0.0001), the hammerhead ribozyme elicited minor effects by blockade. The hairpin ribozyme was tested in vivo by adenoviral gene delivery to UChB alcohol drinker rats. Ethanol intake was curtailed 47% for 34 days (P < 0.0001), while blood acetaldehyde more than doubled upon ethanol administration and ALDH2 activity dropped 25% in liver homogenates, not affecting other ALDH isoforms. Thus, hairpin ribozymes targeted to 16 nt in the ALDH2 mRNA provide durable and specific effects in vivo, representing an improvement on previous work and encouraging development of gene therapy for alcoholism.

  14. Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats

    PubMed Central

    Schmoutz, Christopher D; Zhang, Yanan; Runyon, Scott P; Goeders, Nicholas E

    2012-01-01

    Neuropeptide S (NPS) is a neuromodulatory peptide, acting via a G-protein-coupled receptor to regulate sleep, anxiety and behavioral arousal. Recent research has found that intracerebroventricular NPS can increase cocaine and alcohol self-administration in rodents, suggesting a key role in reward-related neurocircuitry. It is hypothesized that antagonism of the NPS system might represent a novel strategy for the pharmacological treatment of cocaine abuse. To this end, a small-molecule NPSR antagonist (RTI-118) was developed and tested in animal models of cocaine seeking and cocaine taking. Male Wistar rats (n=54) trained to self-administer cocaine and food under a concurrent alternating FR4 schedule exhibited specific dose-dependent decreases in cocaine intake when administered RTI-118. RTI-118 also decreased the reinstatement of extinguished cocaine-seeking behavior induced by conditioned cues, yohimbine and a priming dose of cocaine. These data support the hypothesis that antagonism of the neuropeptide S receptor may ultimately show efficacy in reducing cocaine use and relapse. PMID:22982682

  15. Cocaine use and stroke

    PubMed Central

    Treadwell, Sean D; Robinson, Tom G

    2007-01-01

    Stroke is the third most common cause of death in developed countries. In England and Wales, 1000 people under the age of 30 have a stroke each year. Cocaine is the most commonly used class A drug, and the first report of cocaine‐induced stroke was in 1977. Since the development of alkaloidal “crack” cocaine in the 1980s, there has been a significant rise in the number of case reports describing both ischaemic and haemorrhagic stroke associated with cocaine use. Cocaine is a potent central nervous system stimulant, and acts by binding to specific receptors at pre‐synaptic sites preventing the reuptake of neurotransmitters. The exact mechanism of cocaine‐induced stroke remains unclear and there are likely to be a number of factors involved including vasospasm, cerebral vasculitis, enhanced platelet aggregation, cardioembolism, and hypertensive surges associated with altered cerebral autoregulation. The evidence surrounding each of these factors will be considered here. PMID:17551070

  16. Cocaine and Pregnancy

    MedlinePlus

    ... the semen and may reduce the number of sperm, and increase the number of abnormal sperm. This can result in fertility problems. Cocaine can attach to sperm. This has led to the suggestion that sperm ...

  17. Phenytoin Toxicity from Cocaine Adulteration

    PubMed Central

    Roldan, Carlos J.

    2014-01-01

    The use of phenytoin (PHT) as a cocaine adulterant was reported decades ago; that practice is still current. Ironically PHT has also been used for the treatment of cocaine dependence. A drug smuggler developed PHT toxicity after swallowing several rocks of crack. We investigated the current trends of PHT as a cocaine adulterant and its toxicological implications. We also reviewed the clinical use of PTH in relation to cocaine. The use of PHT as cocaine cut is a current practice. This may affect the clinical manifestations and the management of the cocaine-related visits to the emergency department. PMID:24672596

  18. Prenatal Cocaine Exposures and Dose-Related Cocaine Effects on Infant Tone and Behavior

    PubMed Central

    Chiriboga, Claudia A.; Kuhn, Louise; Wasserman, Gail A.

    2015-01-01

    Background In experimental models, prenatal cocaine exposure has been found to perturb monoaminergic development. In humans, numerous studies have sought clinical correlates, but few have focused on dose-related effects, especially as regards neurologic function beyond the neonatal period. Objective To assess whether prenatal cocaine exposure has adverse effects on infant neurologic, developmental and behavioral outcomes and whether any effects are dose-dependent. Design/Methods Infants (398) were enrolled at birth from an urban hospital. Drug exposure was ascertained with biomarkers in hair (n=395), urine (n=170) and meconium (n=109). Children were followed prospectively and 286 (72%) were evaluated blind to drug exposure at 6 months of age with the Bayley scales, Fagan Scale of Infant Intelligence and a standardized neurological examination. Results Certain neurological findings increased significantly by the amount of cocaine detected in maternal hair, e.g. abnormality of tone, as indicated by extensor posture was detected among 28% of cocaine-unexposed infants, 43% of infants exposed to lower and 48% exposed to higher cocaine levels in maternal hair (p<0.009). Persistent fisting increased in a similar dose-dependent manner. These associations persisted in adjusted analyses. Prenatal cocaine exposure was not associated with developmental scores (mental, motor or novelty preference) but was associated with lower orientation scores in adjusted analyses. Conclusions At 6 months of age, prenatal cocaine exposure was associated with abnormalities of tone and posture and with lower orientation scores. Perturbations in monoaminergic systems by cocaine exposure during fetal development may explain the observed neurological and behavioral symptoms. Whether such findings in infancy increase the risk of later neurobehavioral problems requires further study. PMID:17234383

  19. A Study of Alcohol Use by Designated Drivers among College Students

    ERIC Educational Resources Information Center

    Dermody, Sarah S.; Cheong, JeeWon; Walther, Christine A.

    2012-01-01

    Objective: College students tend to drink while serving as a designated driver (DD). The predictors of alcohol use by DDs among college students were examined. Participants: Participants were 119 undergraduate students in introductory psychology courses who had experience with DD use. Methods: Survey data were analyzed to examine the predictors of…

  20. Cocaine Babies: Florida's Substance-Exposed Youth.

    ERIC Educational Resources Information Center

    Harpring, Jayme

    This report is designed to provide Florida's school personnel with assistance in working with students prenatally exposed to cocaine or other toxic substances. The report offers background data, practical strategies for teaching and learning, and resources for networking. The first chapter outlines statistics on the incidence of the problem of…

  1. Recommendations for the Design and Analysis of Treatment Trials for Alcohol Use Disorders

    PubMed Central

    Witkiewitz, Katie; Finney, John W.; Harris, Alex H.S; Kivlahan, Daniel R.; Kranzler, Henry R.

    2015-01-01

    Background Over the past 60 years the view that “alcoholism” is a disease for which the only acceptable goal of treatment is abstinence has given way to the recognition that alcohol use disorders (AUDs) occur on a continuum of severity, for which a variety of treatment options are appropriate. However, because the available treatments for AUDs are not effective for everyone, more research is needed to develop novel and more efficacious treatments to address the range of AUD severity in diverse populations. Here we offer recommendations for the design and analysis of alcohol treatment trials, with a specific focus on the careful conduct of randomized clinical trials of medications and non-pharmacological interventions for AUDs. Methods Narrative review of the quality of published clinical trials and recommendations for the optimal design and analysis of treatment trials for AUDs. Results Despite considerable improvements in the design of alcohol clinical trials over the past two decades, many studies of AUD treatments have used faulty design features and statistical methods that are known to produce biased estimates of treatment efficacy. Conclusions The published statistical and methodological literatures provide clear guidance on methods to improve clinical trial design and analysis. Consistent use of state-of-the-art design features and analytic approaches will enhance the internal and external validity of treatment trials for AUDs across the spectrum of severity. The ultimate result of this attention to methodological rigor is that better treatment options will be identified for patients with an AUD. PMID:26250333

  2. Cocaine abuse during pregnancy.

    PubMed

    Cressman, Alex M; Natekar, Aniket; Kim, Eunji; Koren, Gideon; Bozzo, Pina

    2014-07-01

    Cocaine abuse during pregnancy is a significant public health problem but is infrequently discussed between physicians and patients. The impact of in utero cocaine exposure on pregnancy and the baby has received significant media attention in preceding decades because of fears of teratogenicity, long-term health consequences, and poor cognitive and neurodevelopmental outcomes. We sought to review the medical literature examining these phenomena. We identified risks to the pregnancy and baby in women abusing cocaine during pregnancy. These include preterm birth, placenta-associated syndromes (e.g., placental abruption, preeclampsia, and placental infarction), and impaired fetal growth. Long-term neurodevelopmental and cognitive deficits include (but are not limited to) poorer language development, learning and perceptual reasoning, behavioural problems, and adverse effects on memory and executive function. However, these results should be interpreted cautiously because cocaine abuse may be accompanied by many other maternal and sociodemographic risk factors, so it is difficult to ascertain the effect of cocaine alone. Therefore, it is critical to counsel patients about potential risk, and perhaps more importantly, to treat addiction and to better understand, and advocate for improvements to, these patients' high-risk environment.

  3. Vaccines against stimulants: cocaine and MA

    PubMed Central

    Kosten, Thomas; Domingo, Coreen; Orson, Frank; Kinsey, Berma

    2014-01-01

    While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014. PMID:23509915

  4. Early adolescent cocaine use as determined by hair analysis in a prenatal cocaine exposure cohort

    PubMed Central

    Warner, Tamara Duckworth; Behnke, Marylou; Eyler, Fonda Davis; Szabo, Nancy J.

    2010-01-01

    Background Preclinical and other research suggest that youth with prenatal cocaine exposure (PCE) may be at high risk for cocaine use due to both altered brain development and exposure to unhealthy environments. Methods Participants are early adolescents who were prospectively enrolled in a longitudinal study of PCE prior to or at birth. Hair samples were collected from the youth at ages 10½ and 12½ (N=263). Samples were analyzed for cocaine and its metabolites using ELISA screening with gas chromatography/mass spectroscopy (GC/MS) confirmation of positive samples. Statistical analyses included comparisons between the hair-positive and hair-negative groups on risk and protective factors chosen a priori as well as hierarchical logistical regression analyses to predict membership in the hair-positive group. Results Hair samples were positive for cocaine use for 14% (n=36) of the tested cohort. Exactly half of the hair-positive preteens had a history of PCE. Group comparisons revealed that hair-negative youth had significantly higher IQ scores at age 10½; the hair-positive youth had greater availability of cigarettes, alcohol, and other drugs in the home; caregivers with more alcohol problems and depressive symptoms; less nurturing home environments; and less positive attachment to their primary caregivers and peers. The caregivers of the hair-positive preteens reported that the youth displayed more externalizing and social problems, and the hair-positive youth endorsed more experimentation with cigarettes, alcohol, and/or other drugs. Mental health problems, peer drug use, exposure to violence, and neighborhood characteristics did not differ between the groups. Regression analyses showed that the availability of drugs in the home had the greatest predictive value for hair-positive group membership while higher IQ, more nurturing home environments, and positive attachment to caregivers or peers exerted some protective effect. Conclusion The results do not support a

  5. Fluorescence Immunoassay for Cocaine Detection.

    PubMed

    Nakayama, Hiroshi; Kenjjou, Noriko; Shigetoh, Nobuyuki; Ito, Yuji

    2016-04-01

    A fluorescence immunoassay (FIA) has been developed for the detection of cocaine using norcocaine labeled with merocyanine dye and a monoclonal antibody specific to cocaine. Using this FIA, the detection range for cocaine was between 20.0 and 1700 μg/L with a limit of detection of 20.0 μg/L. Other cocaine derivatives did not interfere significantly with the detection when using this immunoassay technique with cross-reactivity values of less than 20%. Thus this FIA could be considered a useful tool for the detection of cocaine.

  6. Fluorescence Immunoassay for Cocaine Detection.

    PubMed

    Nakayama, Hiroshi; Kenjjou, Noriko; Shigetoh, Nobuyuki; Ito, Yuji

    2016-04-01

    A fluorescence immunoassay (FIA) has been developed for the detection of cocaine using norcocaine labeled with merocyanine dye and a monoclonal antibody specific to cocaine. Using this FIA, the detection range for cocaine was between 20.0 and 1700 μg/L with a limit of detection of 20.0 μg/L. Other cocaine derivatives did not interfere significantly with the detection when using this immunoassay technique with cross-reactivity values of less than 20%. Thus this FIA could be considered a useful tool for the detection of cocaine. PMID:26977890

  7. Cocaine detection using piezoresistive microcantilevers

    NASA Astrophysics Data System (ADS)

    Srijanto, Bernadeta; Cheney, Christine P.; Hedden, David L.; Gehl, Anthony; Ferrell, Thomas L.

    2008-03-01

    Sensitive and inexpensive sensors play a significant role in the analysis of drugs and drug metabolites. Specifically, reliable in vivo detection of cocaine and cocaine metabolites serves as a useful tool in research of the body's reaction to the drug and in the treatment of the drug addiction. We present here a promising cocaine biosensor to be used in the human body. The sensor's active element consists of piezoresistive microcantilevers coated with an oligonucleotide-based aptamer as the cocaine binder. In vitro cocaine detection was carried out by flowing a cocaine solution over the microcantilevers. Advantages of this device are its low power consumption, its high sensitivity, and its potential for miniaturization into an implantable capsule. The limit of detection for cocaine in distilled water was found to be 1 ng/ml.

  8. Benzodiazepine inhibits anxiogenic-like response in cocaine or ethanol withdrawn planarians.

    PubMed

    Nayak, Sunil; Roberts, Adam; Bires, Kristofer; Tallarida, Christopher S; Kim, Erin; Wu, Michael; Rawls, Scott M

    2016-09-01

    Planarians spend less time in light versus dark environments. We hypothesized that planarians withdrawn from cocaine or ethanol would spend even less time in the light than drug-naive planarians and that a benzodiazepine would inhibit this response. Planarians pretreated in cocaine or ethanol were placed at the midline of a Petri dish containing spring water that was split evenly into dark and light compartments. Planarians withdrawn from cocaine (1, 10, 100 μmol/l) or ethanol (0.01%) spent less time in the light compartment than water controls; however, this withdrawal response to cocaine (100 μmol/l) or ethanol (0.01%) was abolished by clorazepate (0-100 μmol/l). These data suggest that planarians, similar to rodents, show benzodiazepine-sensitive, anxiogenic-like responses during cocaine or alcohol withdrawal.

  9. Quinine enhances the behavioral stimulant effect of cocaine in mice.

    PubMed

    Huertas, Adriana; Wessinger, William D; Kucheryavykh, Yuri V; Sanabria, Priscila; Eaton, Misty J; Skatchkov, Serguei N; Rojas, Legier V; Maldonado-Martínez, Gerónimo; Inyushin, Mikhail Y

    2015-02-01

    The Na(+)-dependent dopamine transporter (DAT) is primarily responsible for regulating free dopamine (DA) concentrations in the brain by participating in the majority of DA uptake; however, other DA transporters may also participate, especially if cocaine or other drugs of abuse compromise DAT. Recently, such cocaine-insensitive low-affinity mono- and poly-amine OCT transporters were described in astrocytes which use DA as a substrate. These transporters are from a different transporter family and while insensitive to cocaine, they are specifically blocked by quinine and some steroids. Quinine is inexpensive and is often found in injected street drugs as an "adulterant". The present study was designed to determine the participation of OCTs in cocaine dependent behavioral and physiological changes in mice. Using FVB mice we showed, that daily single injections of quinine (10 mg/kg, i.p.) co-administered with cocaine (15 mg/kg, i.p.) for 10 days significantly enhanced cocaine-induced locomotor behavioral sensitization. Quinine had no significant effect on the time course of behavioral activation. In astrocytes from the ventral tegmental area of mice, transporter currents of quinine-sensitive monoamine transporters were also augmented after two weeks of cocaine administration. The importance of low-affinity high-capacity transporters for DA clearance is discussed, explaining the known ability of systemically administered DAT inhibitors to anomalously increase DA clearance.

  10. The role of designated driver programs in the prevention of alcohol-impaired driving: a critical reassessment.

    PubMed

    DeJong, W; Wallack, L

    1992-01-01

    We review the "designated driver" concept and the current debate over its role in preventing alcohol-impaired driving. In our view, the focus on this strategy by broadcasters, the alcohol industry, and various public service groups has deflected attention from other alcohol-related problems that account for the vast majority of deaths and injuries associated with alcohol use. This focus has also distracted many public health advocates and policymakers from the bigger and more important jobs of increasing public awareness of the social, environmental, and economic factors that influence alcohol consumption and promoting debate on legislation and other public policy solutions to alcohol-impaired driving. As part of a comprehensive strategy, we strongly encourage a renewed focus on "sobriety checkpoints," strict enforcement of laws against alcohol sales to minors, alcohol advertising reform, increased excise taxes, and other public policy initiatives supported by the Surgeon General. These measures will curb underage and heavy alcohol consumption and will create a legal and social environment in which individuals are motivated to avoid impaired driving through several alternative strategies, including but not limited to the use of designated drivers.

  11. Nociceptin receptor activation does not alter acquisition, expression, extinction and reinstatement of conditioned cocaine preference in mice.

    PubMed

    Sartor, G C; Powell, S K; Wiedner, H J; Wahlestedt, C; Brothers, S P

    2016-02-01

    Growing evidence indicates that targeting nociceptin receptor (NOP) signaling may have therapeutic efficacy in treating alcohol and opioid addiction. However, little is known about the therapeutic value of selective NOP agonists for the treatment of cocaine dependence. Recently, we identified a highly selective, brain-penetrant NOP small molecule agonist (SR-8993), and using this compound, we previously showed that nociceptin receptor activation attenuated consolidation of fear-related memories. Here, we sought to determine whether SR-8993 also affects the rewarding properties of cocaine. Using a conditioned place preference (CPP) procedure, we show that SR-8993 (3 or 10 mg/kg) failed to disrupt acquisition or expression of cocaine CPP (7.5 or 15 mg/kg) in C57BL/6 mice. Additionally, SR-8993 did not affect rate of extinction or reinstatement (yohimbine- and cocaine-induced) of cocaine CPP. These studies indicate that selective activation of NOP may not be sufficient in reducing behavioral responses to cocaine.

  12. A culturally-tailored behavioral intervention trial for alcohol use disorders in three American Indian communities: Rationale, design, and methods

    PubMed Central

    McDonell, Michael G.; Nepom, Jenny R.; Leickly, Emily; Suchy-Dicey, Astrid; Hirchak, Kait; Echo-Hawk, Abigail; Schwartz, Stephen M.; Calhoun, Darren; Donovan, Dennis; Roll, John; Ries, Richard; Buchwald, Dedra

    2016-01-01

    Background Disproportionately high rates of alcohol use disorders are present in many American Indian/Alaska Native (AI/AN) communities, yet little information exists regarding the effectiveness of alcohol treatments in AI/AN populations. Contingency management is an intervention for illicit drug use in which tangible reinforcers (rewards) are provided when patients demonstrate abstinence as assessed by urine drug tests. Contingency management has not been widely studied as an intervention for alcohol problems because until recently, no alcohol biomarker has been available to adequately verify abstinence. Aims The HONOR Study is designed to determine whether a culturally-tailored contingency management intervention is an effective intervention for AI/AN adults who suffer from alcohol use disorders. Methods Participants include 400 AI/AN alcohol-dependent adults residing in one rural reservation, one urban community, as well as a third site to be decided, in the Western U.S. Participants complete a 4-week lead-in phase prior to randomization, then 12 weeks of either a contingency management intervention for alcohol abstinence, or a control condition where participants receive reinforcers for attending study visits regardless of alcohol use. Participants are then followed for 3-more months post-intervention. The primary study outcome is urinary ethyl glucuronide-confirmed alcohol abstinence; secondary outcomes include self-reported alcohol and drug use, HIV risk behaviors, and self-reported cigarette smoking. Discussion This will be the largest randomized, controlled trial of any alcohol for AI/ANs and the largest contingency management study targeting alcohol use disorders, thus providing important information to AI/AN communities and the alcohol treatment field in general. PMID:26706667

  13. Combined Cocaine Hydrolase Gene Transfer and Anti-Cocaine Vaccine Synergistically Block Cocaine-Induced Locomotion

    PubMed Central

    Carroll, Marilyn E.; Zlebnik, Natalie E.; Anker, Justin J.; Kosten, Thomas R.; Orson, Frank M.; Shen, Xiaoyun; Kinsey, Berma; Parks, Robin J.; Gao, Yang; Brimijoin, Stephen

    2012-01-01

    Mice and rats were tested for reduced sensitivity to cocaine-induced hyper-locomotion after pretreatment with anti-cocaine antibody or cocaine hydrolase (CocH) derived from human butyrylcholinesterase (BChE). In Balb/c mice, direct i.p. injection of CocH protein (1 mg/kg) had no effect on spontaneous locomotion, but it suppressed responses to i.p. cocaine up to 80 mg/kg. When CocH was injected i.p. along with a murine cocaine antiserum that also did not affect spontaneous locomotion, there was no response to any cocaine dose. This suppression of locomotor activity required active enzyme, as it was lost after pretreatment with iso-OMPA, a selective BChE inhibitor. Comparable results were obtained in rats that developed high levels of CocH by gene transfer with helper-dependent adenoviral vector, and/or high levels of anti-cocaine antibody by vaccination with norcocaine hapten conjugated to keyhole limpet hemocyanin (KLH). After these treatments, rats were subjected to a locomotor sensitization paradigm involving a “training phase" with an initial i.p. saline injection on day 1 followed by 8 days of repeated cocaine injections (10 mg/kg, i.p.). A 15-day rest period then ensued, followed by a final “challenge" cocaine injection. As in mice, the individual treatment interventions reduced cocaine-stimulated hyperactivity to a modest extent, while combined treatment produced a greater reduction during all phases of testing compared to control rats (with only saline pretreatment). Overall, the present results strongly support the view that anti-cocaine vaccine and cocaine hydrolase vector treatments together provide enhanced protection against the stimulatory actions of cocaine in rodents. A similar combination therapy in human cocaine users might provide a robust therapy to help maintain abstinence. PMID:22912888

  14. Emotion recognition during cocaine intoxication.

    PubMed

    Kuypers, K P C; Steenbergen, L; Theunissen, E L; Toennes, S W; Ramaekers, J G

    2015-11-01

    Chronic or repeated cocaine use has been linked to impairments in social skills. It is not clear whether cocaine is responsible for this impairment or whether other factors, like polydrug use, distort the observed relation. We aimed to investigate this relation by means of a placebo-controlled experimental study. Additionally, associations between stressor-related activity (cortisol, cardiovascular parameters) induced by the biological stressor cocaine, and potential cocaine effects on emotion recognition were studied. Twenty-four healthy recreational cocaine users participated in this placebo-controlled within-subject study. Participants were tested between 1 and 2 h after treatment with oral cocaine (300 mg) or placebo. Emotion recognition of low and high intensity expressions of basic emotions (fear, anger, disgust, sadness, and happiness) was tested. Findings show that cocaine impaired recognition of negative emotions; this was mediated by the intensity of the presented emotions. When high intensity expressions of Anger and Disgust were shown, performance under influence of cocaine 'normalized' to placebo-like levels while it made identification of Sadness more difficult. The normalization of performance was most notable for participants with the largest cortisol responses in the cocaine condition compared to placebo. It was demonstrated that cocaine impairs recognition of negative emotions, depending on the intensity of emotion expression and cortisol response. PMID:26328908

  15. Emotion recognition during cocaine intoxication.

    PubMed

    Kuypers, K P C; Steenbergen, L; Theunissen, E L; Toennes, S W; Ramaekers, J G

    2015-11-01

    Chronic or repeated cocaine use has been linked to impairments in social skills. It is not clear whether cocaine is responsible for this impairment or whether other factors, like polydrug use, distort the observed relation. We aimed to investigate this relation by means of a placebo-controlled experimental study. Additionally, associations between stressor-related activity (cortisol, cardiovascular parameters) induced by the biological stressor cocaine, and potential cocaine effects on emotion recognition were studied. Twenty-four healthy recreational cocaine users participated in this placebo-controlled within-subject study. Participants were tested between 1 and 2 h after treatment with oral cocaine (300 mg) or placebo. Emotion recognition of low and high intensity expressions of basic emotions (fear, anger, disgust, sadness, and happiness) was tested. Findings show that cocaine impaired recognition of negative emotions; this was mediated by the intensity of the presented emotions. When high intensity expressions of Anger and Disgust were shown, performance under influence of cocaine 'normalized' to placebo-like levels while it made identification of Sadness more difficult. The normalization of performance was most notable for participants with the largest cortisol responses in the cocaine condition compared to placebo. It was demonstrated that cocaine impairs recognition of negative emotions, depending on the intensity of emotion expression and cortisol response.

  16. The cocaine-abused heart.

    PubMed

    Keller, Kathryn Buchanan; Lemberg, Louis

    2003-11-01

    Recreational use of cocaine dates back to the Incas in South America 5000 years ago. Cocaine is derived from the leaves of Erythroxylon coca, a shrub native to South America. In the late 1800s, Sigmund Freud popularized the drug in Europe. He used cocaine to treat depression, asthma, cachexia, and for overcoming morphine addiction. Also in this period cocaine rapidly gained acceptance in surgical procedures as a local anesthetic and vasoconstrictor. Cocaine reached the United States in the early 1900s, and its popularity led President Taft to declare it public enemy number one in 1910. Cocaine became popular again in the 1980s. Currently cocaine use is responsible for more ED visits then any of the other illicit drugs. Because most cocaine users are young, they are at a lower risk for coronary artery atherosclerotic disease. An estimated 25 million people between the ages of 26 and 34 years have used cocaine at least once, 20% were women and 30% men. Habitual users of cocaine are estimated to number 1.5 million. Most cocaine-induced chest pains do not progress to MI, and in fact many originate in the chest wall. The chest pains due to cocaine, however, are induced by myocardial ischemia, a result of vasospasm and not a thrombotic occlusion of a coronary artery that has a ruptured atheromatous plaque. ECG findings can be misleading in the diagnosis because the early repolarization syndrome, a normal variant, is a frequent finding in young African American men. Measurement of cardiac troponin levels is the most reliable diagnostic test. Percutaneous coronary intervention and angioplasty, rather than thrombolysis, is the treatment of choice because intense coronary vasospasm is the primary pathophysiology in cocaine-induced MI.

  17. Signs of Cocaine Abuse and Addiction

    MedlinePlus

    ... Signs of Cocaine Use and Addiction Signs of Cocaine Use and Addiction Listen After the "high" of ... Version Download "My life was built around getting cocaine and getting high." Stacey is recovering from her ...

  18. Demographic and psychological factors associated with lifetime cocaine use: An exploratory factor analysis of baseline questionnaires

    PubMed Central

    Dias, Nadeeka R; Lane, Scott D; Rathnayaka, Nuvan; Schmitz, Joy M; Green, Charles E

    2014-01-01

    Objectives Underlying heterogeneity among individuals with cocaine dependence is widely postulated in the literature, however, identification of a group of factors that explain risk of cocaine use severity has yet to be confirmed. Methods Latent mixture modeling evaluated 338 cocaine-dependent individuals recruited from the community to assess the evidence for the presence of distinct subgroups. Variables included 5 baseline questionnaires measuring cognitive function (Shipley), impulsivity (BIS), mood (BDI), affective lability (ALS), and addiction severity (ASI). Results failed to suggest multiple subgroups. Given a lack of evidence for discrete latent classes, an exploratory factor analysis (EFA) followed by exploratory structural equation modeling (ESEM) was implemented to identify functional dimensions to enhance interpretation of these variables. Results Findings from the EFA indicated a 3-factor model as the best fit, and the subsequent ESEM solution resulted in associations with lifetime cocaine use. Factor 1, best characterized by demographic factors (gender, age), is associated with less lifetime cocaine use. Psychological problems best characterize factor 2, which is associated with higher lifetime cocaine use. Finally, factor 3 is characterized by other substance use (alcohol and marijuana). Although this factor did not demonstrate a statistically reliable relation with self-reported, lifetime cocaine use, it did indicate a potentially meaningful positive association. Conclusions These 3 factors delineate dimensions of functioning that likewise help characterize the variability found in previously established associations with self-reported cocaine use. PMID:26170765

  19. Sudden Death Due To Acute Cocaine Toxicity-Excited Delirium in a Body Packer.

    PubMed

    Shields, Lisa B E; Rolf, Cristin M; Hunsaker, John C

    2015-11-01

    Excited delirium denotes a life-threatening medical condition characterized by the acute onset of agitated and violent behavior that often results in a sudden and unexplained death. Cocaine-induced excited delirium refers to fatal cocaine intoxication with the following symptoms occurring sequentially: hyperthermia, delirium with agitation, respiratory arrest, and death. We present a case of cocaine-induced excited delirium in a cocaine "body packer" or a "mule", specifically an individual who attempts to smuggle cocaine within the body. Investigators at the scene initially suspected homicide due to the victim's sharp and blunt force injuries. Three rubber packets containing cocaine were removed from the victim's rectum. Blood toxicological analysis revealed an alcohol concentration of 0.016 g/100 and cocaine >1 mg/L. The forensic pathologist should consider cocaine-induced excited delirium when an individual exhibits aggressive behavior, unexpected strength, and resistance to pain who dies suddenly. Further analysis should be performed during the scene investigation and autopsy for evidence of body packing.

  20. Prolonged attenuation of the reinforcing strength of cocaine by chronic d-amphetamine in rhesus monkeys.

    PubMed

    Czoty, Paul W; Gould, Robert W; Martelle, Jennifer L; Nader, Michael A

    2011-01-01

    Chronic treatment with the indirect dopamine agonist d-amphetamine can reduce cocaine use in clinical trials and, in preclinical studies in laboratory animals, attenuates daily cocaine self-administration. The present study extended previous results to conditions designed to reflect a more clinically relevant experience of cocaine exposure and d-amphetamine treatment. Each morning, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio schedule of reinforcement. After determining a dose-response curve for cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule of reinforcement in the evening, cocaine self-administration sessions were suspended and d-amphetamine (0.01-0.056 mg/kg/h, i.v.) was administered continuously for at least 24 days, except during cocaine self-administration sessions, which were conducted using the PR schedule once every 8 days. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was redetermined. Cocaine- and food-maintained responding were also examined after discontinuation of d-amphetamine. Although individual differences in sensitivity were observed, d-amphetamine produced selective, qualitatively similar decreases in the reinforcing strength of cocaine in all monkeys that persisted at least 4 weeks. Moreover, cocaine dose-effect curves were shifted downward and/or to the right. For 2 weeks following discontinuation of d-amphetamine treatment, the reinforcing strength of cocaine varied within and across individuals, however, on the whole no increased sensitivity was apparent. These data provide further support for the use of agonist medications for cocaine abuse, and extend the conditions under which such treatment is successful to those that incorporate clinically relevant patterns of cocaine use and drug treatment. PMID:20962765

  1. The Role of Designated Driver Programs in the Prevention of Alcohol-Impaired Driving: A Critical Reassessment [and] Designated Driver Programs: A Commentary on the DeJong and Wallack Article.

    ERIC Educational Resources Information Center

    DeJong, William; And Others

    1992-01-01

    Focus on the designated driver strategy by broadcasters and the alcohol industry deflects attention from other alcohol-related problems and the factors influencing underage alcohol consumption. Strategies should emphasize sobriety checkpoints, no sales to minors, advertising reform, and excise taxes on alcohol. (SK)

  2. PET Studies in Nonhuman Primate Models of Cocaine Abuse: Translational Research Related to Vulnerability and Neuroadaptations

    PubMed Central

    Gould, Robert W.; Duke, Angela N.; Nader, Michael A.

    2013-01-01

    The current review highlights the utility of positron emission tomography (PET) imaging to study the neurobiological substrates underlying vulnerability to cocaine addiction and subsequent adaptations following chronic cocaine self-administration in nonhuman primate models of cocaine abuse. Environmental (e.g., social rank) and sex-specific influences on dopaminergic function and sensitivity to the reinforcing effects of cocaine are discussed. Cocaine-related cognitive deficits have been hypothesized to contribute to high rates of relapse and are described in nonhuman primate models. Lastly, the long-term consequences of cocaine on neurobiology are discussed. PET imaging and longitudinal, within-subject behavioral studies in nonhuman primates have provided a strong framework for designing pharmacological and behavioral treatment strategies to aid drug-dependent treatment seekers. Non-invasive PET imaging will allow for individualized treatment strategies. Recent advances in radiochemistry of novel PET ligands and other imaging modalities can further advance our understanding of stimulant use on the brain. PMID:23458573

  3. Determination of fatty acid ethyl esters in hair by GC-MS and application in a population of cocaine users.

    PubMed

    Politi, Lucia; Mari, Francesco; Furlanetto, Sandra; Del Bravo, Ester; Bertol, Elisabetta

    2011-04-01

    A gas chromatography-mass spectrometry method for the determination of ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate in hair samples was developed, validated and applied to real samples. Ethyl myristate, ethyl palmitate, ethyl oleate, and ethyl stearate are fatty acid ethyl esters (FAEE) which are known to be direct biotransformation products of ethanol. Their presence in the body fluids and tissue is therefore indicative of alcohol intake and, in particular, FAEE concentration in hair higher than 0.5 ng/mg is indicative of excessive chronic alcohol consumption. The method was applied to 80 hair samples formerly found positive for cocaine and FAEE analytical results were compared with the presence of cocaethylene, a cocaine metabolite formed only when alcohol and cocaine are used together. According to our data the two biomarkers (FAEE and cocaethylene in hair) are tools of great value in the assessment of the diagnosis of use of cocaine and ethanol. In fact, discrepancies were noted and might be related to various factors including differences in consumption habits and thus permitting to distinguish the use of both substances non-concurrently or concurrently. Also, the determination of both markers may, in some cases, discriminate the use of moderate or heavy alcohol amounts when associated with cocaine. Finally, in a population of non-cocaine-users our results support FAEE as valuable means in the assessment of excessive alcohol chronic use. PMID:21159458

  4. Gender Differences in Alcohol and Polysubstance Users.

    ERIC Educational Resources Information Center

    Lex, Barbara W.

    This paper selectively reviews current knowledge about the effects of alcohol, cocaine, and marijuana. Highlights of the review include findings that: (1) gender differences in alcohol and polysubstance users are reflected in epidemiological, biobehavioral, and neuroendocrine factors; (2) women and men exhibit different patterns of alcohol…

  5. Gene x Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

    SciTech Connect

    Alia-Klein, N.; Alia-Klein, N.; Parvaz, M.A.; Woicik, P.A.; Konova, A.B.; Maloney, T.; Shumay, E.; Wang, R.; Telang, F.; Biegon, A.; Wang, G.-J.; Fowler, J.S.; Tomasi, D.; Volkow, N.D.; Goldstein, R.Z.

    2011-03-07

    Long-term cocaine use has been associated with structural deficits in brain regions having dopamine-receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. The objective is to examine variations in gray matter volume (GMV) as a function of lifetime drug use and the genotype of the monoamine oxidase A gene, MAOA, in men with cocaine use disorders (CUD) and healthy male controls. Forty individuals with CUD and 42 controls who underwent magnetic resonance imaging to assess GMV and were genotyped for the MAOA polymorphism (categorized as high- and low-repeat alleles). The impact of cocaine addiction on GMV, tested by (1) comparing the CUD group with controls, (2) testing diagnosis x MAOA interactions, and (3) correlating GMV with lifetime cocaine, alcohol, and cigarette smoking, and testing their unique contribution to GMV beyond other factors. The results are: (1) Individuals with CUD had reductions in GMV in the orbitofrontal, dorsolateral prefrontal, and temporal cortex and the hippocampus compared with controls; (2) The orbitofrontal cortex reductions were uniquely driven by CUD with low- MAOA genotype and by lifetime cocaine use; and (3) The GMV in the dorsolateral prefrontal cortex and hippocampus was driven by lifetime alcohol use beyond the genotype and other pertinent variables. Long-term cocaine users with the low-repeat MAOA allele have enhanced sensitivity to gray matter loss, specifically in the orbitofrontal cortex, indicating that this genotype may exacerbate the deleterious effects of cocaine in the brain. In addition, long-term alcohol use is a major contributor to gray matter loss in the dorsolateral prefrontal cortex and hippocampus, and is likely to further impair executive function and learning in cocaine addiction.

  6. The Impact of Disulfiram Treatment on the Reinforcing Effects of Cocaine: A Randomized Clinical Trial

    PubMed Central

    Haile, Colin N.; De La Garza, Richard; Mahoney, James J.; Nielsen, David A.; Kosten, Thomas R.; Newton, Thomas F.

    2012-01-01

    Background Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users. Methods Seventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05–16) and in the other cocaine (20 mg) or money. Results Participants chose cocaine more than saline under both disulfiram and placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number of cocaine and saline infusion choices (p<0.05). We next examined the relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg bodyweight) was negatively correlated with number of choices for cocaine (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular measures (p's<0.05–0.01). Conclusions Disulfiram's impact on the reinforcing effects of cocaine depends on dose relative to body weight. Our results suggest that the use of weight-based medication doses would produce more reliable effects, consistent with weight-based dosing used in pediatrics and in preclinical research. Trial Registration Clinicaltrials.gov NCT00729300 PMID:23144826

  7. Cocaine/Crack: The Big Lie.

    ERIC Educational Resources Information Center

    National Inst. on Drug Abuse (DHHS/PHS), Rockville, MD.

    This pamphlet focuses on cocaine and crack use and the addictive nature of cocaine/crack. It contains a set of 21 questions about crack and cocaine, each accompanied by a clear and complete response. Interspersed throughout the booklet are photographs and quotes from former cocaine or crack users/addicts. Questions and answers focus on what…

  8. Language Outcomes at 12 Years for Children Exposed Prenatally to Cocaine

    ERIC Educational Resources Information Center

    Lewis, Barbara A.; Minnes, Sonia; Short, Elizabeth J.; Min, Meeyoung O.; Wu, Miaoping; Lang, Adelaide; Weishampel, Paul; Singer, Lynn T.

    2013-01-01

    Purpose: In this study, the authors aimed to examine the long-term effects of prenatal cocaine exposure (PCE) on the language development of 12-year-old children using a prospective design, controlling for confounding prenatal drug exposure and environmental factors. Method: Children who were exposed to cocaine in utero (PCE; "n" = 183)…

  9. Cocaine Intoxication and Thyroid Storm

    PubMed Central

    Lacy, Mary E.

    2014-01-01

    Introduction. Cocaine, a widely used sympathomimetic drug, causes thermoregulatory and cardiac manifestations that can mimic a life-threatening thyroid storm. Case. A man presented to the emergency department requesting only cocaine detoxification. He reported symptoms over the last few years including weight loss and diarrhea, which he attributed to ongoing cocaine use. On presentation he had an elevated temperature of 39.4°C and a heart rate up to 130 beats per minute. Examination revealed the presence of an enlarged, nontender goiter with bilateral continuous bruits. He was found to have thyrotoxicosis by labs and was treated for thyroid storm and cocaine intoxication concurrently. The patient was ultimately diagnosed with Graves’ disease and treated with iodine-131 therapy. Conclusion. Cocaine use should be considered a possible trigger for thyroid storm. Recognition of thyroid storm is critical because of the necessity for targeted therapy and the significant mortality associated with the condition if left untreated. PMID:26425625

  10. Covalent modification of proteins by cocaine

    NASA Astrophysics Data System (ADS)

    Deng, Shi-Xian; Bharat, Narine; Fischman, Marian C.; Landry, Donald W.

    2002-03-01

    Cocaine covalently modifies proteins through a reaction in which the methyl ester of cocaine acylates the -amino group of lysine residues. This reaction is highly specific in vitro, because no other amino acid reacts with cocaine, and only cocaine's methyl ester reacts with the lysine side chain. Covalently modified proteins were present in the plasma of rats and human subjects chronically exposed to cocaine. Modified endogenous proteins are immunogenic, and specific antibodies were elicited in mouse and detected in the plasma of human subjects. Covalent modification of proteins could explain cocaine's autoimmune effects and provide a new biochemical approach to cocaine's long-term actions.

  11. Regional Brain Morphometry and Impulsivity in Adolescents Following Prenatal Exposure to Cocaine and Tobacco

    PubMed Central

    Liu, Jie; Lester, Barry M.; Neyzi, Nurunisa; Sheinkopf, Stephen J.; Gracia, Luis; Kekatpure, Minal; Kosofsky, Barry E.

    2015-01-01

    Importance Animal studies have suggested that prenatal cocaine exposure (PCE) deleteriously influences the developing nervous system, in part attributable to its site of action in blocking the function of monoamine reuptake transporters, increasing synaptic levels of serotonin and dopamine. Objective To examine the brain morphologic features and associated impulsive behaviors in adolescents following prenatal exposure to cocaine and/or tobacco. Design Magnetic resonance imaging data and behavioral measures were collected from adolescents followed up longitudinally in the Maternal Lifestyle Study. Setting A hospital-based research center. Participants A total of 40 adolescent participants aged 13 to 15 years were recruited, 20 without PCE and 20 with PCE; a subset of each group additionally had tobacco exposure. Participants were selected and matched based on head circumference at birth, gestational age, maternal alcohol use, age, sex, race/ethnicity, IQ, family poverty, and socioeconomic status. Main Outcome Measures Subcortical volumetric measures of the thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens; cortical thickness measures of the dorsolateral prefrontal cortex and ventral medial prefrontal cortex; and impulsivity assessed by Conners' Continuous Performance Test and the Sensation Seeking Scale for Children. Results After controlling for covariates, cortical thickness of the right dorsolateral prefrontal cortex was significantly thinner in adolescents following PCE (P=.03), whereas the pallidum volume was smaller in adolescents following prenatal tobacco exposure (P=.03). Impulsivity was correlated with thalamic volume following either PCE (P=.05) or prenatal tobacco exposure (P=.04). Conclusions and Relevance Prenatal cocaine or tobacco exposure can differentially affect structural brain maturation during adolescence and underlie enhanced susceptibility to impulsivity. Additional studies with larger sample sizes are

  12. Design and control of glycerol-tert-butyl alcohol etherification process.

    PubMed

    Vlad, Elena; Bildea, Costin Sorin; Bozga, Grigore

    2012-01-01

    Design, economics, and plantwide control of a glycerol-tert-butyl alcohol (TBA) etherification plant are presented. The reaction takes place in liquid phase, in a plug flow reactor, using Amberlyst 15 as a catalyst. The products' separation is achieved by two distillation columns where high-purity ethers are obtained and a section involving extractive distillation with 1,4-butanediol as solvent, which separates TBA from the TBA/water azeotrope. Details of design performed in AspenPlus and an economic evaluation of the process are given. Three plantwide control structures are examined using a mass balance model of the plant. The preferred control structure fixes the fresh glycerol flow rate and the ratio glycerol + monoether : TBA at reactor-inlet. The stability and robustness in the operation are checked by rigorous dynamic simulation in AspenDynamics.

  13. Structure-affinity relationship of the cocaine-binding aptamer with quinine derivatives.

    PubMed

    Slavkovic, Sladjana; Altunisik, Merve; Reinstein, Oren; Johnson, Philip E

    2015-05-15

    In addition to binding its target molecule, cocaine, the cocaine-binding aptamer tightly binds the alkaloid quinine. In order to understand better how the cocaine-binding aptamer interacts with quinine we have used isothermal titration calorimetry-based binding experiments to study the interaction of the cocaine-binding aptamer to a series of structural analogs of quinine. As a basis for comparison we also investigated the binding of the cocaine-binding aptamer to a set of cocaine metabolites. The bicyclic aromatic ring on quinine is essential for tight affinity by the cocaine-binding aptamer with 6-methoxyquinoline alone being sufficient for tight binding while the aliphatic portion of quinine, quinuclidine, does not show detectable binding. Compounds with three fused aromatic rings are not bound by the aptamer. Having a methoxy group at the 6-position of the bicyclic ring is important for binding as substituting it with a hydrogen, an alcohol or an amino group all result in lower binding affinity. For all ligands that bind, association is driven by a negative enthalpy compensated by unfavorable binding entropy.

  14. Structure-affinity relationship of the cocaine-binding aptamer with quinine derivatives.

    PubMed

    Slavkovic, Sladjana; Altunisik, Merve; Reinstein, Oren; Johnson, Philip E

    2015-05-15

    In addition to binding its target molecule, cocaine, the cocaine-binding aptamer tightly binds the alkaloid quinine. In order to understand better how the cocaine-binding aptamer interacts with quinine we have used isothermal titration calorimetry-based binding experiments to study the interaction of the cocaine-binding aptamer to a series of structural analogs of quinine. As a basis for comparison we also investigated the binding of the cocaine-binding aptamer to a set of cocaine metabolites. The bicyclic aromatic ring on quinine is essential for tight affinity by the cocaine-binding aptamer with 6-methoxyquinoline alone being sufficient for tight binding while the aliphatic portion of quinine, quinuclidine, does not show detectable binding. Compounds with three fused aromatic rings are not bound by the aptamer. Having a methoxy group at the 6-position of the bicyclic ring is important for binding as substituting it with a hydrogen, an alcohol or an amino group all result in lower binding affinity. For all ligands that bind, association is driven by a negative enthalpy compensated by unfavorable binding entropy. PMID:25858454

  15. TOPIRAMATE’S EFFECTS ON COCAINE-INDUCED SUBJECTIVE MOOD, CRAVING, AND PREFERENCE FOR MONEY OVER DRUG TAKING

    PubMed Central

    Johnson, Bankole A.; Roache, John D.; Ait-Daoud, Nassima; Gunderson, Erik W.; Haughey, Heather M.; Wang, Xin-Qun; Liu, Lei

    2012-01-01

    Topiramate, presumably through antagonism of excitatory glutaminergic pathways and facilitation of inhibitory gamma-aminobutyric acid neurons in the cortico-mesolimbic system, might reduce cocaine’s abuse liability. We tested whether topiramate (100 mg twice daily) would reduce the euphoria, subjective mood, craving, and preference for cocaine over money induced by low and high doses (0.325 and 0.650 mg/kg i.v., respectively) of experimentally administered cocaine in 24 male and female, cocaine-dependent, non-treatment-seeking research volunteers in a university inpatient laboratory. We utilized a randomized, double-blind, placebo-controlled, within-subject, Latin-square crossover design in which 3 experimental challenge doses of low-dose cocaine, high-dose cocaine, and placebo were administered in counterbalanced order after 5 days of topiramate or matching placebo pretreatments separated by a 1-week washout period (2006–2009). After placebo pretreatments, cocaine produced dose-related increases in euphoria, stimulant effects, craving for more cocaine, and monetary value of cocaine in a behavioral preference test of cocaine vs. money choice. Topiramate pretreatment reduced the cocaine-related craving and monetary value of high-dose cocaine while increasing the monetary value, euphoria, and stimulant effects of low-dose cocaine. Validated and standardized human experimental methods evaluating the potential for topiramate to alter cocaine’s abuse liability suggest that topiramate may reduce the reinforcing effects and craving induced by higher cocaine doses. Low-dose cocaine might appear to have some enhancement of its stimulant properties in the presence of topiramate’s prominent sedative effects. PMID:23039088

  16. Brief coping skills treatment for cocaine abuse: 12-month substance use outcomes.

    PubMed

    Rohsenow, D J; Monti, P M; Martin, R A; Michalec, E; Abrams, D B

    2000-06-01

    Patients (N = 108) in a study of cocaine-specific coping skills training (CST), which was found to reduce cocaine use during a 3-month follow-up, were followed for an additional 9 months. CST involved coping skills training in the context of high-risk situations. Control treatment used meditation-relaxation. Both were added to comprehensive private substance abuse treatment. Patients in CST who relapsed had significantly fewer cocaine use days than did the control group during the first 6 months, then both conditions did equally well. Patients in CST also drank alcohol more frequently in the last 6 months than did contrast patients but did not differ in heavy drinking days. For cocaine use outcomes, no interaction of treatment was found with gender, education, route of administration, drug use severity, sociopathy, or depression. Implications include the need to investigate different lengths and combinations of treatment.

  17. Gene Cloning and Nucleotide Sequencing and Properties of a Cocaine Esterase from Rhodococcus sp. Strain MB1

    PubMed Central

    Bresler, Matthew M.; Rosser, Susan J.; Basran, Amrik; Bruce, Neil C.

    2000-01-01

    A strain of Rhodococcus designated MB1, which was capable of utilizing cocaine as a sole source of carbon and nitrogen for growth, was isolated from rhizosphere soil of the tropane alkaloid-producing plant Erythroxylum coca. A cocaine esterase was found to initiate degradation of cocaine, which was hydrolyzed to ecgonine methyl ester and benzoate; both of these esterolytic products were further metabolized by Rhodococcus sp. strain MB1. The structural gene encoding a cocaine esterase, designated cocE, was cloned from Rhodococcus sp. strain MB1 genomic libraries by screening recombinant strains of Rhodococcus erythropolis CW25 for growth on cocaine. The nucleotide sequence of cocE corresponded to an open reading frame of 1,724 bp that codes for a protein of 574 amino acids. The amino acid sequence of cocaine esterase has a region of similarity with the active serine consensus of X-prolyl dipeptidyl aminopeptidases, suggesting that the cocaine esterase is a serine esterase. The cocE coding sequence was subcloned into the pCFX1 expression plasmid and expressed in Escherichia coli. The recombinant cocaine esterase was purified to apparent homogeneity and was found to be monomeric, with an Mr of approximately 65,000. The apparent Km of the enzyme (mean ± standard deviation) for cocaine was measured as 1.33 ± 0.085 mM. These findings are of potential use in the development of a linked assay for the detection of illicit cocaine. PMID:10698749

  18. Cocaine Tolerance in Honey Bees

    PubMed Central

    Søvik, Eirik; Cornish, Jennifer L.; Barron, Andrew B.

    2013-01-01

    Increasingly invertebrates are being used to investigate the molecular and cellular effects of drugs of abuse to explore basic mechanisms of addiction. However, in mammals the principle factors contributing to addiction are long-term adaptive responses to repeated drug use. Here we examined whether adaptive responses to cocaine are also seen in invertebrates using the honey bee model system. Repeated topical treatment with a low dose of cocaine rendered bees resistant to the deleterious motor effects of a higher cocaine dose, indicating the development of physiological tolerance to cocaine in bees. Cocaine inhibits biogenic amine reuptake transporters, but neither acute nor repeated cocaine treatments caused measurable changes in levels of biogenic amines measured in whole bee brains. Our data show clear short and long-term behavioural responses of bees to cocaine administration, but caution that, despite the small size of the bee brain, measures of biogenic amines conducted at the whole-brain level may not reveal neurochemical effects of the drug. PMID:23741423

  19. Sigma receptors and cocaine abuse.

    PubMed

    Narayanan, Sanju; Mesangeau, Christophe; Poupaert, Jacques H; McCurdy, Christopher R

    2011-01-01

    Sigma receptors have been well documented as a protein target for cocaine and have been shown to be involved in the toxic and stimulant actions of cocaine. Strategies to reduce the access of cocaine to sigma receptors have included antisense oligonucleotides to the sigma-1 receptor protein as well as small molecule ligand with affinity for sigma receptor sites. These results have been encouraging as novel protein targets that can attenuate the actions of cocaine are desperately needed as there are currently no medications approved for treatment of cocaine toxicity or addiction. Many years of research in this area have yet to produce an effective treatment and much focus was on dopamine systems. A flurry of research has been carried out to elucidate the role of sigma receptors in the blockade of cocaine effects but this research has yet to yield a clinical agent. This review summarizes the work to date on the linkage of sigma receptors and the actions of cocaine and the progress that has been made with regard to small molecules. Although there is still a lack of an agent in clinical trials with a sigma receptor mechanism of action, work is progressing and the ligands are becoming more selective for sigma systems and the potential remains high. PMID:21050176

  20. Probing Cocaine-Antibody Interactions in Buffer and Human Serum

    PubMed Central

    Ramakrishnan, Muthu; Alves De Melo, Fernando; Kinsey, Berma M.; Ladbury, John E.; Kosten, Thomas R.; Orson, Frank M.

    2012-01-01

    metabolites provide valuable information for characterization of their interactions and thermodynamic properties. In addition MST measurements of antibody affinity in the presence of biological fluids will provide a better opportunity to make reliable decisions and facilitate the design of cocaine vaccines and immunization conditions. The methods should be more widely adopted in characterization of antibody complexes. PMID:22859949

  1. Autism and developmental abnormalities in children with perinatal cocaine exposure.

    PubMed Central

    Davis, E.; Fennoy, I.; Laraque, D.; Kanem, N.; Brown, G.; Mitchell, J.

    1992-01-01

    Cocaine in all forms is the number one illicit drug of choice among pregnant women. Records of 70 children with cocaine exposure in utero who were referred for developmental evaluation at a large inner-city hospital were reviewed in an effort to determine whether a specific pattern of abnormalities could be discerned. Patients received physical examinations, neurological screenings, and behavioral and developmental assessments based on the Gesell Developmental Inventory, and the Denver Developmental Screening Test. Documentation of specified drug use was obtained by history. Mean age (SEM) at referral was 19.2 (1.7) months. All mothers used cocaine in one of its forms, although polydrug use was common. Growth parameters were low (median = 15th percentile). Significant neurodevelopmental abnormalities were observed, including language delay in 94% of the children and an extremely high frequency of autism (11.4%). The high rate of autistic disorders not known to occur in children exposed to alcohol or opiates alone suggests specific cocaine effects. PMID:1380564

  2. Cocaine use among American adolescents and young adults.

    PubMed

    O'Malley, P M; Johnston, L D; Bachman, J G

    1985-01-01

    In this chapter, we have tried to provide some objective information about the levels of and recent trends in cocaine use among America's adolescents and young adults, as well as some of their attitudes and beliefs about the drug and their reasons for using it. We have also examined cross-time patterns of use, certain predictors of use, and some of the conditions of the social and physical environments which are associated with use. Overall, we have found levels of use to be relatively stable for the past several years after a period of rapid increase between 1976 and 1979. We also found a strong age effect, with cocaine use increasing in the first few years after high school. The levels of use, though stable recently, are disturbingly high, particularly among young adults in their early to mid twenties. Self reported use has followed patterns that parallel exposure to use and use by friend, as would be expected, assuming valid measures. Perceived availability also has moved in tandem with these other measures. The great majority of today's seniors believe regular use to be dangerous, and 77% disapprove of even experimenting with cocaine. Use is found most frequently in the western and northeastern regions of the country, in more urban areas, among males, and among those who are not college-bound. Neither socioeconomic status nor personal income are very strongly associated with use; but a history of truancy, going out frequently in the evenings, and having relatively low religious involvement are. Cocaine users tend to use other illicit drugs (particularly marijuana) and to be cigarette smokers and heavy drinkers much more frequently than nonusers. Thus, there is little evidence that cocaine involves a separate drug-using syndrome. In fact, it is not uncommon for cocaine users to use marijuana or alcohol concurrently. When taking cocaine, high school students most often snort it, though some (24% of recent users) smoke it while only 4% of the users inject it. It

  3. Transformation of cocaine during water chlorination.

    PubMed

    González-Mariño, Iria; Quintana, José Benito; Rodríguez, Isaac; Sánchez-Méndez, Noemí; Cela, Rafael

    2012-12-01

    The stability of cocaine and its two main human metabolites, benzoylecgonine and ecgonine methyl ester, in chlorine-containing waters has been investigated by direct injection of different reaction time aliquots in a liquid chromatograph (LC) coupled to a quadrupole-time-of-flight mass spectrometer (QTOF-MS). Factors potentially affecting cocaine degradation (the only compound showing a significant decrease in the preliminary study) were evaluated in detail by means of a Box-Behnken experimental design. Sample pH resulted to be the most important variable, increasing both the rate of chlorination-mediated reactions and the ester hydrolysis process. From these reactions, and due to the high mass accuracy measurements obtained with the QTOF system, four by-products could be positively identified: benzoylecgonine, norcocaine, norbenzoylecgonine and N-formylnorcocaine. Finally, their formation and cocaine degradation yields were assessed under chlorination experiments with two real surface water samples. In one of them, showing a low anthropogenic impact, benzoylecgonine and norcocaine were notably generated even after only 1 h of reaction, whereas at higher contact times also norbenzoylecgonine and N-formylnorcocaine could be determined with a lower yield. On the other hand, the second sample, with a higher organic matter content, consumed rapidly the chlorine, so that only benzoylecgonine was produced. These findings point out the convenience of monitoring the described transformation products, in addition to the precursor illicit drug, during drinking water production, taking into account that cocaine traces might be present in water catchments and particularly in areas with high population densities.

  4. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers.

    PubMed

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [(11)C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  5. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers

    PubMed Central

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [11C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  6. How to Design PET Experiments to Study Neurochemistry: Application to Alcoholism

    PubMed Central

    Morris, Evan D.; Lucas, Molly V.; Petrulli, J. Ryan; Cosgrove, Kelly P.

    2014-01-01

    Positron Emission Tomography (PET) (and the related Single Photon Emission Computed Tomography) is a powerful imaging tool with a molecular specificity and sensitivity that are unique among imaging modalities. PET excels in the study of neurochemistry in three ways: 1) It can detect and quantify neuroreceptor molecules; 2) it can detect and quantify changes in neurotransmitters; and 3) it can detect and quantify exogenous drugs delivered to the brain. To carry out any of these applications, the user must harness the power of kinetic modeling. Further, the quality of the information gained is only as good as the soundness of the experimental design. This article reviews the concepts behind the three main uses of PET, the rationale behind kinetic modeling of PET data, and some of the key considerations when planning a PET experiment. Finally, some examples of PET imaging related to the study of alcoholism are discussed and critiqued. PMID:24600335

  7. Effect of cocaine use on outcomes in traumatic brain injury

    PubMed Central

    Yeung, Jacky T; Williams, Jessica; Bowling, William M

    2013-01-01

    Context: Animal and molecular studies have shown that cocaine exerts a neuroprotective effect against cerebral ischemia. Aims: To determine if the presence of cocaine metabolites on admission following traumatic brain injury (TBI) is associated with better outcomes. Settings and Design: Level-1 trauma center, retrospective cohort. Materials and Methods: After obtaining Institutional Review Board (IRB) approval, the trauma registry was searched from 2006 to 2009 for all patients aged 15-55 years with blunt head trauma and non-head AIS <3. Exclusion criteria were pre-existing brain pathology and death within 30 min of admission. The primary outcome was in-hospital mortality; secondary outcomes were hospital length of stay (LOS), and Glasgow Outcome Score (GOS). Statistical Analysis: Logistic regression was used to determine the independent effect of cocaine on mortality. Hospital LOS was compared with multiple linear regression. Results: A total of 741 patients met criteria and had drug screens. The screened versus unscreened groups were similar. Cocaine positive patients were predominantly African-American (46% vs. 21%, P < 0.0001), older (40 years vs. 30 years, P < 0.0001), and had ethanol present more often (50.7% vs. 37.8%, P = 0.01). There were no differences in mortality (cocaine-positive 1.4% vs. cocaine-negative 2.7%, P = 0.6) on both univariate and multivariate analysis. Conclusions: Positive cocaine screening was not associated with mortality in TBI. An effect may not have been detected because of the low mortality rate. LOS is affected by many factors unrelated to the injury and may not be a good surrogate for recovery. Similarly, GOS may be too coarse a measure to identify a benefit. PMID:23960376

  8. Cocaine, Appetitive Memory and Neural Connectivity

    PubMed Central

    Ray, Suchismita

    2013-01-01

    This review examines existing cognitive experimental and brain imaging research related to cocaine addiction. In section 1, previous studies that have examined cognitive processes, such as implicit and explicit memory processes in cocaine users are reported. Next, in section 2, brain imaging studies are reported that have used chronic users of cocaine as study participants. In section 3, several conclusions are drawn. They are: (a) in cognitive experimental literature, no study has examined both implicit and explicit memory processes involving cocaine related visual information in the same cocaine user, (b) neural mechanisms underlying implicit and explicit memory processes for cocaine-related visual cues have not been directly investigated in cocaine users in the imaging literature, and (c) none of the previous imaging studies has examined connectivity between the memory system and craving system in the brain of chronic users of cocaine. Finally, future directions in the field of cocaine addiction are suggested. PMID:25009766

  9. Cocaine depresses GABAA current of hippocampal neurons.

    PubMed

    Ye, J H; Liu, P L; Wu, W H; McArdle, J J

    1997-10-01

    Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine-induced seizures, it is possible that other neurotransmitters such as gamma-aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current (IGABA) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed IGABA. The IC50 was 127 microM when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited IGABA non-competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of IGABA may contribute to cocaine-induced seizures.

  10. Neurobiological changes mediating the effects of chronic fluoxetine on cocaine use.

    PubMed

    Sawyer, Eileen K; Mun, Jiyoung; Nye, Jonathon A; Kimmel, Heather L; Voll, Ronald J; Stehouwer, Jeffrey S; Rice, Kenner C; Goodman, Mark M; Howell, Leonard L

    2012-07-01

    Acute SSRI (selective serotonin reuptake inhibitor) treatment has been shown to attenuate the abuse-related effects of cocaine; however, SSRIs have had limited success in clinical trials for cocaine abuse, possibly due to neurobiological changes that occur during chronic administration. In order to better understand the role of serotonin (5HT) in cocaine abuse and treatment, we examined the effects of chronic treatment with the SSRI fluoxetine at clinically relevant serum concentrations on cocaine-related neurobiology and behavior. Rhesus macaques self-administering cocaine underwent a 6-week dosing regimen with fluoxetine designed to approximate serum concentrations observed in humans. Self-administration and reinstatement were monitored throughout the treatment and washout period. In vivo microdiaylsis was used to assess changes in dopaminergic and serotonergic neurochemistry. Positron emission tomography was used to assess changes in the 5HT transporter and 2A receptor binding potential (BP). Functional output of the 5HT system was assessed using prolactin levels. Cocaine-primed reinstatement and cocaine-elicited dopamine overflow were significantly suppressed following chronic fluoxetine treatment. 5HT2A receptor BP was increased in the frontal cortex following treatment while prolactin release was blunted, suggesting desensitization of the 5HT2A receptor. These effects persisted after a 6-week washout period. Measures of pre-synaptic serotonergic function and cocaine self-administration were unaffected. These data demonstrate that acute and chronic fluoxetine treatments exert different effects on cocaine-related behavior. Furthermore, chronic fluoxetine treatment causes alterations in 5HT2A receptors in the frontal cortex that may selectively disrupt cocaine-primed reinstatement. Fluoxetine may not be useful for treatment of ongoing cocaine abuse but may be useful in relapse prevention. PMID:22434223

  11. Cocaine Use: 2002 and 2003. The NSDUH Report

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration, 2005

    2005-01-01

    Cocaine, including crack cocaine, was responsible for 12.8 percent of admissions to substance abuse treatment services in 2002.1 The National Survey on Drug Use and Health (NSDUH) asks persons aged 12 or older to report their use of illicit drugs, including cocaine. NSDUH defines cocaine use as use of cocaine in any form, including crack cocaine.…

  12. Treatment of cocaine craving with as-needed nalmefene, a partial κ opioid receptor agonist: first clinical experience.

    PubMed

    Grosshans, Martin; Mutschler, Jochen; Kiefer, Falk

    2015-07-01

    The treatment of cocaine dependence is difficult as no approved pharmacotherapy is available as yet. However, in preclinical and clinical trials, a variety of compounds were tested for suitability as inhibitors of craving for and relapse into the use of cocaine, among these antidepressants, antiepileptics, dopamine agonists, disulfiram, and naltrexone. Nalmefene, a structural derivative of naltrexone, shares with its parent compound approval (granted by the European Medical Agency in 2013) as a medication for the treatment of alcohol addiction in the European Union. It differs from naltrexone by a higher affinity for the δ opioid-receptors and a partial agonistic affinity to the κ opioid-receptors. It should be noted that patients addicted to cocaine show a considerable increase in κ receptors in the nucleus accumbens. This report describes the case of an abstinent cocaine-addicted patient regularly afflicted with cravings for cocaine. The patient took as-needed nalmefene for 5 months whenever she developed a craving for cocaine. For most of these interventions, the patient reported an abatement of craving and could avoid relapsing into cocaine consumption. This effect may be accounted for by nalmefene acting, other than naltrexone, as a partial agonist of the κ opioid-receptors. Therefore, nalmefene might be a promising new option in the pharmacological repertoire for the treatment of cocaine addiction.

  13. Alcoholism and Alcohol Abuse

    MedlinePlus

    ... This means that their drinking causes distress and harm. It includes alcoholism and alcohol abuse. Alcoholism, or ... brain, and other organs. Drinking during pregnancy can harm your baby. Alcohol also increases the risk of ...

  14. Cocaine-associated increase of atrial natriuretic peptides: an early predictor of cardiac complications in cocaine users?

    PubMed Central

    Casartelli, Alessandro; Dacome, Lisa; Tessari, Michela; Pascali, Jennifer; Bortolotti, Federica; Trevisan, Maria Teresa; Bosco, Oliviero; Cristofori, Patrizia; Tagliaro, Franco

    2014-01-01

    Objective Cocaine is known to produce life-threatening cardiovascular complications, and the investigation of the causes of death may be challenging in forensic medicine. The increasing knowledge of the cardiac function biomarkers and the increasing sensitivity of assays provide new tools in monitoring the cardiac life-threatening pathological conditions and in the sudden death investigation in chronic abusers. In this work, cardiac dysfunction was assessed in an animal model by measuring troponin I and natriuretic peptides as biomarkers, and considering other standard endpoints used in preclinical toxicology studies. Methods Lister Hooded rats were treated with cocaine in chronic self-administration studies. Troponin I (cTnI) and atrial natriuretic peptide (ANP) were evaluated at different time points and heart weight and histopathology were assessed at the end of the treatment period. Furthermore, cocaine and its main metabolites were measured in the rat fur to assess rats’ cocaine exposure. All the procedures and endpoints considered were designed to allow an easy and complete translation from the laboratory animals to human beings, and the same approach was also adopted with a group of 10 healthy cocaine abuse volunteers with no cardiac pathologies. Results Cardiac troponin I values were unaffected, and ANP showed an increasing trend with time in all cocaine-treated animals considered. Similarly, in the healthy volunteers, no changes were observed in troponin serum levels, whereas the N-terminal brain natriuretic pro-peptide (NT proBNP) showed variations comparable with the changes observed in rats. Conclusions In conclusion, natriuretic peptides could represent an early indicator of heart dysfunction liability in chronic cocaine abusers. PMID:27326180

  15. Nanomaterial-based cocaine aptasensors.

    PubMed

    Mokhtarzadeh, Ahad; Dolatabadi, Jafar Ezzati Nazhad; Abnous, Khalil; de la Guardia, Miguel; Ramezani, Mohammad

    2015-06-15

    Up to now, many different methods have been developed for detection of cocaine, but most of these methods are usually time-consuming, tedious and require special or expensive equipment. Therefore, the development of simple, sensitive and rapid detection methods is necessary. In the last decade, aptamers have been used as a new biosensor platform for detection of cocaine in different samples. Aptamers are artificial single-stranded DNA or RNA oligonucleotides capable of binding to specific molecular targets with high affinity and if integrated to nanomaterials, it may lead in precise methods for cocaine detection in the common laboratories. In this review, recent advances and applications of aptamer-based biosensors and nanobiosensors, have been updated, paying attention to the use of fluorescence, colorimetric and electrochemical techniques for the detection and quantitative determination of cocaine.

  16. The Obsessive Compulsive Cocaine Scale: Assessment of Factor Structure, Reliability, and Validity

    PubMed Central

    Jardin, Bianca F.; LaRowe, Steven D.; Hall, Brian J.; Malcolm, Robert J.

    2011-01-01

    The present study assessed the factor structure, reliability, test retest, convergent validity, and predictive validity of the Obsessive Compulsive Cocaine Scale (OCCS), a newly developed questionnaire adapted from the Obsessive Compulsive Drinking Scale (OCDS). The questionnaire was administered to 189 cocaine-dependent individuals participating in two medication treatment trials for cocaine dependence. Confirmatory factor analysis of this measure revealed that it primarily assesses two factors, obsessions and compulsions. In addition, the data provided strong support for the internal consistency, test-retest reliability, predictive validity, and convergent validity of this two-factor measure. Overall, the data provide support for the psychometric strength of a modified version of the OCDS specifically designed to assess obsessive and compulsive cocaine use among those with cocaine dependence. PMID:21862227

  17. The Obsessive Compulsive Cocaine Scale: assessment of factor structure, reliability, and validity.

    PubMed

    Jardin, Bianca F; Larowe, Steven D; Hall, Brian J; Malcolm, Robert J

    2011-12-01

    The present study assessed the factor structure, reliability, test retest, convergent validity, and predictive validity of the Obsessive Compulsive Cocaine Scale (OCCS), a newly developed questionnaire adapted from the Obsessive Compulsive Drinking Scale (OCDS). The questionnaire was administered to 189 cocaine-dependent individuals participating in two medication treatment trials for cocaine dependence. Confirmatory factor analysis of this measure revealed that it primarily assesses two factors, obsessions and compulsions. In addition, the data provided strong support for the internal consistency, test-retest reliability, predictive validity, and convergent validity of this two-factor measure. Overall, the data provide support for the psychometric strength of a modified version of the OCDS specifically designed to assess obsessive and compulsive cocaine use among those with cocaine dependence.

  18. [A brief review on cocaine].

    PubMed

    Renggli, R

    1985-03-30

    Alongside the much more familiar heroin, cocaine is assuming increasing importance. This one-time cultivated plant of the Indios is thriving again and posing new problems in the therapy of drug abuse. To assist the general practitioner, who is increasingly confronted with drug problems, a brief report is presented on the origins, history, use and effects of cocaine. Finally, some pointers for therapy are given.

  19. Prenatal Cocaine Exposure: The South Looks for Answers. A SACUS Special Report.

    ERIC Educational Resources Information Center

    Shores, Elizabeth F.

    This special report provides answers to six fundamental questions on prenatal cocaine exposure: (1) What problems do drug-exposed newborns have? (2) How many of these children are there? (3) How do we get pregnant women to avoid drugs and alcohol? (4) What should be done to help the families of substance abusers? (5) How do drug-exposed children…

  20. Response contingency directs long-term cocaine-induced neuroplasticity in prefrontal and striatal dopamine terminals.

    PubMed

    Wiskerke, Joost; Schoffelmeer, Anton N M; De Vries, Taco J

    2016-10-01

    Exposure to addictive substances such as cocaine is well-known to alter brain organisation. Cocaine-induced neuroadaptations depend on several factors, including drug administration paradigm. To date, studies addressing the consequences of cocaine exposure on dopamine transmission have either not been designed to investigate the role of response contingency or focused only on short-term neuroplasticity. We demonstrate a key role of response contingency in directing long-term cocaine-induced neuroplasticity throughout projection areas of the mesocorticolimbic dopamine system. We found enhanced electrically-evoked [(3)H]dopamine release from superfused brain slices of nucleus accumbens shell and core, dorsal striatum and medial prefrontal cortex three weeks after cessation of cocaine self-administration. In yoked cocaine rats receiving the same amount of cocaine passively, sensitised dopamine terminal reactivity was only observed in the nucleus accumbens core. Control sucrose self-administration experiments demonstrated that the observed neuroadaptations were not the result of instrumental learning per se. Thus, long-term withdrawal from cocaine self-administration is associated with widespread sensitisation of dopamine terminals throughout frontostriatal circuitries. PMID:27593624

  1. Systems-level view of cocaine addiction: the interconnection of the immune and nervous systems.

    PubMed

    Marasco, Christina C; Goodwin, Cody R; Winder, Danny G; Schramm-Sapyta, Nicole L; McLean, John A; Wikswo, John P

    2014-11-01

    The human body is a complex assembly of physiological systems designed to manage the multidirectional transport of both information and nutrients. An intricate interplay between the nervous, circulatory, and secretory systems is therefore necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and eliminate metabolic waste products and toxins. These systems also provide vulnerable routes for modification by substances of abuse. Addictive substances are, by definition, neurologically active, but as they and their metabolites are spread throughout the body via the nervous, circulatory, respiratory and digestive systems, there is abundant opportunity for interaction with numerous cell and tissue types. Cocaine is one such substance that exerts a broad physiological effect. While a great deal of the research concerning addiction has addressed the neurological effects of cocaine use, only a few studies have been aimed at delineating the role that cocaine plays in various body systems. In this paper, we probe the current research regarding cocaine and the immune system, and map a systems-level view to outline a broader perspective of the biological response to cocaine. Specifically, our overview of the neurological and immunomodulatory effects of the drug will allow a broader perspective of the biological response to cocaine. The focus of this review is on the connection between the nervous and immune systems and the role this connection plays in the long-term complications of cocaine use. By describing the multiplicity of these connections, we hope to inspire detailed investigations into the immunological interplay in cocaine addiction. PMID:24903164

  2. Systems-level view of cocaine addiction: the interconnection of the immune and nervous systems.

    PubMed

    Marasco, Christina C; Goodwin, Cody R; Winder, Danny G; Schramm-Sapyta, Nicole L; McLean, John A; Wikswo, John P

    2014-11-01

    The human body is a complex assembly of physiological systems designed to manage the multidirectional transport of both information and nutrients. An intricate interplay between the nervous, circulatory, and secretory systems is therefore necessary to sustain life, allow delivery of nutrients and therapeutic drugs, and eliminate metabolic waste products and toxins. These systems also provide vulnerable routes for modification by substances of abuse. Addictive substances are, by definition, neurologically active, but as they and their metabolites are spread throughout the body via the nervous, circulatory, respiratory and digestive systems, there is abundant opportunity for interaction with numerous cell and tissue types. Cocaine is one such substance that exerts a broad physiological effect. While a great deal of the research concerning addiction has addressed the neurological effects of cocaine use, only a few studies have been aimed at delineating the role that cocaine plays in various body systems. In this paper, we probe the current research regarding cocaine and the immune system, and map a systems-level view to outline a broader perspective of the biological response to cocaine. Specifically, our overview of the neurological and immunomodulatory effects of the drug will allow a broader perspective of the biological response to cocaine. The focus of this review is on the connection between the nervous and immune systems and the role this connection plays in the long-term complications of cocaine use. By describing the multiplicity of these connections, we hope to inspire detailed investigations into the immunological interplay in cocaine addiction.

  3. Reducing effect of saikosaponin A, an active ingredient of Bupleurum falcatum, on alcohol self-administration in rats: Possible involvement of the GABAB receptor.

    PubMed

    Maccioni, Paola; Lorrai, Irene; Carai, Mauro A M; Riva, Antonella; Morazzoni, Paolo; Mugnaini, Claudia; Corelli, Federico; Gessa, Gian Luigi; Colombo, Giancarlo

    2016-05-16

    Recent studies demonstrated that treatment with saikosaponin A (SSA) - an active ingredient of the medicinal herb, Bupleurum falcatum L. - selectively suppressed, likely via a GABAB receptor-mediated mechanism, intravenous self-administration of morphine and cocaine in rats [Yoon et al., 2012; 2013]. The present study was designed to investigate whether the capacity of SSA to suppress morphine and cocaine self-administration extends to oral alcohol self-administration. To this end, selectively bred Sardinian alcohol-preferring (sP) rats were trained to lever-respond on a Fixed Ratio (FR) 4 (FR4) schedule of reinforcement for alcohol (15%, v/v) in daily 30-min sessions. Once responding had stabilized, rats were tested under the FR4 (measure of alcohol reinforcing properties) and Progressive Ratio (PR; measure of alcohol motivational properties) schedules of reinforcement. The possible involvement of the GABAB receptor system was investigated testing the effect of (a) pretreatment with the GABAB receptor antagonist, SCH50911, and (b) combined treatment with the positive allosteric modulator of the GABAB receptor, GS39783. Treatment with SSA (0, 0.25, 0.5, and 1mg/kg, i.p.) markedly reduced lever-responding for alcohol, amount of self-administered alcohol, and breakpoint for alcohol (defined as the lowest response requirement not achieved in the PR experiment). Pretreatment with 2mg/kg SCH50911 (i.p.) resulted in a partial blockade of the reducing effect of 0.5mg/kg SSA on lever-responding for alcohol and amount of self-administered alcohol. Combination of per se ineffective doses of GS39783 (5mg/kg, i.g.) and SSA (0.1mg/kg, i.p.) reduced lever-responding for alcohol and amount of self-administered alcohol. These results (a) extend to alcohol self-administration the capacity of SSA to suppress morphine and cocaine self-administration in rats and (b) suggest that the GABAB receptor system is likely part of the neural substrate underlying the reducing effect of SSA on

  4. An Evolution of Virtual Reality Training Designs for Children With Autism and Fetal Alcohol Spectrum Disorders

    PubMed Central

    Strickland, Dorothy C.; McAllister, David; Coles, Claire D.; Osborne, Susan

    2009-01-01

    This article describes an evolution of training programs to use first-person interaction in virtual reality (VR) situations to teach safety skills to children with autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD). Multiple VR programs for children aged 2 to 9 were built and tested between 1992 and 2007. Based on these results, a learning design evolved that uses practice in virtual space with guidance and correction by an animated character, strategic limitations on allowed actions to force correct patterning, and customization of worlds and responses to simplify user controls. This article describes program evolution by comparing design details and results as variations in behavioral responses between disorders, differences in skill set complexity between different safety skills being taught, and improved technology required changes in the virtual training methodology. A series of research projects are summarized in which the VR programs proved effective for teaching children with ASD and FASD new skills in the virtual space and, where measured, most children generalized the actions to the real world. PMID:20072702

  5. Crack/cocaine users show more family problems than other substance users

    PubMed Central

    Moura, Helena Ferreira; Benzano, Daniela; Pechansky, Flavio; Kessler, Felix Henrique Paim

    2014-01-01

    OBJECTIVES: To evaluate family problems among crack/cocaine users compared with alcohol and other substance users. METHODS: A cross-sectional multi-center study selected 741 current adult substance users from outpatient and inpatient Brazilian specialized clinics. Subjects were evaluated with the sixth version of the Addiction Severity Index, and 293 crack users were compared with 126 cocaine snorters and 322 alcohol and other drug users. RESULTS: Cocaine users showed more family problems when compared with other drug users, with no significant difference between routes of administration. These problems included arguing (crack 66.5%, powder cocaine 63.3%, other drugs 50.3%, p = 0.004), having trouble getting along with partners (61.5%×64.6%×48.7%, p = 0.013), and the need for additional childcare services in order to attend treatment (13.3%×10.3%×5.1%, p = 0.002). Additionally, the majority of crack/cocaine users had spent time with relatives in the last month (84.6%×86.5%×76.6%, p = 0.011). CONCLUSIONS: Brazilian treatment programs should enhance family treatment strategies, and childcare services need to be included. PMID:25029583

  6. Design, Synthesis and Biological Evaluation of Aminoalkylindole Derivatives as Cannabinoid Receptor Ligands with Potential for Treatment of Alcohol Abuse

    PubMed Central

    Vasiljevik, Tamara; Franks, Lirit N.; Ford, Benjamin M.; Douglas, Justin T.; Prather, Paul L.; Fantegrossi, William E.; Prisinzano, Thomas E.

    2013-01-01

    Attenuation of increased endocannabinoid signaling with a CB1R neutral antagonist might offer a new therapeutic direction for treatment of alcohol abuse. We have recently reported that a mono-hydroxylated metabolite of the synthetic aminoalkylindole cannabinoid JHW-073 (3) exhibits neutral antagonist activity at CB1Rs and thus may serve as a promising lead for the development of novel alcohol abuse therapies. In the current study, we show that systematic modification of an aminoalkylindole scaffold identified two new compounds with dual CB1R antagonist/CB2R agonist activity. Similar to the CB1R antagonist/inverse agonist rimonabant, analogues 27 and 30 decrease oral alcohol self-administration, without affecting total fluid intake and block the development of alcohol-conditioned place preference. Collectively, these initial findings suggest that design and systematic modification of aminoalkylindoles such as 3 may lead to development of novel cannabinoid ligands with dual CB1R antagonist/CB2R agonist activity with potential for use as treatments of alcohol abuse. PMID:23631463

  7. Cocaine and "pharmacological kindling" in the rat.

    PubMed

    Stripling, J S

    1983-11-01

    The concept of "pharmacological kindling" has been used to explain the behavioral sensitization to cocaine produced by repeated administration of subconvulsive doses. This idea was tested by the repeated administration of cocaine to rats followed by electrical kindling of the olfactory bulb (a site at which cocaine has prominent electrophysiologic effects). No significant effect of cocaine on kindling was found. The relationship of this finding to studies using other drugs is discussed.

  8. Pyrolysis and volatilization of cocaine

    SciTech Connect

    Martin, B.R.; Lue, L.P.; Boni, J.P. )

    1989-05-01

    The increasing popularity of inhaling cocaine vapor prompted the present study, to determine cocaine's fate during this process. The free base of (3H)cocaine (1 microCi/50 mg) was added to a glass pipe, which was then heated in a furnace to simulate freebasing. Negative pressure was used to draw the vapor through a series of glass wool, ethanol, acidic, and basic traps. Air flow rate and temperature were found to have profound effects on the volatilization and pyrolysis of cocaine. At a temperature of 260 degrees C and a flow rate of 400 mL/min, 37% of the radioactivity remained in the pipe, 39% was found in the glass wool trap, and less than 1% in the remainder of the volatilization apparatus after a 10-min volatilization. Reducing the air flow rate to 100 mL/min reduced the amount of radioactivity collected in the glass wool trap to less than 10% of the starting material and increased the amount that remained in the pipe to 58%. GC/MS analysis of the contents of the glass wool trap after volatilization at 260 degrees C and a flow rate of 400 mL/min revealed that 60% of the cocaine remained intact, while approximately 6 and 2% of the starting material was recovered as benzoic acid and methylecgonidine, respectively. As the temperature was increased to 650 degrees C, benzoic acid and methylecgonidine accounted for 83 and 89% of the starting material, respectively, whereas only 2% of the cocaine remained intact. Quantitation of cocaine in the vapor during the course of volatilization revealed high concentrations during the first two min and low concentrations for the remaining time.

  9. Learning Innovative Maternal Instinct: Activity Designing Semantic Factors of Alcohol Modification in Rural Communities of Thailand

    ERIC Educational Resources Information Center

    Yodmongkol, Pitipong; Jaimung, Thunyaporn; Chakpitak, Nopasit; Sureephong, Pradorn

    2014-01-01

    At present, Thailand is confronting a serious problem of alcohol drinking behavior which needs to be solved urgently. This research aimed to identify the semantic factors on alcohol drinking behavior and to use maternal instinct driving for housewives as village health volunteers in rural communities, Thailand. Two methods were implemented as the…

  10. Young Adult Male Satisfaction with Drug & Alcohol Rehabilitation Facilities: Interior Design Implications.

    ERIC Educational Resources Information Center

    Potthoff, Joy K.

    1991-01-01

    Examined young adult male patient (n=18) satisfaction with interior environments of three different in-patient drug and alcohol rehabilitation facilities: renovated Elk's Club; hospital wing; and facility built for drug and alcohol treatment. Findings indicated satisfaction declined over four-week treatment period; familiar objects were missed;…

  11. Self-administration of cocaine-pentobarbital mixtures by rhesus monkeys.

    PubMed

    Woolverton, W L; Wang, Zhixia

    2009-03-01

    A number of experiments have evaluated self-administration of the combination of a stimulant and an opioid. Less is known about the combination of a stimulant and a CNS depressant. The present experiment was designed to examine self-administration of the mixture of cocaine and pentobarbital (PB). Rhesus monkeys (n=4) prepared with i.v. catheters were allowed to self-administer cocaine or saline under a progressive-ratio schedule. When responding was stable, doses of cocaine and PB, alone or in combination, were made available in test sessions. Cocaine functioned as a positive reinforcer in a dose-related manner in all monkeys. PB functioned as a relatively weaker reinforcer in one of four monkeys. Self-administration of intermediate doses of cocaine (0.025-0.1mg/kg per injection) was decreased when mixed with PB (0.05-0.2mg/kg per injection); full maximum responding was re-established when cocaine dose was increased. The magnitude of the shift to the right in the cocaine dose-response function was directly related to PB dose. When PB was given as an i.v. pretreatment there was no effect on cocaine self-administration up to a sedative dose of PB (5.6 mg/kg), suggesting that responding was not non-specifically suppressed by PB. Thus, simultaneous self-administration of PB diminished the potency but not the strength of cocaine as a reinforcer, potentially encouraging self-administration of larger doses of cocaine. PMID:19054630

  12. Discriminative and reinforcing stimulus effects of nicotine, cocaine, and cocaine + nicotine combinations in rhesus monkeys.

    PubMed

    Mello, Nancy K; Newman, Jennifer L

    2011-06-01

    Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was twofold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine's discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications. PMID:21480727

  13. Ibudilast attenuates expression of behavioral sensitization to cocaine in male and female rats.

    PubMed

    Poland, Ryan S; Hahn, Yun K; Knapp, Pamela E; Beardsley, Patrick M; Bowers, M Scott

    2016-10-01

    There are no FDA-approved pharmacotherapies for cocaine use disorder, indicating a need to identify novel reagents with therapeutic potential. Ibudilast is an anti-inflammatory glial attenuator and non-selective phosphodiesterase inhibitor currently undergoing clinical evaluations for methamphetamine, opiate, and alcohol abuse disorders. We previously showed that twice daily (b.i.d.) ibudilast reduces the development of methamphetamine sensitization in male mice. However, nothing is known about the ability of ibudilast to modulate the expression of sensitization that occurs after drug re-exposure during abstinence, effects on cocaine-mediated behaviors, or potentially sexually dimorphic effects. Male and female rats were administered cocaine for 7 days and expression of sensitization was assessed by cocaine challenge after 21 days abstinence. On test days, 15 mg/kg i. p. cocaine was evaluated, whereas 30 mg/kg was administered on intervening days. Lower test doses avoid competition of non-motor behaviors with locomotion. In all measures where sensitization was expressed, ibudilast (7.5 and 10 mg/kg, i. p., b. i.d. for 3 days and once on test day) reversed this behavior to levels seen after acute exposure, but not below. There were some intriguing sexually dimorphic effects that were not a function of estrous cycle. Specifically, distance travelled in the center of the test arena and rearing only sensitized in male rats, and ibudilast reversed these behaviors to levels seen after acute cocaine exposure. In females, center distance travelled was reduced below acute cocaine levels by 7.5 mg/kg ibudilast. Increased distance travelled in the center versus periphery is thought to model anxiolytic-like behavior due to increased predation risk. Taken together, these data suggest that the clinical evaluation of ibudilast could be extended to cocaine use disorder. PMID:27343385

  14. α2δ-1 Signaling in Nucleus Accumbens Is Necessary for Cocaine-Induced Relapse

    PubMed Central

    Brown, Robyn M.; Quintero, Gabriel C.; Kupchik, Yonatan M.; Thomas, Charles A.; Reissner, Kathryn J.; Kalivas, Peter W.

    2014-01-01

    Relapse to cocaine seeking is associated with potentiated excitatory synapses in nucleus accumbens. α2δ-1 is an auxiliary subunit of voltage-gated calcium channels that affects calcium-channel trafficking and kinetics, initiates extracellular signaling cascades, and promotes excitatory synaptogenesis. Previous data demonstrate that repeated exposure to alcohol, nicotine, methamphetamine, and morphine upregulates α2δ-1 in reward-related brain regions, but it was unclear whether this alteration generalized to cocaine. Here, we show that α2δ-1 protein was increased in nucleus accumbens after cocaine self-administration and extinction compared with saline controls. Furthermore, the endogenous ligand thrombospondin-1, responsible for the synaptogenic properties of the α2δ-1 receptor, was likewise elevated. Using whole-cell patch-clamp recordings of EPSCs in nucleus accumbens, we demonstrated that gabapentin, a specific α2δ-1 antagonist, preferentially reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation in slices from cocaine-experienced rats compared with controls. In vivo, gabapentin microinjected in the nucleus accumbens core attenuated cocaine-primed but not cue-induced reinstatement. Importantly, gabapentin's effects on drug seeking were not due to a general depression of spontaneous or cocaine-induced locomotor activity. Moreover, gabapentin had no effect on reinstatement of sucrose seeking. These data indicate that α2δ-1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. These results also inform ongoing discussion in the literature regarding efficacy of gabapentin as a candidate addiction therapy. PMID:24948814

  15. Growth, Development, and Behavior in Early Childhood Following Prenatal Cocaine Exposure

    PubMed Central

    Frank, Deborah A.; Augustyn, Marilyn; Knight, Wanda Grant; Pell, Tripler; Zuckerman, Barry

    2008-01-01

    , scope, or kind from the sequelae of multiple other risk factors. Many findings once thought to be specific effects of in utero cocaine exposure are correlated with other factors, including prenatal exposure to tobacco, marijuana, or alcohol, and the quality of the child’s environment. Further replication is required of preliminary neurologic findings. PMID:11268270

  16. Unrecognized "crack" cocaine abuse in pregnancy.

    PubMed

    Campbell, D; Parr, M J; Shutt, L E

    1996-10-01

    We report a case of "crack" cocaine abuse in a pregnant patient associated with haematuria, proteinuria, haemolytic anaemia, renal impairment, thrombocytopenia and pulmonary oedema. The case illustrates the problems for clinicians where unrecognized cocaine abuse interferes with the diagnosis and management of a complicated pregnancy. In addition, we discuss the principles for the safe conduct of anaesthesia in the pregnant cocaine abuser.

  17. Prenatal Cocaine Exposure and Infant Cortisol Reactivity

    ERIC Educational Resources Information Center

    Eiden, Rina D.; Veira, Yvette; Granger, Douglas A.

    2009-01-01

    This study examined the effects of prenatal cocaine exposure on infant hypothalamic-pituitary-adrenal axis activity and reactivity at 7 months of infant age. Participants were 168 caregiver-infant dyads (87 cocaine exposed, 81 not cocaine exposed; 47% boys). Maternal behavior, caregiving instability, and infant growth and behavior were assessed,…

  18. Cerebral vasculitis associated with cocaine abuse

    SciTech Connect

    Kaye, B.R.; Fainstat, M.

    1987-10-16

    A case of cerebral vasculitis in a previously healthy 22-year-old man with a history of cocaine abuse is described. Cerebral angiograms showed evidence of vasculitis. A search for possible causes other than cocaine produced no results. The authors include cocaine with methamphetamines, heroin, and ephedrine as illicit drugs that can cause cerebral vasculitis.

  19. Unrecognized "crack" cocaine abuse in pregnancy.

    PubMed

    Campbell, D; Parr, M J; Shutt, L E

    1996-10-01

    We report a case of "crack" cocaine abuse in a pregnant patient associated with haematuria, proteinuria, haemolytic anaemia, renal impairment, thrombocytopenia and pulmonary oedema. The case illustrates the problems for clinicians where unrecognized cocaine abuse interferes with the diagnosis and management of a complicated pregnancy. In addition, we discuss the principles for the safe conduct of anaesthesia in the pregnant cocaine abuser. PMID:8942348

  20. Recent developments in the abuse of cocaine.

    PubMed

    Cohen, S

    1984-01-01

    Cocaine is a powerful euphoriant and it relieves, though only transiently, depression, dread and dysphoria. New patterns of cocaine abuse, such as the inhalation of vaporized cocaine base, the intravenous injection of cocaine hydrochloride and the smoking of coca paste, produce a brief elation that quickly gives way either to a return to the baseline mood or to displeasure, resulting in a strong desire to return to the momentary ecstatic experience, a cycle that leads to compulsive use. The enormous profits made from illicit traffic in cocaine lead to corruption, violence and political destabilization. The individual costs of cocaine abuse include loss of personal fortunes, jobs and families. The safety of cocaine use is a myth. There are a number of ways in which cocaine can be lethal. The high doses of cocaine abused today induce physical dependence, but this is less a contributory factor than the intense psychological craving to perpetuate cocaine use. There is no specific way to treat dysfunctional cocaine use; instead the treatment plan must deal with the individual's specific situation. Except for a reduction of cocaine supply at the source, preventive measures are only feasible in the context of abstinence from all abusable drugs.

  1. Effects of extended cocaine access and cocaine withdrawal on choice between cocaine and food in rhesus monkeys.

    PubMed

    Banks, Matthew L; Negus, S Stevens

    2010-01-01

    Chronic drug use may lead to sufficient drug intake to produce dependence and the emergence of abstinence signs during withdrawal. Although withdrawal can increase the reinforcing effects of some drugs (eg opioids), the impact of withdrawal on the reinforcing effects of stimulants like cocaine is less clear. This study used a novel cocaine vs food choice procedure to examine the relative reinforcing strength of cocaine before, during, and after exposure to graded levels of extended cocaine access. Responding in four rhesus monkeys was maintained by cocaine (0-0.1 mg/kg/injection) and food delivery under a concurrent-choice schedule during daily 2-h sessions. Under baseline conditions, cocaine maintained a dose-dependent increase in cocaine choice. Subsequently, subjects were exposed to and withdrawn from periods of extended cocaine access, which was accomplished by implementing daily 21-h supplemental sessions of cocaine self-administration in addition to daily choice sessions. During supplemental sessions, cocaine (0.1 mg/kg/injection) was available under a fixed-ratio 10/time-out X schedule, and the duration of the time-out was varied from 30 to 7.5 min. Cocaine intake increased 10-fold to >11 mg/kg/day during exposure to supplemental sessions with the shortest post-injection time-out. However, parameters of cocaine choice were not significantly affected either during or after extended cocaine access. These results do not support the hypothesis that cocaine withdrawal increases the reinforcing strength of cocaine. This differs from results with the opioid agonist heroin and suggests that withdrawal may have different functions in the maintenance of opioid and stimulant abuse. PMID:19776729

  2. Description and quantification of cocaine withdrawal signs in Planaria.

    PubMed

    Raffa, Robert B; Desai, Prarthna

    2005-01-25

    Previous work provided indirect evidence that planarians undergo abstinence-induced withdrawal from cocaine. The present study's purpose was to determine if planarians display withdrawal signs and, if so, to quantify the behaviors. Planarians were soaked in cocaine then transferred to either the same cocaine concentration or cocaine-free water. Compared to the cocaine/cocaine group, the cocaine/water group displayed a significant number of atypical behaviors, providing direct evidence of a 'withdrawal phenomenon' in planarians.

  3. Post-treatment drinking among HIV patients: Relationship to pre-treatment marijuana and cocaine use

    PubMed Central

    Elliott, Jennifer C.; Aharonovich, Efrat; Hasin, Deborah S.

    2016-01-01

    BACKGROUND For individuals with HIV, heavy drinking can pose serious threats to health. Some interventions are effective at reducing drinking in this population, but many HIV-infected heavy drinkers also use marijuana or cocaine. Although these drugs have predicted poor alcohol outcomes in other treatment studies, whether this occurs among HIV patients who drink heavily is unknown. METHODS Participants were binge-drinking HIV primary care patients (N=254) enrolled in a randomized trial of three brief drinking interventions over 60 days that varied in intensity. We investigated the relationship of baseline past-year drug use (marijuana-only, cocaine-only, both, neither) to end-of-treatment drinking quantity and frequency. We also evaluated whether the relationship between intervention type and end-of-treatment drinking varied by baseline drug use. Final models incorporated control for patients’ demographic and HIV characteristics. RESULTS In final models, drinking frequency at the end of treatment did not vary by baseline drug use, but drinking quantity did (X2 [3] = 13.87, p<0.01), with individuals using cocaine-only drinking significantly more per occasion (B=0.32, p<0.01). Baseline drug use also interacted with intervention condition in predicting end-of-treatment drinking quantity (X2 [6] = 13.98, p<0.05), but not frequency, with the largest discrepancies in end-of-treatment drinks per drinking day by intervention intensity among cocaine-only patients. CONCLUSIONS In general, HIV patients using cocaine evidenced the highest levels of drinking after alcohol intervention. However, these individuals also evidenced the most pronounced differences in end-of-treatment drinking by intervention intensity. These results suggest the importance of more intensive intervention for individuals using alcohol and cocaine. PMID:25920801

  4. Design and manufacture of a polyvinyl alcohol (PVA) cryogel tri-leaflet heart valve prosthesis.

    PubMed

    Jiang, Hongjun; Campbell, Gord; Boughner, Derek; Wan, Wan-Kei; Quantz, Mackenzie

    2004-05-01

    Although current artificial heart valves are life sustaining medical devices, improvements are still necessary to address deficiencies. Bioprosthetic valves have a compromised fatigue life, while mechanical valves have better durability but are prone to thromboembolic complications. A novel, one-piece, tricuspid valve, consisting of leaflets, stent and sewing ring, made entirely from the hydrogel, polyvinyl alcohol cryogel (PVA-C), has been developed and demonstrated. This valve has three thin leaflets attached to a cylindrical stent. In order to approximate the complex shape of the surface of the natural heart valve leaflets, two different geometries have been proposed: revolution about an axis of a hyperboloid shape and revolution about an axis of an arc subtending (joining) two straight lines. The parameters of both geometries were examined based on a compromise between avoiding sharp curvature of leaflets and minimization of the central opening of the valve when closed. The revolution of an arc subtending two straight lines was selected as the preferred geometry since it has the benefit of a smaller central opening when the value of the maximum curvature for the leaflets is the same for each valve geometry. A cavity mold has been designed and constructed to form the PVA-C heart valve. The three leaflets were formed and integrated into the stent and sewing ring in a single process. Prototype heart valves were manufactured in the mold from a solution of PVA and water, by controlled freezing and thawing cycles. PMID:15121052

  5. Preventing Abuse of Drugs, Alcohol, and Tobacco by Adolescents.

    ERIC Educational Resources Information Center

    Falco, Mathea

    From the mid-1960s until 1980, adolescent drug use rose sharply. Although use has declined somewhat since, adolescent cocaine use remains at peak levels, and crack presents a major threat. Treatment for compulsive drug or alcohol use is needed by 5 to 15 percent of the teenagers who experiment with drugs and alcohol. Drug abuse experts now believe…

  6. A Longitudinal Examination of Physiological Regulation in Cocaine-Exposed Infants across the First 7 Months of Life

    ERIC Educational Resources Information Center

    Schuetze, Pamela; Eiden, Rina D.; Edwards, Ellen P.

    2009-01-01

    This study examined the association between prenatal exposure to cocaine and physiological regulation across the first 7 months of age. Measures of respiratory sinus arrhythmia (RSA) were obtained from 169 (82 cocaine-exposed and 87 nonexposed) infants during baseline periods at 1 month and 7 months of age and during tasks designed to elicit…

  7. Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys.

    PubMed

    Wang, Zhixia; Woolverton, William L

    2009-02-01

    Histamine H1 receptor antagonists can be sedating and have behavioral effects, including reinforcing and discriminative stimulus effects in non-humans, that predict abuse liability. Previous research has suggested that antihistamines can enhance the effects of some drugs of abuse. We have reported a synergistic interaction between cocaine and diphenhydramine (DPH) in a self-administration assay with monkeys. The present study was designed to extend those findings to other combinations of cocaine and DPH, and to the mixture of cocaine and another H1-antihistamine, pyrilamine. Rhesus monkeys were prepared with chronic i.v. catheters and allowed to self-administer cocaine, DPH or pyrilamine alone or as mixtures under a progressive-ratio schedule of reinforcement. Cocaine, DPH and pyrilamine alone maintained self-administration and cocaine was the stronger reinforcer. When cocaine was combined with DPH or pyrilamine in a 1:1, 1:2 or 2:1 ratio of the ED(50)s, the combinations were super-additive as reinforcers. Reinforcing strength of the combinations was greater than that of the antihistamines alone but not greater than cocaine. The data support the prediction that the combination of cocaine and histamine H1 receptor antagonists could have enhanced potential for abuse relative to either drug alone. The interaction may involve dopamine systems in the CNS. PMID:18930758

  8. Psychiatric comorbidity in a sample of cocaine-dependent outpatients seen in the Community of Madrid drug addiction care network.

    PubMed

    Martínez-Gras, Isabel; Ferre Navarrete, Francisco; Pascual Arriazu, Jesús; Peñas Pascual, José; de Iceta Ruiz de Gauna, Mariano; Fraguas Herráez, David; Rubio Valladolid, Gabriel

    2016-03-02

    The objective of this study was to estimate the current prevalence of psychiatric disorders in cocaine-dependent patients who attend different treatment centres in the Community of Madrid. A prospective multicentre study was used, and a total of 197 cocaine-dependent subjects were assessed. The assessment instrument used for diagnosis was the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). The main findings of this study were a high prevalence of psychiatric comorbidity in cocaine-dependent patients seeking treatment (64.0%). The most common Non Substance Use Disorders found were attention-deficit/hyperactivity Disorders (34.5%) and depressive disorders (13.7%). The most common Substance Use Disorder was alcohol dependence (28.4%). Cocaine-dependent patients who had a depressive disorder and were alcohol dependent presented a more severe clinical profile and a higher degree of psychopathology, measured using different assessment tools, than the patients who were only cocaine dependent. These data suggest that the presence of psychiatric comorbidity could constitute a risk factor associated with the severity of cocaine dependence. The clinical heterogeneity found also indicates the need to search for individualised treatments that more specifically fit the needs of this population.

  9. Psychiatric comorbidity in a sample of cocaine-dependent outpatients seen in the Community of Madrid drug addiction care network.

    PubMed

    Martínez-Gras, Isabel; Ferre Navarrete, Francisco; Pascual Arriazu, Jesús; Peñas Pascual, José; de Iceta Ruiz de Gauna, Mariano; Fraguas Herráez, David; Rubio Valladolid, Gabriel

    2016-01-01

    The objective of this study was to estimate the current prevalence of psychiatric disorders in cocaine-dependent patients who attend different treatment centres in the Community of Madrid. A prospective multicentre study was used, and a total of 197 cocaine-dependent subjects were assessed. The assessment instrument used for diagnosis was the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV). The main findings of this study were a high prevalence of psychiatric comorbidity in cocaine-dependent patients seeking treatment (64.0%). The most common Non Substance Use Disorders found were attention-deficit/hyperactivity Disorders (34.5%) and depressive disorders (13.7%). The most common Substance Use Disorder was alcohol dependence (28.4%). Cocaine-dependent patients who had a depressive disorder and were alcohol dependent presented a more severe clinical profile and a higher degree of psychopathology, measured using different assessment tools, than the patients who were only cocaine dependent. These data suggest that the presence of psychiatric comorbidity could constitute a risk factor associated with the severity of cocaine dependence. The clinical heterogeneity found also indicates the need to search for individualised treatments that more specifically fit the needs of this population. PMID:26990385

  10. Effects of chronic binge-like ethanol consumption on cocaine self-administration in rhesus monkeys

    PubMed Central

    Czoty, Paul W.

    2015-01-01

    Background Most cocaine abusers also abuse alcohol, but little is known about interactions that promote co-abuse. These experiments in rhesus monkeys determined the effects of >8 weeks of ethanol (EtOH) consumption on cocaine self-administration (n=6), effects of dopamine (DA) receptor antagonists on cocaine reinforcement (n=3–4 per drug) and the ability of the D2-like DA receptor agonist quinpirole to elicit yawning (n=3). Methods Monkeys self-administered cocaine (0.0–1.0 mg/kg/injection, i.v.) under a 300-second fixed-interval schedule and the above-listed variables were measured before EtOH exposure. Next, monkeys consumed a sweetened, 4% EtOH solution in the home cage under binge-like conditions: one hour, 5 days/week with daily intake equaling 2.0 g/kg EtOH. After approximately 8 weeks, measures were re-determined, then EtOH drinking was discontinued. Finally, acute effects of EtOH on cocaine self-administration were determined by infusing EtOH (0.0–1.0 g/kg. i.v.) prior to cocaine self-administration sessions (n=4). Results In 5 of 6 monkeys, EtOH drinking increased self-administration of low cocaine doses but did not alter reinforcing effects of higher doses. Self-administration returned to baseline after EtOH access was terminated (n=3). Effects of DA receptor antagonists on cocaine self-administration were not consistently altered after EtOH consumption, but the ability of quinpirole to induce yawning was enhanced in 2 of 3 monkeys. Acute EtOH infusions only decreased self-administration of lower cocaine doses. Conclusions Taken together, the data suggest that long-term EtOH exposure can increase sensitivity to cocaine, possibly by increasing D3 receptor sensitivity. Data do not support a role for acute pharmacological interactions in promoting cocaine/EtOH co-abuse. PMID:26048636

  11. Differentiating the rapid actions of cocaine

    PubMed Central

    Wise, Roy A.; Kiyatkin, Eugene A.

    2011-01-01

    The subjective effects of intravenous cocaine are felt almost immediately, and this immediacy plays an important part in the drug’s rewarding impact. The primary rewarding effect of cocaine involves blockade of dopamine reuptake; however, the onset of this action is too late to account for the drug’s initial effects. Recent studies suggest that cocaine-predictive cues — including peripheral interoceptive cues generated by cocaine itself — come to cause more direct and earlier reward signalling by activating excitatory inputs to the dopamine system. The conditioned activation of the dopamine system by cocaine-predictive cues offers a new target for potential addiction therapies. PMID:21633381

  12. Multiple Gastrointestinal Complications of Crack Cocaine Abuse

    PubMed Central

    Carlin, Neal; Nguyen, Nhat; DePasquale, Joseph R.

    2014-01-01

    Cocaine and its alkaloid free base “crack-cocaine” have long since been substances of abuse. Drug abuse of cocaine via oral, inhalation, intravenous, and intranasal intake has famously been associated with a number of medical complications. Intestinal ischemia and perforation remain the most common manifestations of cocaine associated gastrointestinal disease and have historically been associated with oral intake of cocaine. Here we find a rare case of two relatively uncommon gastrointestinal complications of hemorrhage and pancreatitis presenting within a single admission in a chronic crack cocaine abuser. PMID:24839446

  13. The epidemiology of cocaine use in Spain.

    PubMed

    Barrio Anta, G; Vicente Orta, J; Bravo Portela, M J; de la Fuente de Hoz, L

    1993-12-01

    Trends and patterns of cocaine use in Spain are described with the aid of different information sources such as population surveys, the State Information System on Drug Abuse, and anthropological studies. In recent years the magnitude of cocaine supply indicators has increased greatly. High levels of last-month prevalence of cocaine use have been detected among the general population--consistently higher than those for heroin-- and cocaine consumption among heroin users has increased. Although the frequency of some health problems related to cocaine use--treatment admissions, hospital emergency admissions--has increased, it is still 30 times less than for heroin. Various hypotheses to explain these discrepancies are discussed.

  14. Drug smuggling using clothing impregnated with cocaine.

    PubMed

    McDermott, Seán D; Power, John D

    2005-11-01

    A case study is presented where a woman travelling from South America to the Republic of Ireland was detained at Dublin Airport and articles of clothing she had in her luggage were found to be impregnated with cocaine. The study shows that the amount of powder recovered from the garments was approximately 14% of the total weight of the garments. The cocaine was in the form of cocaine hydrochloride and the purity was approximately 80%. An examination of the garments under filtered light highlighted the areas exposed to cocaine and indicated that the method of impregnation was by pouring liquid containing cocaine onto the clothing.

  15. A novel monoclonal antibody specific for cocaine.

    PubMed

    Nakayama, Hiroshi; Kenjyou, Noriko; Shigetoh, Nobuyuki

    2013-08-01

    Detection systems for the illegal drug cocaine need to have a high sensitivity and specificity for cocaine and to be relatively easy to use. In the current study, a monoclonal antibody (MAb) with a high specificity for cocaine was produced. Enzyme-linked immunosorbent assay and fluorescence quenching immunoassay were used to screen the hybridomas. The MAb S27Y (IgG1) was shown to be sensitive and specific for cocaine and quenched fluorescence. Thus, S27Y has the potential to be used in screening assays for the rapid and sensitive detection of cocaine. PMID:23909419

  16. Computational Design of Non-natural Sugar Alcohols to Increase Thermal Storage Density: Beyond Existing Organic Phase Change Materials.

    PubMed

    Inagaki, Taichi; Ishida, Toyokazu

    2016-09-14

    Thermal storage, a technology that enables us to control thermal energy, makes it possible to reuse a huge amount of waste heat, and materials with the ability to treat larger thermal energy are in high demand for energy-saving societies. Sugar alcohols are now one promising candidate for phase change materials (PCMs) because of their large thermal storage density. In this study, we computationally design experimentally unknown non-natural sugar alcohols and predict their thermal storage density as a basic step toward the development of new high performance PCMs. The non-natural sugar alcohol molecules are constructed in silico in accordance with the previously suggested molecular design guidelines: linear elongation of a carbon backbone, separated distribution of OH groups, and even numbers of carbon atoms. Their crystal structures are then predicted using the random search method and first-principles calculations. Our molecular simulation results clearly demonstrate that the non-natural sugar alcohols have potential ability to have thermal storage density up to ∼450-500 kJ/kg, which is significantly larger than the maximum thermal storage density of the present known organic PCMs (∼350 kJ/kg). This computational study suggests that, even in the case of H-bonded molecular crystals where the electrostatic energy contributes mainly to thermal storage density, the molecular distortion and van der Waals energies are also important factors to increase thermal storage density. In addition, the comparison between the three eight-carbon non-natural sugar alcohol isomers indicates that the selection of preferable isomers is also essential for large thermal storage density. PMID:27505107

  17. Computational Design of Non-natural Sugar Alcohols to Increase Thermal Storage Density: Beyond Existing Organic Phase Change Materials.

    PubMed

    Inagaki, Taichi; Ishida, Toyokazu

    2016-09-14

    Thermal storage, a technology that enables us to control thermal energy, makes it possible to reuse a huge amount of waste heat, and materials with the ability to treat larger thermal energy are in high demand for energy-saving societies. Sugar alcohols are now one promising candidate for phase change materials (PCMs) because of their large thermal storage density. In this study, we computationally design experimentally unknown non-natural sugar alcohols and predict their thermal storage density as a basic step toward the development of new high performance PCMs. The non-natural sugar alcohol molecules are constructed in silico in accordance with the previously suggested molecular design guidelines: linear elongation of a carbon backbone, separated distribution of OH groups, and even numbers of carbon atoms. Their crystal structures are then predicted using the random search method and first-principles calculations. Our molecular simulation results clearly demonstrate that the non-natural sugar alcohols have potential ability to have thermal storage density up to ∼450-500 kJ/kg, which is significantly larger than the maximum thermal storage density of the present known organic PCMs (∼350 kJ/kg). This computational study suggests that, even in the case of H-bonded molecular crystals where the electrostatic energy contributes mainly to thermal storage density, the molecular distortion and van der Waals energies are also important factors to increase thermal storage density. In addition, the comparison between the three eight-carbon non-natural sugar alcohol isomers indicates that the selection of preferable isomers is also essential for large thermal storage density.

  18. Alcohol use dependence in fragile X syndrome

    PubMed Central

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-01-01

    Summary Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures. PMID:27672544

  19. Alcohol use dependence in fragile X syndrome.

    PubMed

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-08-01

    Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures. PMID:27672544

  20. Alcohol use dependence in fragile X syndrome

    PubMed Central

    Salcedo-Arellano, María J; Lozano, Reymundo; Tassone, Flora; Hagerman, Randi J; Saldarriaga, Wilmar

    2016-01-01

    Summary Alcohol use disorders (AUDs) have been reported in a limited number of individuals with cognitive impairment but rarely in those with fragile X syndrome (FXS). However, in Colombia, culturally, alcohol consumption is very common. Here, we report eight cases of patients with FXS who have frequent alcohol consumption in Ricaurte, Colombia. Some of these patients have also used tobacco and illegal substances, including cocaine, which use has not been previously reported in those with FXS. Alcohol and substance use dependence is associated with exacerbation of their behavioral problems, such as increased impulsivity and aggression, as well as of medical problems such as an increased frequency of seizures.

  1. Reliability of the Timeline Followback for cocaine, cannabis, and cigarette use.

    PubMed

    Robinson, Sean M; Sobell, Linda Carter; Sobell, Mark B; Leo, Gloria I

    2014-03-01

    The Timeline Followback (TLFB), a retrospective calendar-based measure of daily substance use, was initially developed to obtain self-reports of alcohol use. Since its inception it has undergone extensive evaluation across diverse populations and is considered the most psychometrically sound self-report measure of drinking. Although the TLFB has been extended to other behaviors, its psychometric evaluation with other addictive behaviors has not been as extensive as for alcohol use. The present study evaluated the test-retest reliability of the TLFB for cocaine, cannabis, and cigarette use for participants recruited from outpatient alcohol and drug treatment programs and the general community across intervals ranging from 30 to 360 days prior to the interview. The dependent measure for cigarette smokers and cannabis users was daily use of cigarettes and joints, respectively, and for cocaine users it was a "Yes" or "No" regarding cocaine use for each day. The TLFB was administered in different formats for different drug types. Different interviewers conducted the two interviews. The TLFB collected highly reliable information about participants' daily use of cocaine, cannabis, and cigarettes from 30, 90, to 360 days prior to the interview. Findings from this study not only suggest that shorter time intervals (e.g., 90 days) can be used with little loss of accuracy, but also add to the growing literature that the TLFB can be used with confidence to collect psychometrically sound information about substance use (i.e., cocaine, cannabis, cigarettes) other than alcohol in treatment- and nontreatment-seeking populations for intervals from ranging up to 12 months prior to the interview.

  2. Cocaine use and the breastfeeding mother.

    PubMed

    Jones, Wendy

    2015-01-01

    Cocaine is the second most commonly used illicit drug. Use in pregnancy and breastfeeding may have severe consequences for the baby due to its pharmacokinetic properties. Midwives need to be aware of the prolonged action of cocaine and be alert to the possibility of cocaine toxicity if a baby is excessively irritable and tachycardic. Euphoric highs are brief but breast milk and urine remain positive for long periods. Infant urine following exposure to cocaine via breast milk may remain positive for up to 60 hours. Mothers who snort cocaine should pump and dump breast milk for 24-48 hours. Passive inhalation of crack cocaine smoke may also result in infants with positive toxicology screens. Cocaine powder should never be applied to the nipples of breastfeeding mothers. PMID:26310088

  3. Design and synthesis of copper-cobalt catalysts for the selective conversion of synthesis gas to ethanol and higher alcohols.

    PubMed

    Prieto, Gonzalo; Beijer, Steven; Smith, Miranda L; He, Ming; Au, Yuen; Wang, Zi; Bruce, David A; de Jong, Krijn P; Spivey, James J; de Jongh, Petra E

    2014-06-16

    Combining quantum-mechanical simulations and synthesis tools allows the design of highly efficient CuCo/MoO(x) catalysts for the selective conversion of synthesis gas (CO+H2) into ethanol and higher alcohols, which are of eminent interest for the production of platform chemicals from non-petroleum feedstocks. Density functional theory calculations coupled to microkinetic models identify mixed Cu-Co alloy sites, at Co-enriched surfaces, as ideal for the selective production of long-chain alcohols. Accordingly, a versatile synthesis route is developed based on metal nanoparticle exsolution from a molybdate precursor compound whose crystalline structure isomorphically accommodates Cu(2+) and Co(2+) cations in a wide range of compositions. As revealed by energy-dispersive X-ray nanospectroscopy and temperature-resolved X-ray diffraction, superior mixing of Cu and Co species promotes formation of CuCo alloy nanocrystals after activation, leading to two orders of magnitude higher yield to high alcohols than a benchmark CuCoCr catalyst. Substantiating simulations, the yield to high alcohols is maximized in parallel to the CuCo alloy contribution, for Co-rich surface compositions, for which Cu phase segregation is prevented.

  4. Effects of Sleep Deprivation on Brain Bioenergetics, Sleep, and Cognitive Performance in Cocaine-Dependent Individuals

    PubMed Central

    Trksak, George H.; Bracken, Bethany K.; Jensen, J. Eric; Plante, David T.; Penetar, David M.; Tartarini, Wendy L.; Maywalt, Melissa A.; Dorsey, Cynthia M.; Renshaw, Perry F.; Lukas, Scott E.

    2013-01-01

    In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent [31]P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, [31]P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse. PMID:24250276

  5. Effects of sleep deprivation on brain bioenergetics, sleep, and cognitive performance in cocaine-dependent individuals.

    PubMed

    Trksak, George H; Bracken, Bethany K; Jensen, J Eric; Plante, David T; Penetar, David M; Tartarini, Wendy L; Maywalt, Melissa A; Dorsey, Cynthia M; Renshaw, Perry F; Lukas, Scott E

    2013-01-01

    In cocaine-dependent individuals, sleep is disturbed during cocaine use and abstinence, highlighting the importance of examining the behavioral and homeostatic response to acute sleep loss in these individuals. The current study was designed to identify a differential effect of sleep deprivation on brain bioenergetics, cognitive performance, and sleep between cocaine-dependent and healthy control participants. 14 healthy control and 8 cocaine-dependent participants experienced consecutive nights of baseline, total sleep deprivation, and recovery sleep in the research laboratory. Participants underwent ³¹P magnetic resonance spectroscopy (MRS) brain imaging, polysomnography, Continuous Performance Task, and Digit Symbol Substitution Task. Following recovery sleep, ³¹P MRS scans revealed that cocaine-dependent participants exhibited elevated global brain β-NTP (direct measure of adenosine triphosphate), α-NTP, and total NTP levels compared to those of healthy controls. Cocaine-dependent participants performed worse on the Continuous Performance Task and Digit Symbol Substitution Task at baseline compared to healthy control participants, but sleep deprivation did not worsen cognitive performance in either group. Enhancements of brain ATP levels in cocaine dependent participants following recovery sleep may reflect a greater impact of sleep deprivation on sleep homeostasis, which may highlight the importance of monitoring sleep during abstinence and the potential influence of sleep loss in drug relapse. PMID:24250276

  6. Effects of cocaine on simple reaction times and sensory thresholds in baboons.

    PubMed Central

    Hienz, R D; Spear, D J; Bowers, D A

    1994-01-01

    The effects of chronic, daily administration of cocaine on auditory and visual reaction times and thresholds were studied in baboons. Single intramuscular injections of cocaine hydrochloride (0.1 to 5.6 mg/kg) were given once daily for periods of 10 to 25 days, and were followed immediately by psychophysical tests designed to assess cocaine's effects on simple reaction times as on auditory and visual threshold functions. Consistent reductions in reaction times were frequently observed over the cocaine dose range of 0.32 to 1.0 mg/kg; at higher doses, either decreases or increases in reaction times were observed, depending upon the animal. Lowered reaction times generally occurred immediately following the 1st day's cocaine injection, and continued through all subsequent days during the dose administration period, suggesting little development of tolerance or sensitivity to these reaction-time effects. Reaction-time decreases showed a U-shaped dose-effect function. The greatest decreases in reaction times occurred from 0.32 to 1.0 mg/kg, and produced an average reaction-time decrease of 10 to 12%. Concurrently measured auditory and visual thresholds showed no systematic changes as a function of cocaine dose. Pausing was observed during performance of the psychophysical tasks, with the length of total session pause times being directly related to cocaine dose. PMID:8169572

  7. Psychopathology and Special Education Enrollment in Children with Prenatal Cocaine Exposure

    PubMed Central

    Levine, Todd P.; Lester, Barry; Lagasse, Linda; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Whitaker, Toni M.; Higgins, Rosemary; Hammond, Jane; Roberts, Mary B.

    2012-01-01

    Objective This study evaluated how enrollment in special education services in 11 year old children relates to prenatal cocaine exposure, psychopathology, and other risk factors. Method Participants were 498 children enrolled in The Maternal Lifestyle Study, a prospective, longitudinal, multisite study examining outcomes of children with prenatal cocaine exposure. Logistic regression was used to examine the effect of prenatal cocaine exposure and psychopathology on enrollment in an individualized education plan (a designation specific to children with special education needs), with environmental, maternal, and infant medical variables as covariates. Results Prenatal cocaine exposure, an interaction of prenatal cocaine exposure and Oppositional Defiant Disorder, child Attention Deficit Hyperactivity Disorder, parent-reported internalizing behaviors, and teacher-reported externalizing behaviors, predicted enrollment in an individualized education plan. Other statistically significant variables in the model were male gender, low birth weight, being small for gestational age, white race, caregiver change, low socio-economic status, low child intelligence quotient, caregiver depression, and prenatal marijuana exposure. Conclusions Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan with adjustment for covariates. Psychopathology also predicted this special education outcome, in combination with and independent of prenatal cocaine exposure. PMID:22487696

  8. Putting cocaine use and cocaine-associated cardiac arrhythmias into epidemiological and clinical perspective

    PubMed Central

    Wood, David M; Dargan, Paul I

    2010-01-01

    This is the first article in a series of three articles on cocaine-related cardiac arrhythmias, following on from the 2008 British Pharmacological Society Winter Meeting Clinical Section Symposium entitled ‘Cocaine induced cardiac arrhythmias – from ion channel to clinical treatment’. We will summarize the epidemiology of cocaine use across the world and in particular will focus on UK, Europe and US use prevalence data. We will discuss the acute cardiac and non-cardiac toxicity associated with cocaine and highlight the lack of data on the true UK prevalence of acute cocaine toxicity and on the incidence of cocaine-related cardiac arrhythmias. PMID:20573079

  9. Intravenous Cocaine Priming Reinstates Cocaine-Induced Conditioned Place Preference

    ERIC Educational Resources Information Center

    Lombas, Andres S.; Freeman, Kevin B.; Roma, Peter G.; Riley, Anthony L.

    2007-01-01

    Separate groups of rats underwent an unbiased conditioned place preference (CPP) procedure involving alternate pairings of distinct environments with intravenous (IV) injections of cocaine (0.75 mg/kg) or saline immediately or 15 min after injection. A subsequent extinction phase consisted of exposure to both conditioning environments preceded by…

  10. The effects of a humanized recombinant anti-cocaine monoclonal antibody on the disposition of cocaethylene in mice.

    PubMed

    Wetzel, Hanna N; Tabet, Michael R; Ball, William J; Norman, Andrew B

    2014-12-01

    The chimeric human/mouse anti-cocaine monoclonal antibody (mAb) 2E2 and its further humanized variant h2E2 have been reported to sequester a significant portion of cocaine in plasma and decrease cocaine concentrations in the brain in mice and rats. However, many cocaine users co-abuse alcohol, leading to the formation of the centrally active metabolite cocaethylene. This potentially compromises the efficacy of a cocaine-specific immunotherapy. Because h2E2 has high affinity for cocaethylene as well as cocaine, the ability of h2E2 to prevent cocaethylene entry into the brain was investigated. Mice were infused with h2E2 (1.6 μmol/kg i.v.) or vehicle and after one hour were injected with cocaethylene fumarate (1.2 μmol/kg i.v.). At times from 45 s to 60 min, brain and plasma were collected and cocaethylene concentrations were measured using GC/MS. In control mice, a two-compartment pharmacokinetic model generated values for cocaethylene distribution and terminal elimination half-lives of 0.5 and 8.1 min respectively. Initial plasma cocaethylene concentrations increased 13-fold from controls in the presence of h2E2. In brain, h2E2 produced a 92% decrease in the area under the time-concentration curve for cocaethylene. The pharmacokinetics of h2E2 was also characterized in detail. A three-compartment model resolved an initial distribution half-life of 4.4 min and a second distribution half-life of 4.2 h, and a terminal elimination half-life of 7.8 days. The ability of h2E2 to protect the brain from both cocaine and cocaethylene predicts that the clinical efficacy of h2E2 will be retained in cocaine users who co-abuse alcohol. PMID:25445957

  11. The effects of a humanized recombinant anti-cocaine monoclonal antibody on the disposition of cocaethylene in mice

    PubMed Central

    Wetzel, Hanna N.; Tabet, Michael R.; Ball, William J.; Norman, Andrew B.

    2014-01-01

    The chimeric human/mouse anti-cocaine monoclonal antibody (mAb) 2E2 and its further humanized variant h2E2 have been reported to sequester a significant portion of cocaine in plasma and decrease cocaine concentrations in the brain in mice and rats. However, many cocaine users co-abuse alcohol, leading to the formation of the centrally active metabolite cocaethylene. This potentially compromises the efficacy of a cocaine-specific immunotherapy. Because h2E2 has high affinity for cocaethylene as well as cocaine, the ability of h2E2 to prevent cocaethylene entry into the brain was investigated. Mice were infused with h2E2 (1.6 µmol/kg i.v.) or vehicle and after one hour were injected with cocaethylene fumarate (1.2 µmol/kg i.v.). At times from 45 seconds to 60 minutes, brain and plasma were collected and cocaethylene concentrations were measured using GC/MS. In control mice, a two-compartment pharmacokinetic model generated values for cocaethylene distribution and terminal elimination half-lives of 0.5 and 8.1 min respectively. Initial plasma cocaethylene concentrations increased 13-fold from controls in the presence of h2E2. In brain, h2E2 produced a 92% decrease in the area under the time-concentration curve for cocaethylene. The pharmacokinetics of h2E2 were also characterized in detail. A three-compartment model resolved an initial distribution half-life of 4.4 minutes and a second distribution half-life of 4.2 hours, and a terminal elimination half-life of 7.8 days. The ability of h2E2 to protect the brain from both cocaine and cocaethylene predicts that the clinical efficacy of h2E2 will be retained in cocaine users who co-abuse alcohol. PMID:25445957

  12. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    PubMed

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.

  13. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    PubMed

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction. PMID:20680706

  14. Prenatal cocaine effects on brain structure in early infancy.

    PubMed

    Grewen, Karen; Burchinal, Margaret; Vachet, Clement; Gouttard, Sylvain; Gilmore, John H; Lin, Weili; Johns, Josephine; Elam, Mala; Gerig, Guido

    2014-11-01

    Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life. PMID:24999039

  15. Prenatal cocaine effects on brain structure in early infancy.

    PubMed

    Grewen, Karen; Burchinal, Margaret; Vachet, Clement; Gouttard, Sylvain; Gilmore, John H; Lin, Weili; Johns, Josephine; Elam, Mala; Gerig, Guido

    2014-11-01

    Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life.

  16. Sex differences in behavioral and PKA cascade responses to repeated cocaine administration.

    PubMed

    Zhou, Luyi; Sun, Wei-Lun; Weierstall, Karen; Minerly, Ana Christina; Weiner, Jan; Jenab, Shirzad; Quinones-Jenab, Vanya

    2016-10-01

    Previous studies have shown sex different patterns in behavioral responses to cocaine. Here, we used between-subject experiment design to study whether sex differences exist in the development of behavioral sensitization and tolerance to repeated cocaine, as well as the role of protein kinase A (PKA) signaling cascade in this process. Ambulatory and rearing responses were recorded in male and female rats after 1 to 14 days of administration of saline or cocaine (15 mg/kg; ip). Correspondent PKA-associated signaling in the nucleus accumbens (NAc) and caudate-putamen (CPu) was measured at each time point. Our results showed that females exhibited higher cocaine-induced behavioral responses and developed behavioral sensitization and tolerance faster than males. Whereas females developed behavioral sensitization to cocaine after 2 days and tolerance after 14 days, male rats developed sensitization after 5 days. In addition, cocaine induced a sexual dimorphic pattern in the progression of neuronal adaptations on the PKA cascade signaling in region (NAc vs. CPu) and time (days of cocaine administration)-dependent manners. In general, more PKA signaling cascade changes were found in the NAc of males on day 5 and in the CPu of females with repeated cocaine injection. In addition, in females, behavioral activities positively correlated with FosB levels in the NAc and CPu and negatively correlated with Cdk5 and p35 in the CPu, while no correlation was observed in males. Our studies suggest that repeated cocaine administration induced different patterns of behavioral and molecular responses in the PKA cascade in male and female rats. PMID:27553823

  17. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    PubMed Central

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  18. The economical production of alcohol fuels from coal-derived synthesis gas: Case studies, design, and economics

    SciTech Connect

    1995-10-01

    This project is a combination of process simulation and catalyst development aimed at identifying the most economical method for converting coal to syngas to linear higher alcohols to be used as oxygenated fuel additives. There are two tasks. The goal of Task 1 is to discover, study, and evaluate novel heterogeneous catalytic systems for the production of oxygenated fuel enhancers from synthesis gas, and to explore, analytically and on the bench scale, novel reactor and process concepts for use in converting syngas to liquid fuel products. The goal of Task 2 is to simulate, by computer, energy efficient and economically efficient processes for converting coal to energy (fuel alcohols and/or power). The primary focus is to convert syngas to fuel alcohols. This report contains results from Task 2. The first step for Task 2 was to develop computer simulations of alternative coal to syngas to linear higher alcohol processes, to evaluate and compare the economics and energy efficiency of these alternative processes, and to make a preliminary determination as to the most attractive process configuration. A benefit of this approach is that simulations will be debugged and available for use when Task 1 results are available. Seven cases were developed using different gasifier technologies, different methods for altering the H{sub 2}/CO ratio of the syngas to the desired 1.1/1, and with the higher alcohol fuel additives as primary products and as by-products of a power generation facility. Texaco, Shell, and Lurgi gasifier designs were used to test gasifying coal. Steam reforming of natural gas, sour gas shift conversion, or pressure swing adsorption were used to alter the H{sub 2}/CO ratio of the syngas. In addition, a case using only natural gas was prepared to compare coal and natural gas as a source of syngas.

  19. Polypeptide Functional Surface for the Aptamer Immobilization: Electrochemical Cocaine Biosensing.

    PubMed

    Bozokalfa, Guliz; Akbulut, Huseyin; Demir, Bilal; Guler, Emine; Gumus, Z Pınar; Odaci Demirkol, Dilek; Aldemir, Ebru; Yamada, Shuhei; Endo, Takeshi; Coskunol, Hakan; Timur, Suna; Yagci, Yusuf

    2016-04-01

    Electroanalytical technologies as a beneficial subject of modern analytical chemistry can play an important role for abused drug analysis which is crucial for both legal and social respects. This article reports a novel aptamer-based biosensing procedure for cocaine analysis by combining the advantages of aptamers as selective recognition elements with the well-known advantages of biosensor systems such as the possibility of miniaturization and automation, easy fabrication and modification, low cost, and sensitivity. In order to construct the aptasensor platform, first, polythiophene bearing polyalanine homopeptide side chains (PT-Pala) was electrochemically coated onto the surface of an electrode and then cocaine aptamer was attached to the polymer via covalent conjugation chemistry. The stepwise modification of the surface was confirmed by electrochemical characterization. The designed biosensing system was applied for the detection of cocaine and its metabolite, benzoylecgonine (BE), which exhibited a linear correlation in the range from 2.5 up to 10 nM and 0.5 up to 50 μM for cocaine and BE, respectively. In order to expand its practical application, the proposed method was successfully tested for the analysis of synthetic biological fluids. PMID:26928030

  20. Probing the Effects of Hapten Stability on Cocaine Vaccine Immunogenicity

    PubMed Central

    Cai, Xiaoqing; Whitfield, Timothy; Moreno, Amira Y.; Grant, Yanabel; Hixon, Mark S.; Koob, George F.; Janda, Kim D.

    2013-01-01

    Judicious hapten design has been shown to be of importance when trying to generate a viable vaccine against a drug of abuse. Hapten design has typically been predicated upon faithfully emulating the unique chemical architecture that each drug presents. However, the need for drug-hapten congruency may also compromise vaccine immunogenicity if the drug-hapten conjugate possesses epitope instability. There has been no systematic study on the impact of hapten stability as it relates to vaccine immunogenicity. As a starting point, we have probed the stability of a series of cocaine haptens through varying several of its structural elements, including functionality at the C2-position, the nature of the linker and its site of attachment. Accordingly, a hydrolytic stability profile of four cocaine haptens (GNNA, GNNS, GNE and GNC) was produced and these results were compared through each hapten’s immunological properties, which were generated via active vaccination. From this group of four, three of the haptens, GNE, GNNA and GNC were further examined in an animal behavioral model, and findings here were again measured in relationship to hapten stability. We demonstrate a corresponding relationship between the half-life of the hapten and its immunogenicity, wherein haptens presenting a fully representative cocaine framework elicited higher concentrations of cocaine-specific IgG in sera and also conferred better protection against cocaine-induced locomotor activity. Our results indicate that hapten half-life plays an important role in vaccine immunogenicity and this in turn can impact animal behavioral effects when challenged with a drug of abuse. PMID:23927436

  1. Effect of intrauterine cocaine exposure on respiratory distress syndrome in very low birthweight infants.

    PubMed Central

    Beeram, M. R.; Abedin, M.; Young, M.; Leftridge, C.; Dhanireddy, R.

    1994-01-01

    To evaluate the effect of intrauterine cocaine exposure on lung maturity of very low birthweight infants, the medical records of all infants with birthweight < 1500 g born between January 1989 and December 1990 at DC General Hospital were reviewed. Infants with conditions known to cause lung maturity, severe congenital anomalies, proven early sepsis, and birthweight > or = 500 g were excluded. A total of 69 infants were included in the study. Chest roentgenograms of these infants were evaluated by a pediatric radiologist, who was unaware of the infant's medical course, for evidence of respiratory distress syndrome (RDS), and radiological findings were correlated with clinical signs. Forty infants were exposed to cocaine in utero (cocaine group) and 29 were not exposed (noncocaine group). African-American ethnicity, pregnancy-induced hypertension, prolonged rupture of membranes, and alcohol use were similar in both groups. Tobacco use among cocaine group mothers was higher (42.5% versus 13.8%; P = .01). Gestational age (28.3 +/- 2.8 versus 28.3 +/- 3 weeks), birthweight (966 +/- 282 versus 1059 +/- 295 g), male gender, and Apgar scores were similar in both groups. Thirty (75%) infants in the cocaine group developed RDS compared with 19 (66%) in the noncocaine group (P > .05). Using multiple logistic regression analysis and controlling for smoking, alcohol use, and prolonged rupture of membranes (24 to 72 hours), the incidence of RDS between the groups remained statistically insignificant. We conclude that intrauterine cocaine exposure does not alter the incidence of RDS in very low birthweight infants. PMID:8046765

  2. Adverse health consequences of cocaine abuse.

    PubMed Central

    Cregler, L. L.

    1989-01-01

    Cocaine creates a strong physical addiction and is becoming recognized as one of the most dangerous illicit drugs abused today. The myth is that cocaine is harmless and nonaddictive. An estimated 30 million Americans have used cocaine, but the number may be as high as 40 million. Five to six million individuals are compulsive users. A review of the current literature revealed multiple reports of acute myocardial infarction and cerebrovascular accident with a temporal relation to cocaine use. Cocaine has also been associated with acute rupture of the aorta, cardiac arrhythmia, and sudden death. Cocaine has multisystem toxicity involving neurologic, psychiatric, obstetric, pulmonary, dermatologic, and gastrointestinal systems. The dopamine depletion hypothesis may explain why cocaine is repeatedly administered; cocaine produces a transient increase in synaptic dopamine. Alterations in dopamine neurotransmission may be responsible for the development of compulsive use patterns. When cocaine use becomes compulsive, psychosocial dysfunction, deviant behaviors, and a wide spectrum of social, financial, and family problems invariably result. Addiction, major medical complications, and death are true hazards of cocaine use. PMID:2657079

  3. Multiple faces of BDNF in cocaine addiction

    PubMed Central

    Li, Xuan; Wolf, Marina E.

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) has been found to play roles in many types of plasticity including drug addiction. Here we focus on rodent studies over the past two decades that have demonstrated diverse roles of BDNF in models of cocaine addiction. First, we will provide an overview of studies showing that cocaine exposure alters (and generally increases) BDNF levels in reward-related regions including the ventral tegmental area, nucleus accumbens, prefrontal cortex, and amygdala. Then we will review evidence that BDNF contributes to behavioral changes in animal models of cocaine addiction, focusing on conditioned place preference, behavioral sensitization, maintenance and reinstatement of self-administration, and incubation of cocaine craving. Last, we will review the role of BDNF in synaptic plasticity, particularly as it relates to plasticity of AMPA receptor transmission after cocaine exposure. We conclude that BDNF regulates cocaine-induced behaviors in a highly complex manner that varies depending on the brain region (and even among different cell types within the same brain region), the nature of cocaine exposure, and the “addiction phase” examined (e.g., acquisition vs maintenance; early vs late withdrawal). These complexities make BDNF a daunting therapeutic target for treating cocaine addiction. However, recent clinical evidence suggests that the serum BDNF level may serve as a biomarker in cocaine addicts to predict future relapse, providing an alternative direction for exploring BDNF’s potential relevance to treating cocaine addiction. PMID:25449839

  4. Simultaneous pharmacokinetic modeling of cocaine and its metabolites, norcocaine and benzoylecgonine, after intravenous and oral administration in rats.

    PubMed

    Sun, L; Lau, C E

    2001-09-01

    To accurately assess the mechanism of involvement of the active metabolite norcocaine in the effects of oral cocaine, it is essential to determine the rate and extent of the formation of norcocaine. Although this study was designed specifically for this aim, it was also of interest to characterize the metabolite kinetics of benzoylecgonine for comparative purpose. We first characterized the pharmacokinetics of cocaine, norcocaine, and benzoylecgonine by the i.v. route of administration; all three drugs decayed biexponentially. These pharmacokinetic estimates were then used for determination of the formation of norcocaine and benzoylecgonine after i.v. and p.o. (20-40 mg/kg) cocaine administration. Although t(1/2alpha), and t(1/2beta) were similar across the three compounds, the values of volume of distribution in the central compartment and clearance for benzoylecgonine were much smaller than those of cocaine and norcocaine. Norcocaine was not detected following i.v. cocaine; however, serum norcocaine concentrations were as high as those of oral cocaine. Both routes of cocaine administration produced benzoylecgonine. A pharmacokinetic model for the metabolite kinetics was proposed by sequentially adding the models that most adequately described the formation of each metabolite to the model of cocaine. For oral cocaine, the absolute bioavailability was 3.48%, whereas 6.04 and 2.26% of cocaine were converted to benzoylecgonine and norcocaine, respectively, during first-pass absorption regardless of dose. Furthermore, the majority of norcocaine and 92% of benzoylecgonine were formed during the first-pass absorption, leaving 8% of benzoylecgonine produced in systemic circulation. The profile of norcocaine as a metabolite confirmed the involvement of norcocaine in cocaine's behavioral effects.

  5. Effects of chronic methylphenidate on cocaine self-administration under a progressive-ratio schedule of reinforcement in rhesus monkeys.

    PubMed

    Czoty, Paul W; Martelle, Susan E; Gould, Robert W; Nader, Michael A

    2013-06-01

    It has been hypothesized that drugs that serve as substrates for dopamine (DA) and norepinephrine (NE) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters. Previous studies have shown that the DA/NE releaser d-amphetamine can decrease cocaine self-administration in preclinical and clinical studies. The present study examined the effects of methylphenidate (MPD), a DA uptake inhibitor, for its ability to decrease cocaine self-administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy. Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed-ratio 50 schedule of reinforcement; cocaine was self-administered under a progressive-ratio schedule of reinforcement in the evening. After cocaine (0.003-0.56 mg/kg per injection, i.v.) dose-response curves were determined, self-administration sessions were suspended and MPD (0.003-0.0056 mg/kg per hour, i.v.; or 1.0-9.0 mg/kg p.o., b.i.d.) was administered for several weeks. A cocaine self-administration session was conducted every 7 days. When a MPD dose was reached that either persistently decreased cocaine self-administration or produced disruptive effects, the cocaine dose-effect curve was re-determined. In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine self-administration; it took several weeks for these effects to dissipate. These data are consistent with the largely negative results of clinical trials with MPD. In contrast to the positive effects with the monoamine releaser d-amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence.

  6. Effects of chronic methylphenidate on cocaine self-administration under a progressive-ratio schedule of reinforcement in rhesus monkeys.

    PubMed

    Czoty, Paul W; Martelle, Susan E; Gould, Robert W; Nader, Michael A

    2013-06-01

    It has been hypothesized that drugs that serve as substrates for dopamine (DA) and norepinephrine (NE) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters. Previous studies have shown that the DA/NE releaser d-amphetamine can decrease cocaine self-administration in preclinical and clinical studies. The present study examined the effects of methylphenidate (MPD), a DA uptake inhibitor, for its ability to decrease cocaine self-administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy. Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed-ratio 50 schedule of reinforcement; cocaine was self-administered under a progressive-ratio schedule of reinforcement in the evening. After cocaine (0.003-0.56 mg/kg per injection, i.v.) dose-response curves were determined, self-administration sessions were suspended and MPD (0.003-0.0056 mg/kg per hour, i.v.; or 1.0-9.0 mg/kg p.o., b.i.d.) was administered for several weeks. A cocaine self-administration session was conducted every 7 days. When a MPD dose was reached that either persistently decreased cocaine self-administration or produced disruptive effects, the cocaine dose-effect curve was re-determined. In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine self-administration; it took several weeks for these effects to dissipate. These data are consistent with the largely negative results of clinical trials with MPD. In contrast to the positive effects with the monoamine releaser d-amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence. PMID:23579044

  7. Clinical Profile, Acute Care, and Middle-Term Outcomes of Cocaine-Associated ST-Segment Elevation Myocardial Infarction in an Inner-City Community.

    PubMed

    Shitole, Sanyog G; Kayo, Noel; Srinivas, Vankeepuram; Alapati, Venkatesh; Nordin, Charles; Southern, William; Christia, Panagiota; Faillace, Robert T; Scheuer, James; Kizer, Jorge R

    2016-04-15

    Although cocaine is a well-recognized risk factor for coronary disease, detailed information is lacking regarding related behavioral and clinical features of cocaine-associated ST-segment elevation myocardial infarction (STEMI), particularly in socioeconomically disadvantaged urban settings. Nor are systematic or extended follow-up data available on outcomes for cocaine-associated STEMI in the contemporary era of percutaneous coronary intervention. We leveraged a prospective STEMI registry from a large health system serving an inner-city community to characterize the clinical features, acute management, and middle-term outcomes of cocaine-related versus cocaine-unrelated STEMI. Of the 1,003 patients included, 60% were black or Hispanic. Compared with cocaine-unrelated STEMI, cocaine-related STEMI (n = 58) was associated with younger age, male gender, lower socioeconomic score, current smoking, high alcohol consumption, and human immunodeficiency virus seropositivity but less commonly with diabetes or hypertension. Cocaine users less often received drug-eluting stents or β blockers at discharge. During median follow-up of 2.7 years, rates of death, death or any rehospitalization, and death or cardiovascular rehospitalization did not differ significantly between cocaine users and nonusers but were especially high for death or any hospitalization in the 2 groups (31.4 vs 32.4 per 100 person-years, p = 0.887). Adjusted hazard ratios for outcomes were likewise not significantly different. In conclusion, in this low-income community, cocaine use occurred in a substantial fraction of STEMI cases, who were younger than their nonuser counterparts but had more prevalent high-risk habits and exhibited similarly high rates of adverse outcomes. These data suggest that programs targeting cocaine abuse and related behaviors could contribute importantly to disease prevention in disadvantaged communities. PMID:26897639

  8. Clinical Profile, Acute Care, and Middle-Term Outcomes of Cocaine-Associated ST-Segment Elevation Myocardial Infarction in an Inner-City Community.

    PubMed

    Shitole, Sanyog G; Kayo, Noel; Srinivas, Vankeepuram; Alapati, Venkatesh; Nordin, Charles; Southern, William; Christia, Panagiota; Faillace, Robert T; Scheuer, James; Kizer, Jorge R

    2016-04-15

    Although cocaine is a well-recognized risk factor for coronary disease, detailed information is lacking regarding related behavioral and clinical features of cocaine-associated ST-segment elevation myocardial infarction (STEMI), particularly in socioeconomically disadvantaged urban settings. Nor are systematic or extended follow-up data available on outcomes for cocaine-associated STEMI in the contemporary era of percutaneous coronary intervention. We leveraged a prospective STEMI registry from a large health system serving an inner-city community to characterize the clinical features, acute management, and middle-term outcomes of cocaine-related versus cocaine-unrelated STEMI. Of the 1,003 patients included, 60% were black or Hispanic. Compared with cocaine-unrelated STEMI, cocaine-related STEMI (n = 58) was associated with younger age, male gender, lower socioeconomic score, current smoking, high alcohol consumption, and human immunodeficiency virus seropositivity but less commonly with diabetes or hypertension. Cocaine users less often received drug-eluting stents or β blockers at discharge. During median follow-up of 2.7 years, rates of death, death or any rehospitalization, and death or cardiovascular rehospitalization did not differ significantly between cocaine users and nonusers but were especially high for death or any hospitalization in the 2 groups (31.4 vs 32.4 per 100 person-years, p = 0.887). Adjusted hazard ratios for outcomes were likewise not significantly different. In conclusion, in this low-income community, cocaine use occurred in a substantial fraction of STEMI cases, who were younger than their nonuser counterparts but had more prevalent high-risk habits and exhibited similarly high rates of adverse outcomes. These data suggest that programs targeting cocaine abuse and related behaviors could contribute importantly to disease prevention in disadvantaged communities.

  9. Novel triazolyl-functionalized chitosan derivatives with different chain lengths of aliphatic alcohol substituent: Design, synthesis, and antifungal activity.

    PubMed

    Li, Qing; Tan, Wenqiang; Zhang, Caili; Gu, Guodong; Guo, Zhanyong

    2015-12-11

    Chemical modification of chitosan is increasingly studied for its potential of providing new application for chitosan. Here, we modify chitosan at its primary hydroxyl via 'click chemistry', and a group of novel water soluble chitosan derivatives with substituted 1,2,3-triazolyl group were designed and synthesized. Aliphatic alcohols with different lengths were used as functional dendrons to improve the antifungal activity of chitosan derivatives. Meanwhile, their antifungal activity against two kinds of phytopathogens was estimated by hypha measurement in vitro. All the chitosan derivatives exhibited excellent activity against tested fungi. It is found that the antifungal activity of chitosan derivatives against the tested fungi increases with augment in the chain length of straight aliphatic alcohols. And the hydrophobic moiety (alkyl) at the periphery of the synthesized chitosan derivatives tends to affect their antifungal activity.

  10. The effects of prenatal cocaine exposure and gender on inhibitory control and attention.

    PubMed

    Carmody, Dennis P; Bennett, David S; Lewis, Michael

    2011-01-01

    Children exposed prenatally to cocaine show deficits in emotion regulation and inhibitory control. While controlling for the measures of medical complication in the perinatal period, environmental risk, and prenatal polydrug exposure (alcohol, tobacco, and marijuana), we examined the effects of prenatal cocaine exposure and gender on attention and inhibitory control in 203 children at ages 6, 9, and 11. Cocaine exposure affected the performance of males, but not females. Heavily exposed males showed deficits in the attention and the inhibition tasks. In addition, a significantly greater proportion of heavily exposed males (21%) than unexposed males (7%) or heavily exposed females (7%) failed to complete the task (p<0.01). Even without those poorest performing subjects, the overall accuracy for heavily exposed males (81%) was significantly reduced (p<0.05) compared to lightly exposed males (87%) and unexposed males (89%). The findings highlight the importance of considering gender specificity in cocaine exposure effects. Processes by which cocaine effects may be specific to males are discussed.

  11. Effects of prenatal cocaine/polydrug exposure on substance use by age 15

    PubMed Central

    Minnes, Sonia; Singer, Lynn; Min, Meeyoung O.; Wu, Miaoping; Lang, Adelaide; Yoon, Susan

    2014-01-01

    Objective Examined effects of prenatal cocaine exposure (PCE) on tobacco, alcohol, marijuana and cocaine use by age 15. Methods Adolescent (n = 358; 183 PCE, 175 non-prenatally cocaine exposed; NCE) drug use was assessed using urine, hair, and/or blood spot samples and self-report (Youth Risk Behavior Surveillance System; YRBSS) at ages 12 and 15. Logistic regression assessed effects of PCE on drug use controlling for other drug exposures, environment and blood lead levels (BLL). Results Adjusted percentages of drug use (PCE vs. NCE) were: tobacco 35% vs. 26% (p < .04), marijuana 33% vs. 23% (p < .04), alcohol 40% vs. 35% (p < .01), and any drugs 59% vs. 50% (p < .005). PCE adolescents were twice as likely to use tobacco (OR = 2.02, 95% CI = 1.05–3.90, p < .04), 2.2 times more likely to use alcohol (OR = 2.16, 95% CI = 1.21–3.87, p < .01) and 1.8 times more likely to use marijuana (OR = 1.81, 95% CI = 1.02–3.22, p < .04) than NCE adolescents. A race-by-cocaine-exposure interaction (p < .01) indicated PCE non-African American adolescents had greater probability of tobacco use (65%) than NCE non-African American youth (21%). PCE was associated with any drug use (OR = 2.16, CI = 1.26–3.69, p < .005), while higher BLL predicted alcohol use (p < .001). Violence exposure was a predictor of tobacco (p < .002), marijuana (p < .0007) and any drug (p < .04). Conclusions PCE and exposure to violence increased the likelihood of tobacco, marijuana or any drug use by age 15, while PCE and higher early BLL predicted alcohol use. Prevention efforts should target high risk groups prior to substance use initiation. PMID:24176200

  12. Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

    PubMed

    Hanlon, C A; Dowdle, L T; Jones, J L

    2016-01-01

    Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). PMID:27503451

  13. An Evolution of Virtual Reality Training Designs for Children with Autism and Fetal Alcohol Spectrum Disorders

    ERIC Educational Resources Information Center

    Strickland, Dorothy C.; McAllister, David; Coles, Claire D.; Osborne, Susan

    2007-01-01

    This article describes an evolution of training programs to use first-person interaction in virtual reality (VR) situations to teach safety skills to children with autism spectrum disorder (ASD) and fetal alcohol spectrum disorder (FASD). Multiple VR programs for children aged 2 to 9 were built and tested between 1992 and 2007. Based on these…

  14. The Alcohol Dehydrogenase Kinetics Laboratory: Enhanced Data Analysis and Student-Designed Mini-Projects

    ERIC Educational Resources Information Center

    Silverstein, Todd P.

    2016-01-01

    A highly instructive, wide-ranging laboratory project in which students study the effects of various parameters on the enzymatic activity of alcohol dehydrogenase has been adapted for the upper-division biochemistry and physical biochemistry laboratory. Our two main goals were to provide enhanced data analysis, featuring nonlinear regression, and…

  15. Alcohol consumption, illicit substances, and intimate partner violence in a sample of batterers in psychological treatment.

    PubMed

    Redondo Rodríguez, Natalia; Graña Gómez, José Luis

    2015-03-01

    The purpose of this study is to analyze the alcohol and illicit substance consumption characteristics in a sample of 572 batterers in treatment by court order. The results indicate that the prevalence of alcohol consumption in the past year was 89.3%, whereas within illicit substances, the prevalences were higher for cannabis (27.8%), followed by cocaine 20.3%). In order to analyze the possible effect of consumption on levels of perpetration and victimization of partner-aggression, the sample was divided into 4 groups: nonconsumers (16.3%), alcohol consumers (58.6%), illicit drug consumers (3.5%), and consumers of alcohol and illicit drugs (21.7%), finding that the groups of nonconsumers and alcohol consumers presented the lowest level of perpetration of psychological, physical, and sexual aggression and of victimization of psychological and physical aggression, whereas the group of consumers of alcohol and illicit drugs presented the highest levels. The results reveal the need to assess substance consumption when designing intervention protocols with batterers.

  16. Alcohol consumption, illicit substances, and intimate partner violence in a sample of batterers in psychological treatment.

    PubMed

    Redondo Rodríguez, Natalia; Graña Gómez, José Luis

    2015-01-01

    The purpose of this study is to analyze the alcohol and illicit substance consumption characteristics in a sample of 572 batterers in treatment by court order. The results indicate that the prevalence of alcohol consumption in the past year was 89.3%, whereas within illicit substances, the prevalences were higher for cannabis (27.8%), followed by cocaine 20.3%). In order to analyze the possible effect of consumption on levels of perpetration and victimization of partner-aggression, the sample was divided into 4 groups: nonconsumers (16.3%), alcohol consumers (58.6%), illicit drug consumers (3.5%), and consumers of alcohol and illicit drugs (21.7%), finding that the groups of nonconsumers and alcohol consumers presented the lowest level of perpetration of psychological, physical, and sexual aggression and of victimization of psychological and physical aggression, whereas the group of consumers of alcohol and illicit drugs presented the highest levels. The results reveal the need to assess substance consumption when designing intervention protocols with batterers. PMID:25879475

  17. Cocaine self-administration disrupts mesolimbic dopamine circuit function and attenuates dopaminergic responsiveness to cocaine.

    PubMed

    Siciliano, Cody A; Ferris, Mark J; Jones, Sara R

    2015-08-01

    Dopaminergic projections from the ventral midbrain to the nucleus accumbens (NAc) have long been implicated in encoding associations between reward availability and environmental stimuli. As such, this circuit is instrumental in guiding behaviors towards obtaining maximal rewards based on previous experience. Cocaine acts on the dopamine system to exert its reinforcing effects and it is thought that cocaine-induced dysregulation of dopamine neurotransmission contributes to the difficulty that cocaine addicts exhibit in selecting environmentally appropriate behaviors. Here we used cocaine self-administration combined with in vivo fast scan cyclic voltammetry in anesthetised rats to examine the function of the ventral tegmental area to NAc projection neurons. Over 5 days of cocaine self-administration (fixed-ratio 1; 1.5 mg/kg/injection; 40 injections/day), animals increased their rate of intake. Following cocaine self-administration, there was a marked reduction in ventral tegmental area-stimulated NAc dopamine release. Additionally, there was a decreased augmentation of stimulated dopamine overflow in response to a cocaine challenge. These findings demonstrate that cocaine induces a hypodopaminergic state, which may contribute to the inflexible drug-taking and drug-seeking behaviors observed in cocaine abusers. Additionally, tolerance to the ability of cocaine to elevate dopamine may lead to increased cocaine intake in order to overcome decreased effects, another hallmark of cocaine abuse. PMID:26037018

  18. Impaired insight in cocaine addiction: laboratory evidence and effects on cocaine-seeking behaviour

    SciTech Connect

    Moeller, S.J.; Moeller, S.J.; Maloney, T.; Parvaz, M.A.; Alia-Klein, N.; Woicik, P.A.; Telang, F.; Wang, G.-J.; Volkow, N.D.; Goldstein, R.Z.

    2010-04-15

    Neuropsychiatric disorders are often characterized by impaired insight into behaviour. Such an insight deficit has been suggested, but never directly tested, in drug addiction. Here we tested for the first time this impaired insight hypothesis in drug addiction, and examined its potential association with drug-seeking behaviour. We also tested potential modulation of these effects by cocaine urine status, an individual difference known to impact underlying cognitive functions and prognosis. Sixteen cocaine addicted individuals testing positive for cocaine in urine, 26 cocaine addicted individuals testing negative for cocaine in urine, and 23 healthy controls completed a probabilistic choice task that assessed objective preference for viewing four types of pictures (pleasant, unpleasant, neutral and cocaine). This choice task concluded by asking subjects to report their most selected picture type; correspondence between subjects self-reports with their objective choice behaviour provided our index of behavioural insight. Results showed that the urine positive cocaine subjects exhibited impaired insight into their own choice behaviour compared with healthy controls; this same study group also selected the most cocaine pictures (and fewest pleasant pictures) for viewing. Importantly, however, it was the urine negative cocaine subjects whose behaviour was most influenced by insight, such that impaired insight in this subgroup only was associated with higher cocaine-related choice on the task and more severe actual cocaine use. These findings suggest that interventions to enhance insight may decrease drug-seeking behaviour, especially in urine negative cocaine subjects, potentially to improve their longer-term clinical outcomes.

  19. Prospective associations between brain activation to cocaine and no-go cues and cocaine relapse*

    PubMed Central

    Prisciandaro, James J.; Myrick, Hugh; Henderson, Scott; McRae-Clark, Aimee L.; Brady, Kathleen T.

    2013-01-01

    Background The ability to predict potential for relapse to substance use following treatment could be very useful in targeting aftercare strategies. Recently, a number of investigators have focused on using neural activity measured by fMRI to predict relapse propensity. The purpose of the present study was to use fMRI to investigate prospective associations between brain reactivity to cocaine and response inhibition cues and relapse to cocaine use. Methods Thirty cocaine-dependent participants with clean cocaine urine drug screens (UDS) completed a baseline fMRI scan, including a cocaine-cue reactivity task and a go/no-go response inhibition task. After participating in a brief clinical trial of D-cycloserine for the facilitation of cocaine cue extinction, they returned for a one-week follow-up UDS. Associations between baseline activation to cocaine and inhibition cues and relapse to cocaine use were explored. Results Positive cocaine UDS was significantly associated with cocaine cue activation in the right putamen and insula, as well as bilateral occipital regions. Associations between positive cocaine UDS and activation to no-go cues were concentrated in the postcentral gyri, a region involved in response execution. Conclusions Although preliminary, these results suggest that brain imaging may be a useful tool for predicting risk for relapse in cocaine-dependent individuals. Further, larger-scale naturalistic studies are needed to corroborate and extend these findings. PMID:23683790

  20. Molecular mechanisms of cocaine reward: Combined dopamine and serotonin transporter knockouts eliminate cocaine place preference

    PubMed Central

    Sora, Ichiro; Hall, F. Scott; Andrews, Anne M.; Itokawa, Masanari; Li, Xiao-Fei; Wei, Hong-Bing; Wichems, Christine; Lesch, Klaus-Peter; Murphy, Dennis L.; Uhl, George R.

    2001-01-01

    Cocaine blocks uptake by neuronal plasma membrane transporters for dopamine (DAT), serotonin (SERT), and norepinephrine (NET). Cocaine reward/reinforcement has been linked to actions at DAT or to blockade of SERT. However, knockouts of neither DAT, SERT, or NET reduce cocaine reward/reinforcement, leaving substantial uncertainty about cocaine's molecular mechanisms for reward. Conceivably, the molecular bases of cocaine reward might display sufficient redundancy that either DAT or SERT might be able to mediate cocaine reward in the other's absence. To test this hypothesis, we examined double knockout mice with deletions of one or both copies of both the DAT and SERT genes. These mice display viability, weight gain, histologic features, neurochemical parameters, and baseline behavioral features that allow tests of cocaine influences. Mice with even a single wild-type DAT gene copy and no SERT copies retain cocaine reward/reinforcement, as measured by conditioned place-preference testing. However, mice with no DAT and either no or one SERT gene copy display no preference for places where they have previously received cocaine. The serotonin dependence of cocaine reward in DAT knockout mice is thus confirmed by the elimination of cocaine place preference in DAT/SERT double knockout mice. These results provide insights into the brain molecular targets necessary for cocaine reward in knockout mice that develop in their absence and suggest novel strategies for anticocaine medication development. PMID:11320258

  1. Individual characteristics and response to Contingency Management treatment for cocaine addiction.

    PubMed

    García-Fernández, Gloria; Secades-Villa, Roberto; García-Rodríguez, Olaya; Alvarez-López, Heli; Sánchez-Hervás, Emilio; Fernández-Hermida, José Ramón; Fernández-Artamendi, Sergio

    2011-02-01

    Voucher-based contingency management (CM) research has demonstrated efficacy for treating cocaine addiction, but few studies have examined associations between individual baseline characteristics and response to CM treatments. The aim of this study, involving 50 cocaine outpatients receiving CM for cocaine addiction, was to assess the impact of baseline characteristics on abstinence outcomes after six months of treatment. Patients who were abstinent after six months of treatment accounted for 58% of the sample. Patients with higher scores on the Alcohol area of the EuropASI and patients that were non-abstinent during the first month of treatment were less likely to achieve abstinence. These outcome predictors have implications both for treatment research and for clinical practice. Patients who do not respond early to treatment may need a more intensive intervention, and concomitant problematic alcohol use should be detected and treated. The remaining baseline variables examined were not statistically significant predictors of abstinence. This finding is important for the generalizability of CM across the range of individual characteristics of treatment-seeking cocaine abusers.

  2. Anti-cocaine antibody and butyrylcholinesterase-derived cocaine hydrolase exert cooperative effects on cocaine pharmacokinetics and cocaine-induced locomotor activity in mice

    PubMed Central

    Brimijoin, Stephen; Orson, Frank; Kosten, Tom; Kinsey, Berma; Shen, Xiao Yun; White, Sarah J.; Gao, Yang

    2012-01-01

    We are investigating treatments for cocaine abuse based on viral gene transfer of a cocaine hydrolase (CocH) derived from human butyrylcholinesterase, which can reduce cocaine-stimulated locomotion and cocaine-primed reinstatement of drug-seeking behavior in rats for many months. Here, in mice, we explored the possibility that anti-cocaine antibodies can complement the actions of CocH to reduce cocaine uptake in brain and block centrally-evoked locomotor stimulation. Direct injections of test proteins showed that CocH (0.3 or 1 mg/kg) was effective by itself in reducing drug levels in plasma and brain of mice given cocaine (10 mg/kg, s.c., or 20 mg/kg, i.p). Administration of cocaine antibody per se at a low dose (8 mg/kg, i.p.) exerted little effect on cocaine distribution. However, a higher dose of antibody (12 mg/kg) caused peripheral trapping (increased plasma drug levels), which led to increased cocaine metabolism by CocH, as evidenced by a 6-fold rise in plasma benzoic acid. Behavioral tests with small doses of CocH and antibody (1 and 8 mg/kg, respectively) showed that neither agent alone reduced mouse locomotor activity triggered by a very large cocaine dose (100 mg/kg, i.p.). However, dual treatment completely suppressed the locomotor stimulation. Altogether, we found cooperative and possibly synergistic actions that warrant further exploration of dual therapies for treatment of cocaine abuse. PMID:22960160

  3. Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties

    PubMed Central

    McMurray, Matthew S.; Oguz, Ipek; Rumple, Ashley M.; Paniagua, Beatriz; Styner, Martin A.; Johns, Josephine M.

    2014-01-01

    Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance data must be carefully collected using translational methods. The goal of this study was two-fold: 1) determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging; and 2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1–20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus palladus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures, but does not result

  4. Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties.

    PubMed

    McMurray, Matthew S; Oguz, Ipek; Rumple, Ashley M; Paniagua, Beatriz; Styner, Martin A; Johns, Josephine M

    2015-01-01

    Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance, data must be carefully collected using translational methods. The goal of this study was two-fold: (1) to determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging, and (2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1-20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus pallidus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures but does not

  5. Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties.

    PubMed

    McMurray, Matthew S; Oguz, Ipek; Rumple, Ashley M; Paniagua, Beatriz; Styner, Martin A; Johns, Josephine M

    2015-01-01

    Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance, data must be carefully collected using translational methods. The goal of this study was two-fold: (1) to determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging, and (2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1-20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus pallidus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures but does not

  6. Nucleus accumbens shell and core involvement in drug context-induced reinstatement of cocaine seeking in rats

    PubMed Central

    Fuchs, Rita A.; Ramirez, Donna R.; Bell, Guinevere H.

    2008-01-01

    Rationale The nucleus accumbens (NAC) is a functionally heterogeneous brain region with respect to its involvement in cocaine-seeking behavior triggered by drug-associated explicit conditioned stimuli, foot shock stress, or cocaine itself in the reinstatement animal model of drug relapse. However, it is not known whether the NAC or its subregions are critical for reinstatement of cocaine-seeking behavior produced by re-exposure to a previously cocaine-paired environmental context. Objectives The present study was designed to evaluate potentially unique contributions of the NAC core and shell to this behavior. Materials and methods Rats were trained to lever press for unsignaled cocaine infusions (0.15 mg/infusion, intravenous) in a distinct environmental context. Lever responding was then extinguished in a distinctly different environmental context (extinction context) during a minimum of seven daily training sessions. Subsequently, using a counterbalanced testing design, rats were re-exposed to the cocaine-paired context or the extinction context while cocaine seeking (i.e., responding on the previously cocaine-reinforced lever) was assessed. Before each test session, neural activity was inhibited selectively in the NAC core or shell using bilateral microinfusions of the γ-aminobutyric acid agonists, baclofen and muscimol (0/0 or 1.0/0.1 mM; 0.3 μl per hemisphere). Results Neural inactivation of the NAC shell or core attenuated responding in the cocaine context and, interestingly, increased responding in the extinction context. Control experiments indicated no effects on general activity or food-reinforced instrumental behavior. Conclusions These findings suggest that both subregions of the NAC may promote context-induced reinstatement by facilitating drug context-induced motivation for cocaine and context discrimination. PMID:18597075

  7. [Comorbidity between cocaine addiction and personality disorders].

    PubMed

    Fernández-Montalvo, J; Lorea, I

    2007-01-01

    The aim of this paper was to review the current knowledge about the comorbidity between cocaine dependence and personality disorders. Results concerning a specific profile of cocaine patients are not conclusive. The prevalence rate of personality disorders in cocaine dependents is very heterogeneous (with a mean of 66% of cases), and a great variability is observed between all the studies carried out. There is a tendency for a higher proportion of cocaine dependents to be found within the cluster B category (mainly antisocial and borderline). Lastly, implications of this kind of study for future research and clinical practice are commented upon.

  8. [Comorbidity between cocaine addiction and personality disorders].

    PubMed

    Fernández-Montalvo, J; Lorea, I

    2007-01-01

    The aim of this paper was to review the current knowledge about the comorbidity between cocaine dependence and personality disorders. Results concerning a specific profile of cocaine patients are not conclusive. The prevalence rate of personality disorders in cocaine dependents is very heterogeneous (with a mean of 66% of cases), and a great variability is observed between all the studies carried out. There is a tendency for a higher proportion of cocaine dependents to be found within the cluster B category (mainly antisocial and borderline). Lastly, implications of this kind of study for future research and clinical practice are commented upon. PMID:17898818

  9. Molecular approaches to treatments for cocaine abuse

    NASA Astrophysics Data System (ADS)

    Flippen-Anderson, Judith L.; George, Clifford; Deschamps, Jeffrey R.

    2003-02-01

    Cocaine is a potent stimulant of the central nervous system with severe addiction potential. Its abuse is a major problem worldwide. The exact mechanism of action of cocaine is still uncertain but it is known that its reinforcing and stimulant effects are related to its ability to inhibit the membrane bound dopamine transporter (DAT). This paper discusses efforts that are underway to identify ligands for possible use in the treatment of cocaine abuse. Much of this effort has been focussed on understanding cocaine interactions at DAT receptor sites.

  10. [Cocaine addiction: current data for the clinician].

    PubMed

    Karila, Laurent; Zarmdini, Rim; Petit, Aymeric; Lafaye, Geneviève; Lowenstein, William; Reynaud, Michel

    2014-01-01

    Cocaine remains the second most commonly used illicit drug worldwide after cannabis. Observed levels of cocaine use among countries considerably vary. An increased cocaine use is recorded in the general European population. Cocaine addiction is a worldwide public health problem, which has somatic, psychiatric, socio-economic and judicial complications. It is a multifactorial disorder variable in its clinical manifestations and heritable. Compared to the general population, there is a high prevalence of somatic and psychiatric disorders among cocaine-dependent patients. There are predictable dose-related effects of pharmacological action of cocaine and effects which are uncommon, unrelated to dose and occur randomly in this population. The number of patients entering drug treatment for primary cocaine use has been increasing in Europe for several years. However, there is no specific pharmacotherapy with established efficacy for the treatment of cocaine addiction, nor is any medication approved by regulatory authorities for such treatment. Recent controlled clinical studies and laboratory studies have highlighted some very promising medications. The perfect therapeutic platform for abstinence initiation and relapse prevention of cocaine addiction is a combination of pharmacological treatments and behavioral treatments. Targeting somatic and psychiatric comorbidity is another way to use pharmacological treatments in addictions. PMID:23727012

  11. Neuropsychiatric effects of cocaine use disorders.

    PubMed Central

    Nnadi, Charles U.; Mimiko, Olubansile A.; McCurtis, Henry L.; Cadet, Jean Lud

    2005-01-01

    Individuals who use cocaine report a variety of neuropsychiatric symptoms that are yet to be adequately targeted with treatment modalities. To address this problem requires an understanding of these symptoms and their neurobiological origins. Our paper reviewed the existing data on the neuropsychiatic implications of cocaine. We conducted a Medline search from 1984-2004 using terms, such as "cocaine", "cocaine addiction", "cocaine abuse", "cocaine neuropsychiatry" and "dual diagnosis". The search produced additional reference materials that were used in this review, although we focused on data that have likely clinical implications. The literature evidence suggested that, whereas acute cocaine overdose is potentially fatal, the ingestion of mild-to-moderate doses could result in fatal or nonfatal neuropsychiatric events. Also, chronic cocaine use may be associated with deficits in neurocognition, brain perfusion and brain activation patterns. Some of these deficits were unresolved with periods of abstinence ranging from 3-200 days. Taken together, these studies suggest the need for further investigations to fully characterize the neurobiological substrates of cocaine use disorders (CUDs) with the future possibility of more efficient treatment modalities. PMID:16334497

  12. Sleep Regulates Incubation of Cocaine Craving.

    PubMed

    Chen, Bo; Wang, Yao; Liu, Xiaodong; Liu, Zheng; Dong, Yan; Huang, Yanhua H

    2015-09-30

    After withdrawal from cocaine, chronic cocaine users often experience persistent reduction in total sleep time, which is accompanied by increased sleep fragmentation resembling chronic insomnia. This and other sleep abnormalities have long been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here, we report that after prolonged withdrawal from cocaine self-administration, rats exhibited persistent reduction in nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep, as well as increased sleep fragmentation. In an attempt to improve sleep after cocaine withdrawal, we applied chronic sleep restriction to the rats during their active (dark) phase of the day, which selectively decreased the fragmentation of REM sleep during their inactive (light) phase without changing NREM or the total amount of daily sleep. Animals with improved REM sleep exhibited decreased incubation of cocaine craving, a phenomenon depicting the progressive intensification of cocaine seeking after withdrawal. In contrast, experimentally increasing sleep fragmentation after cocaine self-administration expedited the development of incubation of cocaine craving. Incubation of cocaine craving is partially mediated by progressive accumulation of calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). After withdrawal from cocaine, animals with improved REM sleep exhibited reduced accumulation of CP-AMPARs in the NAc, whereas increasing sleep fragmentation accelerated NAc CP-AMPAR accumulation. These results reveal a potential molecular substrate that can be engaged by sleep to regulate cocaine craving and relapse, and demonstrate sleep-based therapeutic opportunities for cocaine addiction. Significance statement: Sleep abnormalities are common symptoms in chronic drug users long after drug withdrawal. These withdrawal-associated sleep symptoms, particularly reduction in total sleep time and deteriorating sleep quality, have been

  13. Cocaine, a risk factor for myocardial infarction.

    PubMed

    Galasko, G I

    1997-06-01

    Cocaine usage goes back thousands of years, to the times of the Incas. Over the past 20 years, its use has increased dramatically, especially in America, and adverse cardiovascular reactions to the drug have begun to be reported. The first report of myocardial infarction temporally related to the recreational use of cocaine appeared in 1982. Since then, myocardial infarction has become recognized as the drug's most common cardiovascular consequence, with over 250 cases now documented in the literature. This review discusses the history of cocaine use, its pharmacology, the possible pathological mechanisms underlying the pathogenesis of myocardial ischaemia and infarction, and current ideas on the management of cocaine-induced myocardial infarction.

  14. Study design to develop and pilot-test a web intervention for partners of military service members with alcohol misuse

    PubMed Central

    2014-01-01

    Background Alcohol misuse among military service members from the recent conflicts in Iraq and Afghanistan is over two times higher compared to misuse in the civilian population. Unfortunately, in addition to experiencing personal consequences from alcohol misuse, partners and family members of alcohol-misusing service members also suffer in negative ways from their loved one’s drinking. These family members represent important catalysts for helping their loved ones identify problem drinking and overcoming the barriers to seeking care. This paper describes the protocol to a pilot study evaluating a 4-session, web-based intervention (WBI) for concerned partners (CPs) of service members with alcohol misuse. Methods/design The WBI will be adapted from the Community Reinforcement and Family Training (CRAFT) intervention. In the first phase, we will develop and beta-test the WBI with 15–20 CPs. In the second phase, we will randomize CPs to WBI (n = 50) or to delayed-WBI (n = 50) and evaluate the impact of the WBI on CPs’ perceptions of service member help-seeking and drinking, as well as the CP’s well-being and relationship satisfaction 3 months after the intervention. In the third phase, we will recruit 15–20 service members whose partners have completed the study. We will interview the service members to learn how the CP-focused WBI affected them and to assess whether they would be receptive to a follow-on WBI module to help them. Discussion This project has the potential to benefit a large population of military service members who may be disproportionately affected by recent conflicts and whose drinking misuse would otherwise go undetected and untreated. It also develops a new prevention model that does not rely on service members or partners attending a hospital or clinical facility to access care. Trial registration NCT02073825. PMID:25179672

  15. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  16. Real-time assessment of alcohol drinking and drug use in opioid-dependent polydrug users.

    PubMed

    Preston, Kenzie L; Jobes, Michelle L; Phillips, Karran A; Epstein, David H

    2016-10-01

    We investigated relationships between drinking, other drug use, and drug craving, using ecological momentary assessment (EMA), in a sample of polydrug users who were not heavy drinkers. In a prospective longitudinal cohort study, 114 heroin and cocaine users on methadone-maintenance treatment carried handheld electronic diaries during waking hours and were screened for drug and alcohol use for up to 25 weeks. Individuals who fulfilled the Diagnostic and Statistical Manual of Mental Disorders criteria for alcohol abuse or dependence were excluded. Participants responded to 2-5 random prompts per day to report on their moods, cravings, and activities and initiated entries when they used or acutely craved heroin or cocaine. Drinking alcohol was assessed in both types of entries. Breath alcohol was measured three times weekly. Participants reported drinking alcohol in 1.6% of random-prompt entries, 3.7% of event-contingent entries when craving cocaine and/or heroin, and 11.6% of event-contingent entries when using cocaine and/or heroin. Alcohol drinking was also associated with higher craving ratings and prestudy alcohol use. More drinking was detected by ambulatory self-report than by in-clinic breath testing. Even though we had screened out heavy drinkers from our sample of polydrug users, drinking was associated with heroin and cocaine craving and actual use. PMID:27579810

  17. [Cocaine-related gastric perforation].

    PubMed

    Ring, A; Stein, E; Stern, J

    2010-06-01

    Since the 1980s the abuse of cocaine has been -associated with gastroduodenal perforations in the United States. Here, we report the case of a 28-year-old man who came to our hospital with severe abdominal pain after smoking cocaine. Physical examination revealed generalised abdominal guarding. His X-ray did not show any free intraperitoneal air. However, there was a slightly elevated white blood cell count. Upon laparoscopic exploration of the abdomen, the -patient was found to have a generalised peritonitis secondary to a perforation of the prepyloric anterior wall. The operative procedure consisted of ulcer excision and primary closure with a pyloroplasty as well as an extensive abdominal irrigation after laparotomy.

  18. Translating the Semi-Structured Assessment for Drug Dependence and Alcoholism in the Western Pacific: Rationale, Study Design and Reliability of Alcohol Dependence

    PubMed Central

    Quinn, Amity E.; Rosen, Rochelle K.; McGeary, John E.; Amoa, Francine; Kranzler, Henry R.; Francazio, Sarah; McGarvey, Stephen T.; Swift, Robert M.

    2014-01-01

    Aims: The aims of this study were to develop a bilingual version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) in English and Samoan and determine the reliability of assessments of alcohol dependence in American Samoa. Methods: The study consisted of development and reliability-testing phases. In the development phase, the SSADDA alcohol module was translated and the translation was evaluated through cognitive interviews. In the reliability-testing phase, the bilingual SSADDA was administered to 40 ethnic Samoans, including a sub-sample of 26 individuals who were retested. Results: Cognitive interviews indicated the initial translation was culturally and linguistically appropriate except items pertaining to alcohol tolerance, which were modified to reflect Samoan concepts. SSADDA reliability testing indicated diagnoses of DSM-III-R and DSM-IV alcohol dependence were reliable. Reliability varied by language of administration. Conclusion: The English/Samoan version of the SSADDA is appropriate for the diagnosis of DSM-III-R alcohol dependence, which may be useful in advancing research and public health efforts to address alcohol problems in American Samoa and the Western Pacific. The translation methods may inform researchers translating diagnostic and assessment tools into different languages and cultures. PMID:24936588

  19. Lethal toxicity from equimolar infusions of cocaine and cocaine metabolites in conscious and anesthetized rats.

    PubMed

    Mets, B; Virag, L

    1995-11-01

    We compared the lethal toxicity of cocaine with that of three of its metabolites to determine the contribution of these metabolites to the lethal potential from cocaine infusion. Equimolar quantities of cocaine, norcocaine, benzoylecgonine, and ecgonine methyl ester were infused in conscious rats to determine onset of convulsions and respiratory arrest. In addition, the convulsive and respiratory toxicity for cocaine and norcocaine were evaluated in anesthetized rats and their circulatory toxicity in anesthetized and ventilated rats. Norcocaine infusion resulted in earlier onset of convulsions and respiratory arrest in conscious rats than cocaine and earlier onset of circulatory arrest. Plasma concentrations of norcocaine and cocaine were not different at these times. Benzoylecgonine and ecgonine methyl ester were less potent convulsants and respiratory depressants than norcocaine and cocaine, with ecgonine methyl ester more respiratory depressant than benzoylecgonine. Pentobarbital anesthesia enhanced the respiratory depression and suppressed or delayed the onset of convulsions from norcocaine and cocaine infusion. Prolonged infusion of cocaine to circulatory arrest resulted in benzoylecgonine concentrations approximately 60%, and norcocaine concentrations approximately 5%, of the cocaine concentration, but no detectable ecgonine methyl ester formation. We conclude that although norcocaine, ecgonine methyl ester, and benzoylecgonine administered separately have lethal potential in massive dosages, death from cocaine overdose primarily results from the parent compound and not from metabolite formation.

  20. A thermostable bacterial cocaine esterase rapidly eliminates cocaine from brain in nonhuman primates

    PubMed Central

    Howell, L L; Nye, J A; Stehouwer, J S; Voll, R J; Mun, J; Narasimhan, D; Nichols, J; Sunahara, R; Goodman, M M; Carroll, F I; Woods, J H

    2014-01-01

    A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a KM of 1.33+0.085 μM. In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the first to evaluate the effects of CocE on cocaine brain levels. Positron emission tomogrpahy neuroimaging of [11C]cocaine was used to evaluate the time course of cocaine elimination from brain in the presence and absence of CocE in nonhuman primates. Systemic administration of CocE eliminated cocaine from the rhesus-monkey brain approximately three times faster than control conditions via peripheral actions through attenuating the input function from blood plasma. The efficiency of this process is sufficient to alleviate or prevent adverse central nervous system effects induced by cocaine. Although the present study used tracer doses of cocaine to access brain clearance, these findings further support the development of CocE for the treatment of acute cocaine toxicity. PMID:24984194

  1. Electroencephalographic activity and mood in cocaine-dependent outpatients: effects of cocaine cue exposure.

    PubMed

    Bauer, L O; Kranzler, H R

    1994-08-01

    Electroencephalographic (EEG) and subjective reactions to cocaine cues were evaluated in 18 cocaine-dependent outpatients, after 14 or fewer days of abstinence, and 16 noncocaine-dependent controls. EEG activity and desire for cocaine were recorded while subjects viewed three 5-min films that featured either cocaine-associated, erotic, or neutral stimuli. Other measures of mood state and cocaine craving, derived from the Mood Adjective Checklist and the Cocaine Craving Questionnaire, respectively, were recorded immediately after each film. Analyses of absolute EEG power within six frequency bands (delta, theta, slow and fast alpha, slow and fast beta) revealed no EEG abnormalities in the cocaine-dependent group under any condition. In both subject groups, the cocaine-associated and erotic films produced a similar reduction in total EEG power. The cocaine-associated and erotic films also produced a similar increase in the self-rated desire for cocaine, but this change only occurred in the cocaine-dependent group. PMID:7948456

  2. A thermostable bacterial cocaine esterase rapidly eliminates cocaine from brain in nonhuman primates.

    PubMed

    Howell, L L; Nye, J A; Stehouwer, J S; Voll, R J; Mun, J; Narasimhan, D; Nichols, J; Sunahara, R; Goodman, M M; Carroll, F I; Woods, J H

    2014-01-01

    A long-acting, thermostable bacterial cocaine esterase (CocE) has been identified that rapidly degrades cocaine with a K(M) of 1.33+0.085 μM. In vivo evaluation of CocE has shown protection against convulsant and lethal effects of cocaine in rodents, confirming the therapeutic potential of CocE against cocaine overdose. However, the current study is the first to evaluate the effects of CocE on cocaine brain levels. Positron emission tomogrpahy neuroimaging of [(11)C]cocaine was used to evaluate the time course of cocaine elimination from brain in the presence and absence of CocE in nonhuman primates. Systemic administration of CocE eliminated cocaine from the rhesus-monkey brain approximately three times faster than control conditions via peripheral actions through attenuating the input function from blood plasma. The efficiency of this process is sufficient to alleviate or prevent adverse central nervous system effects induced by cocaine. Although the present study used tracer doses of cocaine to access brain clearance, these findings further support the development of CocE for the treatment of acute cocaine toxicity. PMID:24984194

  3. Statistics-enhanced multistage process models for integrated design &manufacturing of poly (vinyl alcohol) treated buckypaper

    NASA Astrophysics Data System (ADS)

    Wang, Kan

    Carbon nanotube (CNT) is considered a promising engineering material because of its exceptional mechanical, electrical, and thermal properties. Buckypaper (BP), a thin sheet of assembled CNTs, is an effective way to handle CNTs in macro scale. Pristine BP is a fragile material which is held together by weak van der Waals attractions among CNTs. This dissertation introduces a modified filtration based manufacturing process which uses poly (vinyl alcohol) (PVA) to treat BP. This treatment greatly improves the handleability of BP, reduces the spoilage during transferring, and shortens the production time. The multistage manufacturing process of PVA-treated BP is discussed in this dissertation, and process models are developed to predict the nanostructure of final products from the process parameters. Based on the nanostructure, a finite element based physical model for prediction of Young's modulus is also developed. This accuracy of this physical model is further improved by statistical methods. The aim of this study is to investigate and improve the scalability of the manufacturing process of PVA-treated BP. To achieve this goal, various statistical tools are employed. The unique issues in nanomanufacturing also motivate the development of new statistical tools and modification of existing tools. Those issues include the uncertainties in nanostructure characterization due to the scale, limited number experimental data due to high cost of raw materials, large variation in final product due to the random nature in structure, and the high complexity in physical models due to the small scale of structural building blocks. This dissertation addresses those issues by combining engineering field knowledge and statistical methods. The resulting statistics-enhanced physical model provides an approach to design the manufacturing process of PVA-treated BP for a targeting property and tailor the robustness of the final product by manipulating the process parameters. In addition

  4. Manipulating a "cocaine engram" in mice.

    PubMed

    Hsiang, Hwa-Lin Liz; Epp, Jonathan R; van den Oever, Michel C; Yan, Chen; Rashid, Asim J; Insel, Nathan; Ye, Li; Niibori, Yosuke; Deisseroth, Karl; Frankland, Paul W; Josselyn, Sheena A

    2014-10-15

    Experience with drugs of abuse (such as cocaine) produces powerful, long-lasting memories that may be important in the development and persistence of drug addiction. The neural mechanisms that mediate how and where these cocaine memories are encoded, consolidated and stored are unknown. Here we used conditioned place preference in mice to examine the precise neural circuits that support the memory of a cocaine-cue association (the "cocaine memory trace" or "cocaine engram"). We found that a small population of neurons (∼10%) in the lateral nucleus of amygdala (LA) were recruited at the time of cocaine-conditioning to become part of this cocaine engram. Neurons with increased levels of the transcription factor CREB were preferentially recruited or allocated to the cocaine engram. Ablating or silencing neurons overexpressing CREB (but not a similar number of random LA neurons) before testing disrupted the expression of a previously acquired cocaine memory, suggesting that neurons overexpressing CREB become a critical hub in what is likely a larger cocaine memory engram. Consistent with theories that coordinated postencoding reactivation of neurons within an engram or cell assembly is crucial for memory consolidation (Marr, 1971; Buzsáki, 1989; Wilson and McNaughton, 1994; McClelland et al., 1995; Girardeau et al., 2009; Dupret et al., 2010; Carr et al., 2011), we also found that post-training suppression, or nondiscriminate activation, of CREB overexpressing neurons impaired consolidation of the cocaine memory. These findings reveal mechanisms underlying how and where drug memories are encoded and stored in the brain and may also inform the development of treatments for drug addiction.

  5. Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

    PubMed Central

    Schindler, Charles W; Goldberg, Steven R

    2012-01-01

    One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID:22300096

  6. Urge-specific and lifestyle coping strategies of cocaine abusers: relationships to treatment outcomes.

    PubMed

    Rohsenow, Damaris J; Martin, Rosemarie A; Monti, Peter M

    2005-05-01

    This study investigated specific coping techniques for effectiveness in reducing cocaine use after treatment. The urge-specific strategies questionnaire-cocaine (USS-C) assessed frequency of use of 21 strategies for coping with urges. The general change strategies questionnaire-cocaine (GCS-C) assessed frequency of use of 21 lifestyle change strategies designed to maintain abstinence. Cocaine-dependent patients were assessed at follow-up after residential treatment for USS-C (n=59 at 3 months, 84 at 6 months), GCS-C (n=89 at 3 months, 120 at 6 months) and substance use. Less cocaine use was associated with urge coping by thinking about negative or positive consequences, alternative behaviors, distraction, relaxation/meditation, escape, offer refusal, spiritual methods, behavior chains, mastery messages, problem-solving, meeting or sponsor, or seeking social support. The lifestyle change strategies of thinking about consequences, working toward goals, thinking of oneself as sober, clean recreation, regular relaxation, avoiding temptations, not carrying much money, living with clean people, seeking social support, spiritual involvement, keeping busy, and health activities were also associated with less cocaine use. Results suggest focusing coping skills training on these potentially effective strategies.

  7. Social stress increases the acquisition of cocaine self-administration in male and female rats.

    PubMed

    Haney, M; Maccari, S; Le Moal, M; Simon, H; Piazza, P V

    1995-11-01

    The effect of social stress on the vulnerability to commence cocaine self-administration was examined in Sprague-Dawley rats repeatedly exposed to aggressive attack by a same-sex opponent. Both sexes were studied, since the factors influencing the acquisition of drug self-administration in females have not been defined. Male and female rats encountered an aggressive male or lactating female opponent on four separate occasions over the course of one week. Control male and female rats were not exposed to attack. All animals were implanted with jugular catheters, and six days later placed into the self-administration box, where a nose-poke in the designated 'active hole' resulted in a 20 microliters injection of cocaine (0.32 mg/kg). Nose-pokes in an 'inactive' hole had no effect. Male and female rats that had experienced social stress self-administered more cocaine than non-defeated controls. The difference between the stressed and non-stressed animals in the number of cocaine injections was not present during the first few days of exposure to cocaine, but became more pronounced over time. Social stress increased the number of responses for cocaine, but did not alter the number of non-specific responses. Sex differences in self-administration were not significant. Therefore, social status appears to be a potent influence in the onset of drug taking behavior in both male and female rats. PMID:8581502

  8. Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine.

    PubMed

    Featherstone, Robert E; Burton, Christie L; Coppa-Hopman, Romina; Rizos, Zoë; Sinyard, Judy; Kapur, Shitij; Fletcher, Paul J

    2009-10-01

    Schizophrenia is associated with increased rates of substance abuse that are thought to be the result of changes in cortical and mesolimbic dopamine activity. Previous work has shown that gestational methylazoxymethanol acetate (MAM) treatment induces increased mesolimbic dopamine activity when given around the time of embryonic day 17 (ED17), suggesting that MAM treatment may model some aspects of schizophrenia. Given that increased dopaminergic activity facilitates aspects of drug self-administration and reinstatement of drug seeking, the current experiments sought to assess cocaine self-administration in MAM treated animals. Experiment 1 examined the acquisition of cocaine self-administration in ED17 MAM and saline treated rats using a sub-threshold dose of cocaine. In experiment 2 ED17 MAM and saline treated animals were trained to self-administer cocaine and were then assessed under varying doses of cocaine (dose-response), followed by extinction and drug-induced reinstatement of responding. A subset of these animals was trained on a win-shift radial maze task, designed to detect impairments in hippocampal-dependent memory. In experiment 3, MAM and saline treated animals were assessed on a progressive ratio schedule of cocaine delivery. Finally, in experiment 4 MAM and saline treated animals were assessed on cocaine-induced locomotor activity across a range of doses of cocaine. MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed.

  9. Cocaine alters dendritic spine density in cortical and subcortical brain regions of the postpartum and virgin female rat

    PubMed Central

    Frankfurt, Maya; Salas-Ramirez, Kaliris; Friedman, Eitan; Luine, Victoria

    2011-01-01

    Cocaine use during pregnancy induces profound neural and behavioral deficits in both mother and offspring. The present study was designed to compare the effects of cocaine exposure on spine density of postpartum and virgin female rat brains. Timed, pregnant, primiparous rats were injected with either cocaine (30 mg/kg) or saline, once daily, from gestational day 8–20. Twenty four hours after giving birth, dam brains were processed for Golgi-impregnation. Since cocaine effects in female rats have not been determined, virgin females were also injected with the same dose of cocaine or saline for 12 days and sacrificed 24h after the last injection for comparison. Pregnant rats had significantly greater spine density in the medial amygdala (MeA) and medial preoptic area (MPOA) and lower spine density in CA1 than virgin females independent of cocaine treatment. Cocaine significantly increased dendritic spine density on the apical branch of pyramidal cells in the prefrontal cortex (PFC, 15%), both apical (13%) and basal (14.8%) branches of CA1 and cells in the MeA (28%) of pregnant rats. In the MPOA, cocaine administration resulted in a decrease in dendritic spine density (14%) in pregnant rats. In virgin females, cocaine had fewer effects but did increase dendritic spine density on both branches of CA1 neurons and in the MeA. The present study is the first to demonstrate that spine density differs between pregnant and virgin females and that pregnancy makes the brain more vulnerable to cocaine, which has important clinical implications. PMID:21480383

  10. Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

    PubMed

    Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

    2016-06-01

    This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. PMID:27001454

  11. Cocaine use among heroin users in Spain: the diffusion of crack and cocaine smoking. Spanish Group for the Study on the Route of Administration of Drugs

    PubMed Central

    Barrio, G.; De la Fuente, L.; Royuela, L.; Diaz, A.; Rodriguez-Artalej..., F.

    1998-01-01

    STUDY OBJECTIVE: To describe the prevalence and patterns of use of crack and cocaine hydrochloride among heroin users in Spain. To explore if the expansion of heroin smoking is accompanied by a similar phenomenon for cocaine. DESIGN: Cross sectional study in 1995. Face to face interviews using a structured questionnaire. SETTING: Three cities with different prevalences of heroin use by smoking: high (Seville), intermediate (Madrid), and low (Barcelona). PARTICIPANTS: 909 heroin users, 452 in treatment and 457 out of treatment. MAIN RESULTS: Last month prevalence of crack use was 62.3% in Seville, 19.4% in Madrid, and 7.7% in Barcelona. Most users in Madrid (86.5%) and Barcelona (100%) generally prepared their own crack, usually with ammonia as alkali; in Seville most users (69.7%) bought preprocessed crack. The proportion of users who began taking cocaine (crack or cocaine hydrochloride) by smoking has increased progressively since the seventies, rising to 74.1% in Seville, 61.5% in Madrid, and 28% in Barcelona in 1992-1995, with the earliest increase in Seville. The factors associated with crack use were: residence in Seville (odds ratio (OR) = 16.3), cocaine hydrochloride use mainly by smoking (OR = 5.0), by sniffing (OR = 2.7) or by injecting (OR = 2.5), heroin use mainly by smoking (OR = 2.8) and weekly use of cannabis (OR = 1.9). CONCLUSIONS: In Spain smoking cocaine may be progressively diffusing from the south west to the north east, similar to what has happened with smoking heroin, but beginning later in time. The factors associated with smoking cocaine are basically ecological or cultural in nature (characteristics of the available drugs and the main route of heroin administration in each city).   PMID:9616422

  12. Maternal Cocaine Addiction: Correlates and Consequences.

    ERIC Educational Resources Information Center

    Hawley, Theresa Lawton

    This study investigated the effects of cocaine addiction on mothers' ability to care for their children. The population interviewed included 25 cocaine-addicted mothers in a drug treatment center and a comparison group of 25 mothers of children in a Head Start program. Each mother was questioned about: (1) her pregnancy with a specific child…

  13. Children of Cocaine: Facing the Issues.

    ERIC Educational Resources Information Center

    Fact Find, 1990

    1990-01-01

    Statistical data illustrate the incidence of babies who have been prenatally exposed to cocaine. The damaging effects of maternal cocaine use on the fetus, infant, and young child are described, including: (1) prenatal strokes, malformed kidneys and limbs, and deformed hearts and lungs; (2) physical problems, social and emotional problems, and…

  14. Opiate and Cocaine Exposed Newborns: Growth Outcomes.

    ERIC Educational Resources Information Center

    Butz, Arlene M.; Kaufmann, Walter E.; Royall, Richard; Kolodner, Ken; Pulsifer, Margaret B.; Lears, Mary Kathleen; Henderson, Robin; Belcher, Harolyn; Sellers, Sherri; Wilson, Modena

    1999-01-01

    Examines growth parameters at birth in 204 infants born to mothers who used cocaine and/or opiates during pregnancy. Outcome measures included birth weight, length, and head circumference. Study provides support that in utero cocaine exposure may confer more risk for somatic growth retardation at birth than opiate exposure. (Author/GCP)

  15. [Sucrose reward promotes rats' motivation for cocaine].

    PubMed

    Li, Yan-Qing; LE, Qiu-Min; Yu, Xiang-Chen; Ma, Lan; Wang, Fei-Fei

    2016-06-25

    Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine. PMID:27350195

  16. Children of Cocaine: Treatment and Child Care.

    ERIC Educational Resources Information Center

    Howze, Kate; Howze, Wendell M.

    Information concerning the treatment and care of children addicted to cocaine is provided. Contents: (1) describe the drug; (2) put cocaine use in its historical and demographic perspectives; (3) report findings of a study documenting the incidence of maternal substance abuse in Pinellas County, Florida; (4) point out false perceptions,…

  17. Supported metal catalysts for alcohol/sugar alcohol steam reforming

    SciTech Connect

    Davidson, Stephen; Zhang, He; Sun, Junming; Wang, Yong

    2014-08-21

    Despite extensive studies on hydrogen production via steam reforming of alcohols and sugar alcohols, catalysts typically suffer a variety of issues from poor hydrogen selectivity to rapid deactivation. Here, we summarize recent advances in fundamental understanding of functionality and structure of catalysts for alcohol/sugar alcohol steam reforming, and provide perspectives on further development required to design highly efficient steam reforming catalysts.

  18. Post-training cocaine administration facilitates habit learning and requires the infralimbic cortex and dorsolateral striatum.

    PubMed

    Schmitzer-Torbert, Neil; Apostolidis, Steven; Amoa, Romeo; O'Rear, Connor; Kaster, Michael; Stowers, Josh; Ritz, Robert

    2015-02-01

    Human drug addiction is a complex disorder, in which exogenous substances are able to recruit and maintain behaviors involved in drug taking. Many drugs that are addictive in humans are able to act on natural brain systems for learning and memory, and while many memory systems may be affected by addictive drugs, work with operant tasks has shown that addictive drugs (e.g. cocaine and alcohol) are particularly effective in recruiting habit learning systems, compared to natural rewards. It is currently unknown if the ability of addictive drugs to facilitate habit learning depends on a direct action on habit learning systems in the brain, versus the rewarding properties of drug administration. To differentiate between these options, rats were trained to perform two actions (lever pressing), each of which was rewarded with a different natural reward. After acquiring the behavior, rats received three training sessions which were followed by post-training injections of saline or cocaine (5 or 10mg/kg, i.p.). Using sensory-specific satiety, extinction tests revealed that lever pressing for actions which were paired with saline were sensitive to devaluation (typical of goal-directed behaviors) while actions which were paired with cocaine were not sensitive to devaluation (typical of habitual behaviors). Lesions of the infralimbic or dorsolateral striatum were able to block the action of post-training cocaine injections. These data indicate that, within individual rats, cocaine injections facilitate the transition of behavior to habitual control for actions that have been recently performed, without a general facilitation of habit learning, and that this action of cocaine requires brain areas that are critical for learning natural habits.

  19. The Nociceptin Receptor as an Emerging Molecular Target for Cocaine Addiction.

    PubMed

    Lutfy, Kabirullah; Zaveri, Nurulain T

    2016-01-01

    Cocaine addiction is a global public health and socioeconomic issue that requires pharmacological and cognitive therapies. Currently there are no FDA-approved medications to treat cocaine addiction. However, in preclinical studies, interventions ranging from herbal medicine to deep-brain stimulation have shown promise for the therapy of cocaine addiction. Recent developments in molecular biology, pharmacology, and medicinal chemistry have enabled scientists to identify novel molecular targets along the pathways involved in drug addiction. In 1994, a receptor that showed a great deal of homology to the traditional opioid receptors was characterized. However, endogenous and exogenous opioids failed to bind to this receptor, which led scientists to name it opioid receptor-like receptor, now referred to as the nociceptin receptor. The endogenous ligand of NOPr was identified a year later and named orphanin FQ/nociceptin. Nociceptin and NOPr are widely distributed throughout the CNS and are involved in many physiological responses, such as food intake, nociceptive processing, neurotransmitter release, etc. Furthermore, exogenous nociceptin has been shown to regulate the activity of mesolimbic dopaminergic neurons, glutamate, and opioid systems, and the stress circuit. Importantly, exogenous nociceptin has been shown to reduce the rewarding and addictive actions of a number of drugs of abuse, such as psychostimulants, alcohol, and opioids. This paper reviews the existing literature on the role of endogenous nociceptin in the rewarding and addictive actions of cocaine. The effect of exogenous nociceptin on these processes is also reviewed. Furthermore, the effects of novel small-molecule NOPr ligands on these actions of cocaine are discussed. Overall, a review of the literature suggests that NOPr could be an emerging target for cocaine addiction pharmacotherapy. PMID:26810001

  20. Post-training cocaine administration facilitates habit learning and requires the infralimbic cortex and dorsolateral striatum.

    PubMed

    Schmitzer-Torbert, Neil; Apostolidis, Steven; Amoa, Romeo; O'Rear, Connor; Kaster, Michael; Stowers, Josh; Ritz, Robert

    2015-02-01

    Human drug addiction is a complex disorder, in which exogenous substances are able to recruit and maintain behaviors involved in drug taking. Many drugs that are addictive in humans are able to act on natural brain systems for learning and memory, and while many memory systems may be affected by addictive drugs, work with operant tasks has shown that addictive drugs (e.g. cocaine and alcohol) are particularly effective in recruiting habit learning systems, compared to natural rewards. It is currently unknown if the ability of addictive drugs to facilitate habit learning depends on a direct action on habit learning systems in the brain, versus the rewarding properties of drug administration. To differentiate between these options, rats were trained to perform two actions (lever pressing), each of which was rewarded with a different natural reward. After acquiring the behavior, rats received three training sessions which were followed by post-training injections of saline or cocaine (5 or 10mg/kg, i.p.). Using sensory-specific satiety, extinction tests revealed that lever pressing for actions which were paired with saline were sensitive to devaluation (typical of goal-directed behaviors) while actions which were paired with cocaine were not sensitive to devaluation (typical of habitual behaviors). Lesions of the infralimbic or dorsolateral striatum were able to block the action of post-training cocaine injections. These data indicate that, within individual rats, cocaine injections facilitate the transition of behavior to habitual control for actions that have been recently performed, without a general facilitation of habit learning, and that this action of cocaine requires brain areas that are critical for learning natural habits. PMID:25460040

  1. Post-training cocaine administration facilitates habit learning and requires the infralimbic cortex and dorsolateral striatum

    PubMed Central

    Schmitzer-Torbert, Neil; Apostolidis, Steven; Amoa, Romeo; O’Rear, Connor; Kaster, Michael; Stowers, Josh; Ritz, Robert

    2014-01-01

    Human drug addiction is a complex disorder, in which exogenous substances are able to recruit and maintain behaviors involved in drug taking. Many drugs that are addictive in humans are able to act on natural brain systems for learning and memory, and while many memory systems may be affected by addictive drugs, work with operant tasks has shown that addictive drugs (e.g. cocaine and alcohol) are particularly effective in recruiting habit learning systems, compared to natural rewards. It is currently unknown if the ability of addictive drugs to facilitate habit learning depends on a direct action on habit learning systems in the brain, versus the rewarding properties of drug administration. To differentiate between these options, rats were trained to perform two actions (lever pressing), each of which was rewarded with a different natural reward. After acquiring the behavior, rats received three training sessions which were followed by post-training injections of saline or cocaine (5 or 10 mg/kg, i.p.). Using sensory-specific satiety, extinction tests revealed that lever pressing for actions which were paired with saline were sensitive to devaluation (typical of goal-directed behaviors) while actions which were paired with cocaine were not sensitive to devaluation (typical of habitual behaviors). Lesions of the infralimbic or dorsolateral striatum were able to block the action of post-training cocaine injections. These data indicate that, within individual rats, cocaine injections facilitate the transition of behavior to habitual control for actions that have been recently performed, without a general facilitation of habit learning, and that this action of cocaine requires brain areas that are critical for learning natural habits. PMID:25460040

  2. Nasal toxicity of cocaine: a hypercoagulable effect?

    PubMed Central

    Patel, R.; Shah, R.; Baredes, S.; Spillert, C. R.; Lazaro, E. J.

    2000-01-01

    Nasal insufflation of cocaine injures the nasal mucosa and can perforate the septum. Cocaine-induced vasoconstriction resulting in ischemia is one of the methods that may be responsible for this damage. We are determining whether cocaine also produces a hypercoagulable state that may compound factors which have been previously established to cause damage to the nasal mucosa and septum. This study uses Modified Recalcification Time (MRT), a test developed in our laboratory that has the ability to measure the overall coagulation process. Our study revealed no connection between cocaine and enhanced platelet function or monocyte-released tissue factor. The coagulation process was unaffected by the addition of the drug, so we conclude that cocaine does not cause a hypercoagulable state and cannot assist in the explanation regarding the ischemic changes of the nasal septum. PMID:10800286

  3. Cocaine seeking by rats is a goal-directed action.

    PubMed

    Olmstead, M C; Lafond, M V; Everitt, B J; Dickinson, A

    2001-04-01

    In two experiments rats were trained to self-administer intravenous cocaine on chained schedules using different responses in the initial (drug-seeking) and terminal (drug-taking) links. In both between- (Experiment 1) and within-subject designs (Experiment 2), the drug-taking response was then either extinguished or reinforced in the absence of the opportunity to perform the seeking response. In a subsequent extinction test with the seeking manipulanda alone, the rate of drug seeking was reduced after the prior extinction of the associated taking response. An additional group trained with a sucrose reinforcer showed a comparable devaluation effect. These findings demonstrate that seeking responses for cocaine and food rewards are mediated by a representation of the contingency between seeking responses and the opportunity to take the reward.

  4. Alcohol Alert

    MedlinePlus

    ... Us You are here Home » Alcohol Alert Alcohol Alert The NIAAA Alcohol Alert is a quarterly bulletin that disseminates important research ... text. To order single copies of select Alcohol Alerts, see ordering Information . To view publications in PDF ...

  5. Alcoholism - resources

    MedlinePlus

    Resources - alcoholism ... The following organizations are good resources for information on alcoholism : Alcoholics Anonymous -- www.aa.org Al-Anon/Alateen -- www.al-anon.org/home National Institute on Alcohol ...

  6. Alcoholic neuropathy

    MedlinePlus

    Neuropathy - alcoholic; Alcoholic polyneuropathy ... The exact cause of alcoholic neuropathy is unknown. It likely includes both a direct poisoning of the nerve by the alcohol and the effect of poor nutrition ...

  7. Alcohol Facts

    MedlinePlus

    ... raquo Alcohol Facts Alcohol Facts Listen Drinks like beer, malt liquor, wine, and hard liquor contain alcohol. Alcohol is the ingredient that gets you drunk. Hard liquor—such as whiskey, rum, or gin—has more ...

  8. Behaviors, Attitudes and Knowledge of UNO Students Regarding Drugs, Alcohol and Tobacco: 1989.

    ERIC Educational Resources Information Center

    Hunnicutt, David; Davis, Joe

    1989-01-01

    This report describes alcohol, tobacco, and other drug use among 715 University of Nebraska at Omaha (UNO) students. The report focuses on drug use at the higher frequency levels, rather than reporting proportions who have ever used various drugs. The separate classes of drugs distinguished are alcohol, tobacco, cocaine, marijuana, and…

  9. Alcohol Alert: Genetics of Alcoholism

    MedlinePlus

    ... and Reports » Alcohol Alert » Alcohol Alert Number 84 Alcohol Alert Number 84 Print Version The Genetics of ... immune defense system. Genes Encoding Enzymes Involved in Alcohol Breakdown Some of the first genes linked to ...

  10. Sensitization enhances acquisition of cocaine self-administration in female rats: Estradiol further enhances cocaine intake after acquisition

    PubMed Central

    Zhao, Wei; Becker, Jill B.

    2011-01-01

    Cocaine self-administration in rodents has been used widely as a preclinical model of cocaine use in humans. In laboratory animals, estradiol enhances behavioral sensitization to cocaine and the acquisition of cocaine self-administration in female rats. The rewarding effect of cocaine has been shown to be enhanced following behavioral sensitization in male rats. This experiment examined whether behavioral sensitization to cocaine would promote cocaine-taking behavior in female rats, and whether estradiol could further modulate cocaine-taking behavior in cocaine-sensitized rats. Ovariectomized female rats were pretreated with either cocaine or saline for 4 days per week for 3 weeks. Self-administration sessions started 2 weeks after the last dose of drug. Female Sprague–Dawley rats received either estradiol or oil 30 min prior to the start of each session and self-administration was carried out 5 days per week for 4 weeks. The dose of cocaine self-administered each week was as follows (in mg/kg/infusion): week 1, 0.1; week 2, 0.1; week 3, 0.15; and week 4, 0.4. The rats that received cocaine pretreatment took fewer days to acquire cocaine self-administration and took more cocaine than rats that received saline pretreatment. Estradiol enhanced cocaine intake during the last six self-administration sessions after acquisition but did not affect acquisition of self-administration at the lowest doses of cocaine used. In conclusion, cocaine sensitization promotes the acquisition of cocaine self-administration in female rats. Furthermore, prior cocaine experience is more powerful than estradiol at enhancing acquisition, while estradiol enhances intake of cocaine after acquisition of self-administration. PMID:19769978

  11. Cocaine metabolism: cocaine and norcocaine hydrolysis by liver and serum esterases.

    PubMed

    Stewart, D J; Inaba, T; Lucassen, M; Kalow, W

    1979-04-01

    The hydrolysis of cocaine and its N-demethylated product, norcocaine, by esterases was examined in liver and serum. Both liver and serum enzymatically formed ecgonine methyl ester from cocaine. The liver enzyme had a much lower affinity for cocaine than that of serum, indicating that a different form of esterase was present in liver. The liver enzyme had a similar affinity for both norcocaine and cocaine. Likewise, the serum enzyme showed similar affinities for both substrates. The Vmax estimates, however, were consistently higher for norcocaine than cocaine in both liver and serum. Benzoyl ecgonine, a major metabolite of cocaine formed by hydrolysis, was not produced enzymatically in either serum or liver; the rate of spontaneous formation at physiological pH suggests that this metabolite may arise nonenzymatically in the body.

  12. Design of a Web-based individual coping and alcohol-intervention program (web-ICAIP) for children of parents with alcohol problems: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background It has been estimated that approximately 20% of all Swedish children grow up with parents having alcohol problems, which may result in negative outcomes among these children. Therefore, most Swedish municipalities provide resources for support, but at the same time figures reveal that not even 2% receive support, mainly due to difficulties in identifying and recruiting these children into support programs. Delivering intervention programs to children and adolescents via the Internet seems a promising strategy, but to date, the number of web-based interventions aimed at this target group is very scarce. We have therefore developed a novel internet-delivered therapist assisted self-management intervention called the web-ICAIP (Individual Coping and Alcohol Intervention Program) for adolescents having parents with alcohol problems. The purpose of the program is to strengthen adolescents' coping behavior, improve their mental health, and postponing the onset or decreasing risky alcohol consumption. This paper describes the web-ICAIP and the design of a randomized controlled trial (RCT) to measure the efficacy of this intervention. Methods/Design The RCT will include at least 183 adolescents (15-19 year old) who will be randomly allocated to two conditions where one group has access to the web-ICAIP and the other is a waiting list control group. Participants will be recruited from websites containing information and facts for adolescents about alcohol and other drugs. Possible participants will be screened using the short version of the Children of Alcoholics Screening Test (CAST-6). The assessment consists of a baseline and two follow-up measurements taking place after two and six months, respectively. The primary outcomes include the Center for Epidemiological Studies Depression Scale (CES-DC), a coping behavior scale, and also the short version of the Alcohol Use Disorders Identification Test (AUDIT-C). Additional outcomes include the "Ladder of life

  13. Hormones, nicotine, and cocaine: clinical studies.

    PubMed

    Mello, Nancy K

    2010-06-01

    Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (2 min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine's sustained positive effects (<20 min), ratings of "high" and "rush" began to decrease within one or two puffs of a high-nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse and the implications for treatment of these addictive disorders are discussed.

  14. [Ten years of emergency attendances for cocaine-users in Spain].

    PubMed

    Galicia, Miguel; Nogué, Santiago; Burillo-Putze, Guillermo

    2014-10-01

    Cocaine is the second most consumed illegal drug in the western world, following cannabis. Since 1998, it is also the drug that more attendances generate in different emergency devices, and it is responsible for more of 60% of the emergencies directly related to drug consumption. This work reviews the main Spanish scientific articles published in the last 10 years, in which different factors related to the use of this drug have been analyzed in relation to the use of emergency by cocaine users. A total of 8,795 patients were included (interval 57-1,755), with an average age of 32.64 years (SD 3.02), and an average percentage of positives to cocaine of 54.78% (SD 47.03); there were 7 works with 100% of subjects being positive to cocaine. Males predominated with an average of 78.69% (SD 12). They presented cardiovascular symptoms in 30% cases (SD 22.7), neurological symptoms in 11.6% cases (SD 4.28) and psychiatric symptoms in 49.32% cases (SD 23.87). There was a multiple consumption in 49.02% of patients (interval 4.3-76.2), fundamentally associated with alcohol (57.78%, SD 6.18) and cannabis (21.56%, SD 10.72). Two hundred and forty-six patients (2.8%) needed admission and 8 died (0.09%). PMID:24461737

  15. [Ten years of emergency attendances for cocaine-users in Spain].

    PubMed

    Galicia, Miguel; Nogué, Santiago; Burillo-Putze, Guillermo

    2014-10-01

    Cocaine is the second most consumed illegal drug in the western world, following cannabis. Since 1998, it is also the drug that more attendances generate in different emergency devices, and it is responsible for more of 60% of the emergencies directly related to drug consumption. This work reviews the main Spanish scientific articles published in the last 10 years, in which different factors related to the use of this drug have been analyzed in relation to the use of emergency by cocaine users. A total of 8,795 patients were included (interval 57-1,755), with an average age of 32.64 years (SD 3.02), and an average percentage of positives to cocaine of 54.78% (SD 47.03); there were 7 works with 100% of subjects being positive to cocaine. Males predominated with an average of 78.69% (SD 12). They presented cardiovascular symptoms in 30% cases (SD 22.7), neurological symptoms in 11.6% cases (SD 4.28) and psychiatric symptoms in 49.32% cases (SD 23.87). There was a multiple consumption in 49.02% of patients (interval 4.3-76.2), fundamentally associated with alcohol (57.78%, SD 6.18) and cannabis (21.56%, SD 10.72). Two hundred and forty-six patients (2.8%) needed admission and 8 died (0.09%).

  16. Reactivity and Regulation of Motor Responses in Cocaine-Exposed Infants

    PubMed Central

    Fallone, Melissa Duncan; LaGasse, Linda L.; Lester, Barry M.; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.

    2014-01-01

    Effects of prenatal exposure to cocaine on the reactivity and regulation of the motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants and 487 non-exposed comparison infants were coded by examiners masked to exposure status. Exposure status was determined by meconium assay and maternal self-report of prenatal cocaine use. Infants were presented with a series of 17 visual, auditory and tactile stimuli for 30-second each. Intensity and latency of limb movement responses on a subset of items were analyzed to test the following hypotheses: CE infants are more active in general; CE infants exhibit increased movement levels for a larger proportion of time in response to stimulation; the motor systems of CE infants are more reactive to stimulation (e.g., shorter latencies to respond); and CE infants are poorer regulators of the motor system. Results CE infants were not more active in general and data do not indicate a more highly reactive motor system. However, CE infants exhibited increased movement levels for a larger proportion of time in response to stimulation. Additional analysis of movement exhibited during three tactile items found increased movement lability in CE infants and different patterns of responding, suggesting that the effects of prenatal cocaine exposure on the motor system may vary by context. Covariate effects for tobacco, alcohol, and marijuana are also reported. PMID:24583252

  17. Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration.

    PubMed

    Ellefsen, Kayla N; Concheiro, Marta; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2016-03-01

    Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze(®) (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed Cmax median (range) concentrations were 932 (394-1574)μg/L for cocaine and 248 (96.9-953)μg/L for BE. SS observed cocaine and BE Cmax median (range) concentrations trended lower at 732 (83.3-1892)μg/L and 360 (77.2-836)μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID:26851651

  18. The cerebellum on cocaine: plasticity and metaplasticity.

    PubMed

    Vazquez-Sanroman, Dolores; Leto, Ketty; Cerezo-Garcia, Miguel; Carbo-Gas, María; Sanchis-Segura, Carla; Carulli, Daniela; Rossi, Ferdinando; Miquel, Marta

    2015-09-01

    Despite the fact that several data have supported the involvement of the cerebellum in the functional alterations observed after prolonged cocaine use, this brain structure has been traditionally ignored and excluded from the circuitry affected by addictive drugs. In the present study, we investigated the effects of a chronic cocaine treatment on molecular and structural plasticity in the cerebellum, including BDNF, D3 dopamine receptors, ΔFosB, the Glu2 AMPA receptor subunit, structural modifications in Purkinje neurons and, finally, the evaluation of perineuronal nets (PNNs) in the projection neurons of the medial nucleus, the output of the cerebellar vermis. In the current experimental conditions in which repeated cocaine treatment was followed by a 1-week withdrawal period and a new cocaine challenge, our results showed that cocaine induced a large increase in cerebellar proBDNF levels and its expression in Purkinje neurons, with the mature BDNF expression remaining unchanged. Together with this, cocaine-treated mice exhibited a substantial enhancement of D3 receptor levels. Both ΔFosB and AMPA receptor Glu2 subunit expressions were enhanced in cocaine-treated animals. Significant pruning in Purkinje dendrite arborization and reduction in the size and density of Purkinje boutons contacting deep cerebellar projection neurons accompanied cocaine-dependent increase in proBDNF. Cocaine-associated effects point to the inhibitory Purkinje function impairment, as was evidenced by lower activity in these cells. Moreover, the probability of any remodelling in Purkinje synapses appears to be decreased due to an upregulation of extracellular matrix components in the PNNs surrounding the medial nuclear neurons.

  19. Cocaine attenuates vasoconstriction to ethanol

    SciTech Connect

    Bove, A.A.; Morley, D.; Vosacek, R.; Zhang, X.Y.; Shah, R. )

    1991-03-11

    The purpose of this study was to determine the combined effects of cocaine and ethanol on vasomotor tone. Using a standard isolated vascular ring preparation, 24 rings from 7 New Zealand White Rabbits were studied. All rings were denuded as verified by methacholine challenge. The dose response to NE for each ring was used as a standard for vasoconstrictors Dose response curves to ETH and C were done in random order. Concentrations of both ETH and C employed were physiologically attainable in man and below thresholds for coma or death. The dose response curve to ETH was repeated after addition of 4 {times} 10{sup {minus}5} M C to the arterial bath. After adding 1,500 ug/ml of ETH, the dose response curve to C was repeated. Ethanol, alone caused significant vasoconstriction of arterial rings. After the addition of C to the bath, the dose response to ETH was significantly shifted to the right, peak contraction achieved was 36.6 {plus minus} 3.2% of maximal NE contraction. Cocaine alone did not result in any change in resting tension of the rings. When ETH was added to the bath, C caused vasoconstriction, the peak value equivalent to 12.5 {plus minus} 2.2% of maximal contraction to NE.

  20. Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.

    PubMed

    Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J; Oliveira, Catarina R; Santos, Maria S

    2013-06-01

    Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue. PMID:23542814

  1. Detection of cocaine, norcocaine, and cocaethylene in the meconium of premature neonates.

    PubMed

    Browne, S; Moore, C; Negrusz, A; Tebbett, I; Covert, R; Dusick, A

    1994-11-01

    Our objective was to investigate the methodologic detection of cocaine abuse during pregnancy by determining the viability of meconium analysis for cocaine and its metabolites using chromatographic procedures as an alternative to urine testing using enzyme multiplied immunoassay technique. Our design was as follows: meconium and urine were taken from 106 very low birthweight premature babies. Meconium analysis for cocaine and its metabolites using extraction and chromatographic analysis was compared with the criterion standard immunoassay testing for urine. The work was carried out at The University of Chicago Hospital, Department of Pediatrics and the University of Illinois at Chicago, Department of Pharmacodynamics. Our patients were very low birthweight, premature babies (mean birthweight 1109 g; mean gestational age 29.1 weeks). Gender was evenly divided between male and female. The outcome measures were as follows: two active metabolites, norcocaine and cocaethylene, were detected in the meconium, but not in the urine, of some of the neonates. Determination of cocaine exposure in the newborn influenced assignment of babies in research studies as well as psychosocial evaluation and subsequent treatment of the neonate. Our results were: of the 106 meconium samples analyzed, 21 (19.8%) were positive for cocaine (n = 19, 0.24-0.78 mg/kg), norcocaine (n = 7, 0.10-0.56 mg/kg), cocaethylene (n = 1, 0.12 mg/kg) or combinations thereof. Benzoylecgonine was not detected in any of the samples. Of the urine samples analyzed by immunoassay, only 8 (7.5%) were positive for cocaine metabolites. We conclude that meconium is a better sample than urine for determining cocaine exposure in utero.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine.

    PubMed

    Hueza, Isis M; Ponce, Fernando; Garcia, Raphael C T; Marcourakis, Tânia; Yonamine, Maurício; Mantovani, Cínthia de C; Kirsten, Thiago B

    2016-01-01

    The use of smoked illicit drugs has spread dramatically, but few studies use proper devices to expose animals to inhalational abused drugs despite the availability of numerous smoking devices that mimic tobacco exposure in rodents. Therefore, the present study developed an inexpensive device to easily expose laboratory animals to smoked drugs. We used crack cocaine as the drug of abuse, and the cocaine plasma levels and the behaviors of animals intoxicated with the crack cocaine were evaluated to prove inhaled drug absorption and systemic activity. We developed an acrylic device with two chambers that were interconnected and separated by a hatch. Three doses of crack (100, 250, or 500 mg), which contained 63.7% cocaine, were burned in a pipe, and the rats were exposed to the smoke for 5 or 10 min (n=5/amount/period). Exposure to the 250-mg dose for 10 min achieved cocaine plasma levels that were similar to those of users (170 ng/mL). Behavioral evaluations were also performed to validate the methodology. Rats (n=10/group) for these evaluations were exposed to 250 mg of crack cocaine or air for 10 min, twice daily, for 28 consecutive days. Open-field evaluations were performed at three different periods throughout the experimental design. Exposed animals exhibited transient anorexia, increased motor activity, and shorter stays in central areas of the open field, which suggests reduced anxiety. Therefore, the developed model effectively exposed animals to crack cocaine, and this model may be useful for the investigation of other inhalational abused drugs.

  3. A new exposure model to evaluate smoked illicit drugs in rodents: A study of crack cocaine.

    PubMed

    Hueza, Isis M; Ponce, Fernando; Garcia, Raphael C T; Marcourakis, Tânia; Yonamine, Maurício; Mantovani, Cínthia de C; Kirsten, Thiago B

    2016-01-01

    The use of smoked illicit drugs has spread dramatically, but few studies use proper devices to expose animals to inhalational abused drugs despite the availability of numerous smoking devices that mimic tobacco exposure in rodents. Therefore, the present study developed an inexpensive device to easily expose laboratory animals to smoked drugs. We used crack cocaine as the drug of abuse, and the cocaine plasma levels and the behaviors of animals intoxicated with the crack cocaine were evaluated to prove inhaled drug absorption and systemic activity. We developed an acrylic device with two chambers that were interconnected and separated by a hatch. Three doses of crack (100, 250, or 500 mg), which contained 63.7% cocaine, were burned in a pipe, and the rats were exposed to the smoke for 5 or 10 min (n=5/amount/period). Exposure to the 250-mg dose for 10 min achieved cocaine plasma levels that were similar to those of users (170 ng/mL). Behavioral evaluations were also performed to validate the methodology. Rats (n=10/group) for these evaluations were exposed to 250 mg of crack cocaine or air for 10 min, twice daily, for 28 consecutive days. Open-field evaluations were performed at three different periods throughout the experimental design. Exposed animals exhibited transient anorexia, increased motor activity, and shorter stays in central areas of the open field, which suggests reduced anxiety. Therefore, the developed model effectively exposed animals to crack cocaine, and this model may be useful for the investigation of other inhalational abused drugs. PMID:26391341

  4. Sex differences in the conditioned rewarding effects of cocaine.

    PubMed

    Russo, Scott J; Jenab, Shirzad; Fabian, Sosimo J; Festa, Eugene D; Kemen, Lynne M; Quinones-Jenab, Vanya

    2003-04-25

    Several recent reports have demonstrated sex differences in the behavioral and neurochemical response to cocaine. However, it is not clear whether differences exist in cocaine reward or the extent to which adrenal hormones regulate cocaine-induced conditioned place preference (CPP) in either sex. To address these questions, side-by-side comparisons were conducted to determine the effects of conditioning length, cocaine dose and adrenalectomy on cocaine CPP in male and female rats. Female rats demonstrated cocaine CPP after four pairing sessions, while male rats required eight pairing sessions to develop CPP for cocaine. Also, female rats developed CPP at cocaine doses of 5 and 10 mg/kg while male rats required higher cocaine doses (20 mg/kg). Overall, females had higher blood serum levels of corticosterone. Furthermore, a dose-dependent effect on serum levels of corticosterone was observed only in female rats, where rats conditioned with 20 mg/kg cocaine had significantly higher serum levels of corticosterone than rats conditioned with 5 mg/kg cocaine. However, adrenalectomy did not affect CPP for cocaine in either sex. These results suggest that a female's higher sensitivity to cocaine's rewarding effects is not completely mediated by the hypothalamic-pituitary-adrenal axis. Therefore, sex differences in the acquisition and/or expression of cocaine CPP may be regulated by other mechanisms, such as the hypothalamic-pituitary-gonadal axis.

  5. Severity of Prenatal Cocaine Exposure and Child Language Functioning Through Age Seven Years: A Longitudinal Latent Growth Curve Analysis

    PubMed Central

    Bandstra, Emmalee S.; Vogel, April L.; Morrow, Connie E.; Xue, Lihua; Anthony, James C.

    2009-01-01

    The current study estimates the longitudinal effects of severity of prenatal cocaine exposure on language functioning in an urban sample of full-term African-American children (200 cocaine-exposed, 176 noncocaine-exposed) through age 7 years. The Miami Prenatal Cocaine Study sample was enrolled prospectively at birth, with documentation of prenatal drug exposure status through maternal interview and toxicology assays of maternal and infant urine and infant meconium. Language functioning was measured at ages 3 and 5 years using the Clinical Evaluation of Language Fundamentals–Preschool (CELF-P) and at age 7 years using the Core Language Domain of the NEPSY: A Developmental Neuropsychological Assessment. Longitudinal latent growth curve analyses were used to examine two components of language functioning, a more stable aptitude for language performance and a time-varying trajectory of language development, across the three time points and their relationship to varying levels of prenatal cocaine exposure. Severity of prenatal cocaine exposure was characterized using a latent construct combining maternal self-report of cocaine use during pregnancy by trimesters and maternal and infant bioassays, allowing all available information to be taken into account. The association between severity of exposure and language functioning was examined within a model including factors for fetal growth, gestational age, and IQ as intercorrelated response variables and child’s age, gender, and prenatal alcohol, tobacco, and marijuana exposure as covariates. Results indicated that greater severity of prenatal cocaine exposure was associated with greater deficits within the more stable aptitude for language performance (D = −0.071, 95% CI = −0.133, −0.009; p = 0.026). There was no relationship between severity of prenatal cocaine exposure and the time-varying trajectory of language development. The observed cocaine-associated deficit was independent of multiple alternative

  6. From Ancient Chinese Medicine to a Novel Approach to Treat Cocaine Addiction.

    PubMed

    Diamond, Ivan; Yao, Lina

    2015-01-01

    Pharmacologic agents for CNS disorders are often inhibitors that occupy receptors, with frequent unavoidable side effects likely due to continuous binding. This review summarizes development of a novel aldehyde dehydrogenase 2 (ALDH2) inhibitor that specifically targets unique drug related episodic surges in dopamine (DA), a pathophysiologic mechanism that appears to underlie much of drug-seeking behavior. We have synthesized highly selective novel ALDH2 inhibitors (ALDH2i) that block alcohol- and cocaine cue-induced surges in nucleus accumbens (NAc) DA and prevent reinstatement of alcohol heavy drinking, cocaine self-administration and reinstatement of cocaine relapse-like behavior. The mechanism of action of ALDH2i depends on inhibiting dopamine aldehyde (DOPAL) clearance by ALDH2, enabling unmetabolized DOPAL to condense with DA to generate tetrahydropapaveroline (THP). THP selectively inhibits the activated (phosphorylated) tyrosine hydroxylase (TH) to suppress DA synthesis. Selective inhibition of ALDH2 appears to have therapeutic potential for treating cue-induced drug relapse, a major unmet need for treating addicted subjects. PMID:26022266

  7. Prefrontal cortical volume reduction associated with frontal cortex function deficit in 6-week abstinent crack-cocaine dependent men

    PubMed Central

    Fein, George; Di Sclafani, Victoria; Meyerhoff, Dieter J.

    2010-01-01

    Background This study examined regional cortical volumes in 6-week abstinent men dependent on crack-cocaine only (Cr) or on both crack-cocaine and alcohol (CrA). Our goal was to test the a priori hypothesis of prefrontal cortical volume reduction, along with associated impairments in frontal mediated functions, and to look for differences between the Cr and CrA groups. Methods Structural magnetic resonance imaging (MRI) of the brain and neuropsychological assessment were performed on 17 6-week abstinent Cr subjects, 29 six-week abstinent CrA subjects, and 20 normal controls. Cortical volume was quantified in the prefrontal, parietal, temporal and occipital regions. Results Cr and CrA subjects showed comparable reductions in prefrontal gray matter volume compared to controls; this reduction was negatively associated with performance impairments in the executive function domain. Conclusions Dependence on Cr (with or without concomitant alcohol dependence) was associated with reduced prefrontal cortical volume. Cr dependence with concomitant alcohol dependence was not associated with greater prefrontal volume reductions than Cr dependence alone. The existence of these findings at 6-week abstinence indicates that they are not a result of acute cocaine or alcohol exposure. The association of reduced prefrontal cortical volume with cognitive impairments in frontal cortex mediated abilities suggests that this reduced cerebral volume has functional consequences. PMID:12167554

  8. The impact of minimum legal drinking age laws on alcohol consumption, smoking, and marijuana use: evidence from a regression discontinuity design using exact date of birth.

    PubMed

    Yörük, Barış K; Yörük, Ceren Ertan

    2011-07-01

    This paper uses a regression discontinuity design to estimate the impact of the minimum legal drinking age laws on alcohol consumption, smoking, and marijuana use among young adults. Using data from the National Longitudinal Survey of Youth (1997 Cohort), we find that granting legal access to alcohol at age 21 leads to an increase in several measures of alcohol consumption, including an up to a 13 percentage point increase in the probability of drinking. Furthermore, this effect is robust under several different parametric and non-parametric models. We also find some evidence that the discrete jump in alcohol consumption at age 21 has negative spillover effects on marijuana use but does not affect the smoking habits of young adults. Our results indicate that although the change in alcohol consumption habits of young adults following their 21st birthday is less severe than previously known, policies that are designed to reduce drinking among young adults may have desirable impacts and can create public health benefits.

  9. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Alcoholic content. 4.36... Alcoholic content. (a) Alcoholic content shall be stated in the case of wines containing more than 14..., either the type designation “table” wine (“light” wine) or the alcoholic content shall be stated....

  10. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Alcoholic content. 4.36... Alcoholic content. (a) Alcoholic content shall be stated in the case of wines containing more than 14..., either the type designation “table” wine (“light” wine) or the alcoholic content shall be stated....

  11. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alcoholic content. 4.36... Alcoholic content. (a) Alcoholic content shall be stated in the case of wines containing more than 14..., either the type designation “table” wine (“light” wine) or the alcoholic content shall be stated....

  12. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Alcoholic content. 4.36... Alcoholic content. (a) Alcoholic content shall be stated in the case of wines containing more than 14..., either the type designation “table” wine (“light” wine) or the alcoholic content shall be stated....

  13. 27 CFR 4.36 - Alcoholic content.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Alcoholic content. 4.36... Alcoholic content. (a) Alcoholic content shall be stated in the case of wines containing more than 14... alcohol content may be stated, but need not be stated if the type designation “table” wine (or...

  14. Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study

    PubMed Central

    Xu, Lin; Jiang, Chao Qiang; Cheng, Kar Keung; Au Yeung, Shiu Lun Ryan; Zhang, Wei Sen; Lam, Tai Hing; Schooling, Catherine Mary

    2015-01-01

    Background Observational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people. Methods An instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of ≥10 indicates the IV is not weak. Results In men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F-statistic was 7 precluding IV analysis. Conclusion In Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations. PMID:26356841

  15. Levamisole-contaminated cocaine: a hairy affair.

    PubMed

    van der Veer, Tjeerd; Pennings, Ed; Tervaert, J W Cohen; Korswagen, Lindy-Anne

    2015-01-01

    Levamisole-contaminated cocaine can induce severe systemic vasculitis. The diagnosis can be challenging, especially when substance abuse is uncertain. We present the case of a 42-year-old woman suffering from vasculitis due to levamisole-contaminated cocaine, who persistently denied substance abuse. Symptoms included ulcerating skin lesions, arthralgia and myalgia, and the occurrence of an ileal intussusception. The definitive diagnosis was made using hair testing for toxins. She recovered through cocaine abstinence, but re-exposure resulted in a severe relapse with glomerulonephritis. Importantly, at time of the relapse, the patient became positive for both myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA) and proteinase 3-ANCA. Cocaine-levamisole-induced vasculitis poses a great clinical challenge. The proper diagnostic strategy and therapy is still controversial. We highlight our diagnostic and therapeutic considerations, including hair testing for definitive proof of exposure. PMID:26311010

  16. Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men.

    PubMed

    Goletiani, Nathalie V; Mendelson, Jack H; Sholar, Michelle B; Siegel, Arthur J; Mello, Nancy K

    2009-02-01

    Nalbuphine, a mixed micro-/kappa-opioid analgesic, may have potential as a new medication for the treatment of cocaine abuse. Kappa-opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and both kappa-selective and mixed micro-/kappa-opioids reduce cocaine self-administration by rhesus monkeys. Because cocaine's interactions with the hypothalamic-pituitary-adrenal and (HPA) hypothalamic-pituitary-gonadal (HPG) axes may contribute to its reinforcing properties, we examined the effects of cocaine alone and in combination with nalbuphine. Neuroendocrine effects of a single dose of cocaine alone (0.2 mg/kg, IV), with nalbuphine (5 mg/70 kg, IV)+cocaine (0.2 mg/kg, IV) in combination were compared in seven adult men (ages 18-35) who met DSM-IV criteria for current cocaine abuse. Cocaine alone, and in combination with nalbuphine was administered on separate test days under placebo-controlled, double blind conditions. Cocaine stimulated ACTH, cortisol, and LH, whereas cocaine+nalbuphine in combination produced a smaller increase in ACTH, and decreased cortisol and LH. Thus it appears that nalbuphine attenuated cocaine's effects on ACTH, cortisol, and LH. These data are consistent with our earlier report that nalbuphine modestly attenuated cocaine's positive subjective effects, and that the subjective and cardiovascular effects of cocaine+nalbuphine in combination were not additive. PMID:18848957

  17. Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions.

    PubMed

    Pudiak, Cindy M; KuoLee, Rhonda; Bozarth, Michael A

    2014-07-01

    This study examined tolerance to cocaine's threshold-lowering effect in brain stimulation reward (BSR) following continuous cocaine infusions and secondly, used the nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) to determine NO's involvement in the development of cocaine tolerance. Animals were continuously infused with saline or cocaine (30 mg/kg per day) via osmotic minipump for 14 days and injected daily with saline or L-NAME (30 mg/kg, i.p.) following BSR testing. Saline-treated animals continuously infused with saline showed stable BSR thresholds across the 14-day infusion period. Saline-treated animals continuously infused with cocaine showed markedly lowered BSR thresholds on Day 1 followed by a progressive increase in BSR thresholds across the infusion period - indicating the development of tolerance. L-NAME-treated animals continuously infused with cocaine showed stimulation thresholds that were not significantly different from saline-treated animals continuously infused with cocaine. A cocaine challenge injection (10 mg/kg, i.p.) administered 3 and again at 10 days following minipump removal revealed that saline-treated animals continuously infused with saline showed lowered BSR thresholds. Saline-treated animals continuously infused with cocaine displayed lowered BSR thresholds that were not significantly different from saline-infused animals. L-NAME treated animals continuously infused with cocaine showed higher BSR thresholds to a challenge 3 days following pump removal. However, stimulation thresholds for this group failed to reach statistical significance on both days (i.e., Days 3 and 10) following pump removal. Results showed that animals continuously infused with cocaine develop robust tolerance to cocaine's threshold-lowering effect during the 14-day infusion period. Tolerance to cocaine's threshold-lowering effect was short-lived and dissipated soon after minipump removal. L-NAME treatment failed to significantly

  18. Altered cocaine-induced behavioral sensitization in adult mice exposed to cocaine in utero.

    PubMed

    Crozatier, Claire; Guerriero, Rejean M; Mathieu, Flavie; Giros, Bruno; Nosten-Bertrand, Marika; Kosofsky, Barry E

    2003-12-30

    Behavioral sensitization induced by psychostimulants is characterized by increased locomotion and stereotypy and may reflect aspects of neuronal adaptations underlying drug addiction in humans. To study the developmental contributions to addictive behaviors, we measured behavioral responses in adult offspring to a cocaine sensitization paradigm following prenatal cocaine exposure. Pregnant Swiss-Webster (SW) mice were injected twice daily from embryonic days 8 to 17 (E8-E17, inclusive) with cocaine (20 or 40 mg/kg/day; COC20 and COC40, respectively), or saline vehicle (SAL and SPF40) subcutaneously (s.c.). A nutritional control group of dams were 'pair-fed' with COC40 dams (SPF40). P120 male offspring from each prenatal treatment group were assigned to a behavioral sensitization group and injected with cocaine (15 mg/kg) or saline intraperitoneally (i.p.) every other day for seven doses. Locomotor activity and stereotypy were measured during habituation, cocaine initiation, and following a cocaine challenge 21 days after the last initiation injection. As expected, animals demonstrated significantly more locomotion and stereotypic behavior following acute and recurrent injection of cocaine compared to saline-injected animals. However, for each prenatal treatment group, cocaine-sensitized animals showed unique temporal profiles for the increase in locomotor sensitization and stereotypy over the course of the sensitization protocol. Two features that distinguished the altered behavioral progression of prenatally cocaine-exposed animals (COC40) from control (SAL) animals included blunted augmentation of locomotion and enhanced patterns of stereotypic behavior. These findings provide evidence that the behavioral activating effects of cocaine in adult animals are altered following exposure to cocaine in utero.

  19. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

    SciTech Connect

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Wang, G.-J.; Tomasi, D.; Telang, F.; Fowler, J.S.; Pradhan, K.; Jayne, M.; Logan, J.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2010-07-01

    Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and {sup 18}FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic

  20. Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.

    PubMed

    Mello, Nancy K; Negus, S Stevens; Knudson, Inge M; Kelly, Maureen; Mendelson, Jack H

    2008-03-01

    The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E(2)beta) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E(2)beta in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose-effect curve determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17beta-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E(2)beta in cyclodextrin and in sesame oil were studied. Acute administration of E(2)beta did not consistently alter the cocaine self-administration or drug discrimination dose-effect curves in comparison to saline control treatment. Females also did not self-administer E(2)beta (0.00001-0.10 mg/kg, i.v.) above saline levels. Finally, E(2)beta (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys. PMID:17507915

  1. Alcohol dependence--classificatory considerations.

    PubMed

    Lesch, O M; Ades, J; Badawy, A; Pelc, I; Sasz, H

    1993-01-01

    The term alcoholism or alcohol dependence has acquired a broad range of meanings. The Plinius Maior Society herewith presents new classificatory considerations and suggests additional recording of special dimensions according to the individual hypothesis and design of a study.

  2. Reactivity to alcohol cues and induced moods in alcoholics.

    PubMed

    Litt, M D; Cooney, N L; Kadden, R M; Gaupp, L

    1990-01-01

    It has been theorized that respondent conditioning processes in part underlie desire for alcohol and thus contribute to relapse after alcoholism treatment. One implication of this theory is that the relevant conditioned responses could be eliminated by respondent extinction, in which the alcoholic patient is exposed to alcohol-related stimuli while being prevented from consuming alcohol. However, exteroceptive cues such as the sight and smell of alcoholic beverages are not always sufficient to elicit desire for alcohol. In view of this, it has been suggested that interoceptive cues, such as mood states, may also play a role in eliciting desire for alcohol. To test this, eight alcoholic subjects were induced to experience negative or neutral moods on four separate days, and then exposed to the sight and smell of their favorite alcoholic drink, and to a neutral stimulus (seltzer water), in a within-subjects design. Results from this work indicate that: (a) negative moods can be reliably induced in the laboratory as confirmed by subjects' reports; (b) exposure to alcohol cues had no effect on desire for alcohol while subjects were in a relaxed, neutral mood state; (c) the presence of negative mood states alone appeared to be sufficient to elicit desire for alcohol in some subjects, regardless of whether alcohol or water was presented. These data argue that negative mood states may cue desire for alcohol independent of other cues. The data also suggest that reactivity to alcohol cues may be substantially reduced by relaxation.

  3. Cocaine addiction: from habits to stereotypical-repetitive behaviors and punding.

    PubMed

    Fasano, Alfonso; Barra, Andrea; Nicosia, Paola; Rinaldi, Federica; Bria, Pietro; Bentivoglio, Anna Rita; Tonioni, Federico

    2008-07-01

    "Punding" is a stereotypical motor behavior characterized by an intense fascination with repetitive handling and examining of objects. Since its first description in amphetamine and cocaine addicts, data on punding has only derived from studies performed in patients with Parkinson's disease (PD). Punding is classifiable as the most severe form of Repetitive Reward-Seeking Behaviours (RRSB) syndromes. The aim of this study was to investigate the occurrence and phenomelogy of RRSB acutely induced by cocaine in order to determine the prevalence, severity and distinctive features discriminating "punders" from "non-punders". A consecutive sample of 50 cocaine addicts received a clinical psychiatric interview. RRSB diagnosis and severity were assessed using a modified version of a previous published questionnaire designed to identify punding in patients with PD. In the present series, 38% of the cocaine addicts met the proposed diagnostic criteria for a RRSB and 8% were considered punders. Subjects with vs. without RRSB did not differ in terms of sex ratio, age, education, occupation, predisposing habits, duration of cocaine use, hours of sleep, comorbid psychiatric disorders, and concomitant use of other drugs. These results and the observation that in the majority of cases RRSB started soon after first drug intake, strongly suggest that an underlying unknown predisposition led to the development of these behaviors. In conclusion, RRSB and punding is much more common than has been described previously and the resultant social disability is often overlooked.

  4. Repeated electrical stimulation of reward-related brain regions affects cocaine but not "natural" reinforcement.

    PubMed

    Levy, Dino; Shabat-Simon, Maytal; Shalev, Uri; Barnea-Ygael, Noam; Cooper, Ayelet; Zangen, Abraham

    2007-12-19

    Drug addiction is associated with long-lasting neuronal adaptations including alterations in dopamine and glutamate receptors in the brain reward system. Treatment strategies for cocaine addiction and especially the prevention of craving and relapse are limited, and their effectiveness is still questionable. We hypothesized that repeated stimulation of the brain reward system can induce localized neuronal adaptations that may either potentiate or reduce addictive behaviors. The present study was designed to test how repeated interference with the brain reward system using localized electrical stimulation of the medial forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC) affects cocaine addiction-associated behaviors and some of the neuronal adaptations induced by repeated exposure to cocaine. Repeated high-frequency stimulation in either site influenced cocaine, but not sucrose reward-related behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas stimulation of the PFC reduced both cocaine-seeking behavior and the motivation for its consumption. The behavioral findings were accompanied by glutamate receptor subtype alterations in the nucleus accumbens and the ventral tegmental area, both key structures of the reward system. It is therefore suggested that repeated electrical stimulation of the PFC can become a novel strategy for treating addiction. PMID:18094257

  5. Cocaine and kappa-opioid withdrawal in Planaria blocked by D-, but not L-, glucose.

    PubMed

    Umeda, Sumiyo; Stagliano, Gregory W; Raffa, Robert B

    2004-08-27

    Planarians (Dugesia dorotocephala) that were exposed for 1 h to cocaine (80 microM) or to the kappa-selective opioid receptor agonist U-50,488H (1 microM) displayed an abstinence-induced withdrawal syndrome, indicative of the development of physical dependence, when they were tested in cocaine- (or U-50,488H-) free water, but not when they were tested in cocaine- (or U-50,488H-) containing water. The withdrawal was manifested as a significant (P<0.05) decrease in the rate of planarian spontaneous locomotor activity over a 5-min observation period, using a recently designed metric. Co-exposure of the planarians to D-glucose (1 microM) or to 2-deoxy-D-glucose (2-DG, 1 microM), but not to L-glucose (1 microM), significantly attenuated (P<0.05) the development of physical dependence, shown by an attenuated withdrawal syndrome, from cocaine and U-50,488H. These results suggest that either D-glucose and 2-deoxy-D-glucose compete with a common cocaine and kappa-opioid transport mechanism or that the development of physical dependence (or the inhibition of abstinence-induced withdrawal) in planarians requires energy supplied from glucose metabolism.

  6. Sex mediates dopamine and adrenergic receptor expression in adult rats exposed prenatally to cocaine

    PubMed Central

    Ferris, Mark J.; Mactutus, Charles F.; Silvers, Janelle M.; Hasselrot, Ulla; Strupp, Barbara J.; Booze, Rosemarie M.

    2010-01-01

    The extent of catecholaminergic receptor and respective behavioral alterations associated with prenatal cocaine exposure varies according to exogenous factors such as the amount, frequency, and route of maternal exposure, as well as endogenous factors such as specific brain regions under consideration and sex of the species. The goal of the current study was to use autoradiography to delineate possible moderators of dopaminergic and adrenergic receptor expression in adult rat offspring exposed to cocaine in utero. The current study demonstrated sex-dependent D1 receptor, α2, and noradrenergic transporter binding alterations in prelimbic, hippocampus, and anterior cingulate regions of adult rat brains exposed to cocaine during gestational days 8–21. Of further interest was the lack of alterations in the nucleus accumbens for nearly all receptors/transporters investigated, as well as the lack of alterations in D3 receptor binding in nearly all of the regions investigated (nucleus accumbens, prelimbic region, hippocampus, and cingulate gyrus). Thus, the current investigation demonstrated persistent receptor and transporter alterations that extend well into adulthood as a result of cocaine exposure in utero. Furthermore, the demonstration that sex played a mediating role in prenatal cocaine-induced, aberrant receptor/transporter expression is of primary importance for future studies that seek to control for sex in either design or analysis. PMID:17933484

  7. Smoked cocaine in socially-depressed areas

    PubMed Central

    2010-01-01

    Background The main objectives of this study are to describe the smoked cocaine user's profile in socially-depressed areas and their needs from a harm-reduction perspective, to investigate their use of smoking crack and compare the acute effects between injecting and smoking consumption. Methods The study took place in SAPS, Barcelona, Spain. Two focus group sessions were undertaken with a total of 8 drug users. Secondly, the 8 participants answered a structured questionnaire and in the course of the sessions, as a snowball activity, were trained to survey 6 other crack smokers. Results We obtained 56 questionnaires. The majority of participants were from non-European Community countries (62.69%), 70.2% of participants referred to sharing the smoking equipment. The most frequent symptoms reported during smoked cocaine were mydriasis (83.33%)), perspiration (72.92%) and compulsive object search (70.83%) During the group sessions, participants said that smoked cocaine is much more addictive than injected cocaine and causes more anxiety. Participants also reported the difficulty of changing from injected use to smoked use, due to the larger amount of cocaine needed to reach the same effects as when having injected. Conclusions We can conclude that the research, focused on achieving greater knowledge of the smoked cocaine user's profile, their usage of smoking crack, consumption patterns and acute effects, should be incorporated into substance misuse interventions. PMID:21059272

  8. Profiling cocaine by ATR-FTIR.

    PubMed

    Marcelo, M C A; Mariotti, K C; Ferrão, M F; Ortiz, R S

    2015-01-01

    In this article, five hundred and thirteen cocaine seizures of the State of Rio Grande do Sul (Brazil) were analyzed by Fourier transform infrared spectroscopy (FT-IR) in the fingerprint region (1800-650 cm(-1)) to profiling and evaluate the pharmaceutical products used as adulterants. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used to identify patterns among the samples whereas partial least square discriminant analysis (PLS-DA) and support vector machines discriminant analysis (SVM-DA) were used to classification the cocaine between base and salt. Spectra of standard solid mixtures of cocaine (salt and base), phenacetin, lidocaine and caffeine were used associated with PCA to predict qualitatively the profile of cocaine seizure. In HCA and PCA, salt and base group were formed correctly. Accordingly with predicted profile of the salt samples, they were majority adulterated with caffeine and lidocaine whereas base cocaine was adulterated only with phenacetin. In the discrimant analysis, all methods have classified the cocaine samples correctly with sensitivity and specificity equal to one between salt and base.

  9. Equipment Design and Cost Estimation for Small Modular Biomass Systems, Synthesis Gas Cleanup, and Oxygen Separation Equipment; Task 9: Mixed Alcohols From Syngas -- State of Technology

    SciTech Connect

    Nexant Inc.

    2006-05-01

    This deliverable is for Task 9, Mixed Alcohols from Syngas: State of Technology, as part of National Renewable Energy Laboratory (NREL) Award ACO-5-44027, ''Equipment Design and Cost Estimation for Small Modular Biomass Systems, Synthesis Gas Cleanup and Oxygen Separation Equipment''. Task 9 supplements the work previously done by NREL in the mixed alcohols section of the 2003 technical report Preliminary Screening--Technical and Economic Assessment of Synthesis Gas to Fuels and Chemicals with Emphasis on the Potential for Biomass-Derived Syngas.

  10. Differential modulation of the discriminative stimulus effects of methamphetamine and cocaine by alprazolam and oxazepam in male and female rats.

    PubMed

    Spence, A L; Guerin, G F; Goeders, N E

    2016-03-01

    Drug users often combine benzodiazepines with psychostimulants, such as methamphetamine. However, very little research has been conducted on this type of polydrug use, particularly in female subjects. The present study was therefore designed to examine the effects of two benzodiazepines, alprazolam and oxazepam, on the discriminative stimulus effects of methamphetamine and cocaine in both male and female rats. Rats were trained to discriminate methamphetamine (1.0 mg/kg, ip) or cocaine (10 mg/kg, ip) from saline using a two-lever operant, food-reinforced, drug discrimination design. Pretreatment with oxazepam (5, 10 and 20 mg/kg, ip) significantly attenuated methamphetamine discrimination in both male and female rats. In contrast, however, the high dose of alprazolam (4 mg/kg, ip) actually augmented the subjective effects of lower doses of methamphetamine (0.125 and 0.25 mg/kg, ip). Oxazepam produced similar effects on the subjective effects of cocaine as with methamphetamine, significantly reducing cocaine discrimination in both male and female rats. However, neither the high nor low dose of alprazolam (2 and 4 mg/kg, ip) produced any apparent effect on cocaine discrimination. Finally, while similar results were observed in both male and female rats across these experiments, methamphetamine and cocaine discrimination were more sensitive to oxazepam in female subjects. The results of these experiments suggest that alprazolam and oxazepam can differentially affect the subjective effects of methamphetamine and cocaine. These results also demonstrate that alprazolam can differentially affect the discriminative stimulus effects of methamphetamine and cocaine.

  11. Behavioral momentum of cocaine self-administration: effects of frequency of reinforcement on resistance to extinction.

    PubMed

    Quick, Stacey L; Shahan, Timothy A

    2009-07-01

    Persistent drug seeking is a defining property of substance abuse and is generally thought to depend, in part, on exposure to drug-associated contexts. Behavioral momentum theory provides a set of methods and a theoretical framework for understanding how stimulus contexts contribute to the persistence of operant behavior. Earlier research has extended behavioral momentum theory to alcohol self-administration, but not to intravenous drug self-administration. This experiment extended behavioral momentum theory to cocaine self-administration by examining the effects of frequency of cocaine reinforcement in a context on resistance to extinction. Rats self-administered 0.32 mg/kg infusions of cocaine in a multiple schedule of reinforcement arranging two distinct contexts. Responding in a Rich context was reinforced by cocaine infusions at a higher frequency (i.e. variable interval 120 s) and in a Lean context at a lower frequency (variable interval 360 s). After establishment of responding in the two contexts, resistance to extinction was examined. Preextinction response rates for cocaine were similar in the Rich and Lean contexts. Nonetheless, relative resistance to extinction was greater in the Rich context than in the Lean context. The difference in resistance to extinction in the two contexts was well described by a quantitative model of behavioral momentum. These results suggest that the frequency of drug reinforcement in a context contributes to the persistence of drug seeking in that context, and that behavioral momentum theory might be useful for understanding how drug-associated contexts contribute to the persistence of drug seeking.

  12. Behavioral momentum of cocaine self-administration: effects of frequency of reinforcement on resistance to extinction.

    PubMed

    Quick, Stacey L; Shahan, Timothy A

    2009-07-01

    Persistent drug seeking is a defining property of substance abuse and is generally thought to depend, in part, on exposure to drug-associated contexts. Behavioral momentum theory provides a set of methods and a theoretical framework for understanding how stimulus contexts contribute to the persistence of operant behavior. Earlier research has extended behavioral momentum theory to alcohol self-administration, but not to intravenous drug self-administration. This experiment extended behavioral momentum theory to cocaine self-administration by examining the effects of frequency of cocaine reinforcement in a context on resistance to extinction. Rats self-administered 0.32 mg/kg infusions of cocaine in a multiple schedule of reinforcement arranging two distinct contexts. Responding in a Rich context was reinforced by cocaine infusions at a higher frequency (i.e. variable interval 120 s) and in a Lean context at a lower frequency (variable interval 360 s). After establishment of responding in the two contexts, resistance to extinction was examined. Preextinction response rates for cocaine were similar in the Rich and Lean contexts. Nonetheless, relative resistance to extinction was greater in the Rich context than in the Lean context. The difference in resistance to extinction in the two contexts was well described by a quantitative model of behavioral momentum. These results suggest that the frequency of drug reinforcement in a context contributes to the persistence of drug seeking in that context, and that behavioral momentum theory might be useful for understanding how drug-associated contexts contribute to the persistence of drug seeking. PMID:19571742

  13. Risk factors for cocaine-induced psychosis in cocaine-dependent patients.

    PubMed

    Roncero, C; Daigre, C; Gonzalvo, B; Valero, S; Castells, X; Grau-López, L; Eiroa-Orosa, F J; Casas, M

    2013-03-01

    Cocaine consumption can induce transient psychotic symptoms, expressed as paranoia or hallucinations. Cocaine induced psychosis (CIP) is common but not developed in all cases. This is the first European study on the relationship between CIP, consumption pattern variables and personality disorders. We evaluated 173 cocaine-dependent patients over 18 years; mostly males, whose average age was 33.6 years (SD=7.8). Patients attending an outpatient addictions department were enrolled in the study and subsequently systematically evaluated using SCID I and SCID II interviews for comorbid disorders, a clinical interview for psychotic symptoms and EuropASI for severity of addiction. A high proportion of cocaine dependent patients reported psychotic symptoms under the influence of cocaine (53.8%), the most frequently reported being paranoid beliefs and suspiciousness (43.9%). A logistic regression analysis was performed, finding that a model consisting of amount of cocaine consumption, presence of an antisocial personality disorder and cannabis dependence history had 66.2% sensitivity 75.8% specificity predicting the presence of CIP. In our conclusions, we discuss the relevance of evaluating CIP in all cocaine dependent-patients, and particularly in those fulfilling the clinical profile derived from our results. These findings could be useful for a clinical approach to the risks of psychotic states in cocaine-dependent patients.

  14. DNA nanostructure-decorated surfaces for enhanced aptamer-target binding and electrochemical cocaine sensors.

    PubMed

    Wen, Yanli; Pei, Hao; Wan, Ying; Su, Yan; Huang, Qing; Song, Shiping; Fan, Chunhai

    2011-10-01

    The sensitivity of aptamer-based electrochemical sensors is often limited by restricted target accessibility and surface-induced perturbation of the aptamer structure, which arise from imperfect packing of probes on the heterogeneous and locally crowded surface. In this study, we have developed an ultrasensitive and highly selective electrochemical aptamer-based cocaine sensor (EACS), based on a DNA nanotechnology-based sensing platform. We have found that the electrode surface decorated with an aptamer probe-pendant tetrahedral DNA nanostructure greatly facilitates cocaine-induced fusion of the split anticocaine aptamer. This novel design leads to a sensitive cocaine sensor with a remarkably low detection limit of 33 nM. It is also important that the tetrahedra-decorated surface is protein-resistant, which not only suits the enzyme-based signal amplification scheme employed in this work, but ensures high selectivity of this sensor when deployed in sera or other adulterated samples.

  15. Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotine+cocaine self-administration.

    PubMed

    Mello, Nancy K; Fivel, Peter A; Kohut, Stephen J; Carroll, F Ivy

    2014-04-01

    Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at α4β2* and α6β2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at α7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine+cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatta). Varenicline (0.004-0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7-10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding returned to baseline. During control treatment, nicotine+cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P<0.05-0.001). Varenicline dose-dependently reduced responding maintained by nicotine alone (0.0032 mg/kg/inj) (P<0.05), and in combination with cocaine (0.0032 mg/kg/inj) (P<0.05) with no significant effects on food-maintained responding. However, varenicline did not significantly decrease self-administration of a low dose of nicotine (0.001 mg/kg), cocaine alone (0.0032 and 0.01 mg/kg/inj), or 0.01 mg/kg cocaine combined with the same doses of nicotine. We conclude that varenicline selectively attenuates the reinforcing effects of nicotine alone but not cocaine alone, and its effects on nicotine+cocaine combinations are dependent on the dose of cocaine. PMID:24304823

  16. Prolonged withdrawal following cocaine self-administration increases resistance to punishment in a cocaine binge

    PubMed Central

    Gancarz-Kausch, Amy M.; Adank, Danielle N.; Dietz, David M.

    2014-01-01

    Drug addiction is characterized by compulsive drug-taking behaviors and a high propensity to relapse following drug cessation. Drug craving and seeking can increase during a period of abstinence, but this phenomenon is not observed in drug-induced reinstatement models. To investigate the effect of withdrawal on cocaine relapse, rats were exposed to extended-access cocaine self-administration and subjected to either 1 or 30 d of withdrawal. When tested during 12 h unlimited access to cocaine (binge), the duration of the withdrawal did not influence cocaine intake. However, using a histamine punishment procedure that greatly suppresses drug-taking behavior, we demonstrate that longer periods of abstinence from cocaine induce a greater persistence in responding for drug in the face of negative consequences. PMID:25363133

  17. Prolonged withdrawal following cocaine self-administration increases resistance to punishment in a cocaine binge.

    PubMed

    Gancarz-Kausch, Amy M; Adank, Danielle N; Dietz, David M

    2014-11-03

    Drug addiction is characterized by compulsive drug-taking behaviors and a high propensity to relapse following drug cessation. Drug craving and seeking can increase during a period of abstinence, but this phenomenon is not observed in drug-induced reinstatement models. To investigate the effect of withdrawal on cocaine relapse, rats were exposed to extended-access cocaine self-administration and subjected to either 1 or 30 d of withdrawal. When tested during 12 h unlimited access to cocaine (binge), the duration of the withdrawal did not influence cocaine intake. However, using a histamine punishment procedure that greatly suppresses drug-taking behavior, we demonstrate that longer periods of abstinence from cocaine induce a greater persistence in responding for drug in the face of negative consequences.

  18. Cocaine

    MedlinePlus

    ... amounts to build up between nerve cells. This flood of dopamine ultimately disrupts normal brain communication and ... in brain circuits controlling pleasure and movement. This flood of dopamine ultimately disrupts normal brain communication and ...

  19. Temporal Pattern of Cocaine Intake Determines Tolerance vs Sensitization of Cocaine Effects at the Dopamine Transporter

    PubMed Central

    Calipari, Erin S; Ferris, Mark J; Zimmer, Benjamin A; Roberts, David CS; Jones, Sara R

    2013-01-01

    The dopamine transporter (DAT) is responsible for terminating dopamine (DA) signaling and is the primary site of cocaine's reinforcing actions. Cocaine self-administration has been shown previously to result in changes in cocaine potency at the DAT. To determine whether the DAT changes associated with self-administration are due to differences in intake levels or temporal patterns of cocaine-induced DAT inhibition, we manipulated cocaine access to produce either continuous or intermittent elevations in cocaine brain levels. Long-access (LgA, 6 h) and short-access (ShA, 2 h) continuous self-administration produced similar temporal profiles of cocaine intake that were sustained throughout the session; however, LgA had greater intake. ShA and intermittent-access (IntA, 6 h) produced the same intake, but different temporal profiles, with ‘spiking' brain levels in IntA compared with constant levels in ShA. IntA consisted of 5-min access periods alternating with 25-min timeouts, which resulted in bursts of high responding followed by periods of no responding. DA release and uptake, as well as the potency of cocaine for DAT inhibition, were assessed by voltammetry in the nucleus accumbens slices following control, IntA, ShA, and LgA self-administration. Continuous-access protocols (LgA and ShA) did not change DA parameters, but the ‘spiking' protocol (IntA) increased both release and uptake of DA. In addition, high continuous intake (LgA) produced tolerance to cocaine, while ‘spiking' (IntA) produced sensitization, relative to ShA and naive controls. Thus, intake and pattern can both influence cocaine potency, and tolerance seems to be produced by high intake, while sensitization is produced by intermittent temporal patterns of intake. PMID:23719505

  20. Functional Consequences of Cocaine Re-exposure after Discontinuation of Cocaine Availability

    PubMed Central

    Beveridge, Thomas J.R.; Smith, Hilary R.; Nader, Susan H.; Nader, Michael A.; Porrino, Linda J.

    2014-01-01

    Cocaine users exhibit a wide range of behavioral impairments accompanied by brain structural, neurochemical and functional abnormalities. Metabolic mapping studies in cocaine users and animal models have shown extensive functional alterations throughout the striatum, limbic system, and cortex. Few studies, however, have evaluated the persistence of these effects following cessation of cocaine availability. The purpose of this study, therefore, was to assess the functional effects of re-exposure to cocaine in nonhuman primates after the discontinuation of cocaine self-administration for 30 or 90 days, using the quantitative autoradiographic 2-[14C]deoxyglucose (2DG) method. Rhesus monkeys self-administered cocaine (fixed interval 3-min schedule, 30 infusions per session, 0.3 mg/kg/infusion) for 100 sessions followed by 30 (n=4) or 90 days (n=3) during which experimental sessions were not conducted. Food-reinforced control animals (n=5) underwent identical schedules of reinforcement. Animals were then re-exposed to cocaine or food for one final session and the 2DG method applied immediately after session completion. Compared to controls, re-exposure to cocaine after 30 or 90 day drug-free periods resulted in lower rates of glucose utilization in ventral and dorsal striatum, prefrontal and temporal cortex, limbic system, thalamus, and midbrain. These data demonstrate that vulnerability to the effects of cocaine persists for as long as 90 days after cessation of drug use. While there was some evidence for recovery (fewer brain areas were affected by cocaine re-exposure at 90 days as compared to 30 days), this was not uniform across regions, thus suggesting that recovery occurs at different rates in different brain systems. PMID:24953829

  1. Functional consequences of cocaine re-exposure after discontinuation of cocaine availability.

    PubMed

    Beveridge, Thomas J R; Smith, Hilary R; Nader, Susan H; Nader, Michael A; Porrino, Linda J

    2014-10-01

    Cocaine users exhibit a wide range of behavioral impairments accompanied by brain structural, neurochemical and functional abnormalities. Metabolic mapping studies in cocaine users and animal models have shown extensive functional alterations throughout the striatum, limbic system, and cortex. Few studies, however, have evaluated the persistence of these effects following cessation of cocaine availability. The purpose of this study, therefore, was to assess the functional effects of re-exposure to cocaine in nonhuman primates after the discontinuation of cocaine self-administration for 30 or 90 days, using the quantitative autoradiographic 2-[14C]deoxyglucose (2DG) method. Rhesus monkeys self-administered cocaine (fixed interval 3-min schedule, 30 infusions per session, 0.3 mg/kg/infusion) for 100 sessions followed by 30 (n=4) or 90 days (n=3) during which experimental sessions were not conducted. Food-reinforced control animals (n=5) underwent identical schedules of reinforcement. Animals were then re-exposed to cocaine or food for one final session and the 2DG method applied immediately after session completion. Compared to controls, re-exposure to cocaine after 30 or 90 day drug-free periods resulted in lower rates of glucose utilization in ventral and dorsal striatum, prefrontal and temporal cortex, limbic system, thalamus, and midbrain. These data demonstrate that vulnerability to the effects of cocaine persists for as long as 90 days after cessation of drug use. While there was some evidence for recovery (fewer brain areas were affected by cocaine re-exposure at 90 days as compared to 30 days), this was not uniform across regions, thus suggesting that recovery occurs at different rates in different brain systems. PMID:24953829

  2. Predictors of Violence Following Emergency Department Visit for Cocaine-Related Chest Pain

    PubMed Central

    Walton, Maureen A.; Cunningham, Rebecca; Chermack, Stephen T.; Tripathi, Shanti; Weber, James; Maio, Ronald F.; Booth, Brenda M.

    2009-01-01

    binge drinking being a consistent marker of continued violence involvement. Intervention approaches to link these not-in-treatment cocaine users to services and reduce cocaine use must take into account concomitant alcohol misuse and violence. PMID:18722724

  3. Cocaine and metabolites by LC-MS/MS.

    PubMed

    Snozek, Christine L H; Bjergum, Matthew W; Langman, Loralie J

    2012-01-01

    Abuse of the stimulant cocaine (COC) is a common problem in the United States and elsewhere. The drug can be used either as the powder or as the free base (crack COC), and causes feelings of alertness and euphoria; both forms of COC are powerfully addictive. The assay described here is designed to detect and quantitate parent COC, its major metabolite benzoylecgonine, and a selection of metabolites that can provide specific information about sample validity (m-hydroxybenzoylecgonine), potential toxicity (norcocaine), route of administration (anhydroecgonine methyl ester), and co-utilization with ethanol (cocaethylene). PMID:22767110

  4. The Association between Prenatal Cocaine Exposure and Physiological Regulation at 13 Months of Age

    ERIC Educational Resources Information Center

    Schuetze, Pamela; Eiden, Rina D.; Danielewicz, Susan

    2009-01-01

    Background: This study examined the association between prenatal cocaine exposure (PCE) and autonomic regulation at 13 months of age. Methods: Measures of respiratory sinus arrhythmia (RSA) were obtained from 156 (79 exposed, and 77 nonexposed) infants during baseline and during tasks designed to elicit positive (PA) and negative affect (NA).…

  5. Design and Evaluation of an Alcohol and Other Drug Abuse Prevention Program for High Risk Families with Preschool Children.

    ERIC Educational Resources Information Center

    Powers, Stephen; And Others

    In fall, 1991, La Frontera Center, the Tucson Council for Alcohol and Drug Dependence, and the Community Organization for Drug Abuse Control were funded to carry out an educational program to reduce alcohol and other drug abuse in the Tucson, Arizona area. The resulting project, Pasos Adelante (Steps Forward), is an early intervention…

  6. The stereotypy-inducing and OCD-like effects of chronic ‘binge’ cocaine are modulated by distinct subtypes of nicotinic acetylcholine receptors

    PubMed Central

    Metaxas, A; Keyworth, HL; Yoo, JH; Chen, Y; Kitchen, I; Bailey, A

    2012-01-01

    BACKGROUND AND PURPOSE High rates of cigarette smoking occur in cocaine-dependent individuals, reflecting an involvement of nicotinic acetylcholine receptors (nAChRs) in cocaine-elicited behaviour. This study was designed to assess the contribution of different nAChR subtypes to the behavioural and neurochemical effects of chronic cocaine treatment. EXPERIMENTAL APPROACH Cocaine (15 mg·kg−1, i.p.) was administered to male C57BL/6J mice in a chronic ‘binge’ paradigm, with and without the coadministration of the α7 preferring nAChR antagonist methyllycaconitine (MLA; 5 mg·kg−1, i.p.) or the β2* nAChR antagonist dihydro-β-erythroidine (DHβE; 2 mg·kg−1, i.p.). Quantitative autoradiography was used to examine the effect of cocaine exposure on α7 and α4β2* nAChRs, and on the high-affinity choline transporter. KEY RESULTS MLA+cocaine administration induced an intense self-grooming behaviour, indicating a likely role for α7 nAChRs in modulating this anxiogenic, compulsive-like effect of cocaine. In the major island of Calleja, a key area of action for neuroleptics, MLA+cocaine reduced choline transporter binding compared with cocaine (with or without DHβE) administration. DHβE treatment prevented the induction of stereotypy sensitisation to cocaine but prolonged locomotor sensitisation, implicating heteromeric β2* nAChRs in the neuroadaptations mediating cocaine-induced behavioural sensitisation. ‘Binge’ cocaine treatment region-specifically increased α4β2* nAChR binding in the midbrain dopaminergic regions: ventral tegmental area and substantia nigra pars compacta. CONCLUSIONS AND IMPLICATIONS We have shown a differential, subtype-selective, contribution of nAChRs to the behavioural and neurochemical sequelae of chronic cocaine administration. These data support the clinical utility of targeting specific nAChR subtypes for the alleviation of cocaine-abuse symptomatology. PMID:22568685

  7. Myths about drinking alcohol

    MedlinePlus

    ... to. I spend a lot of time getting alcohol, drinking alcohol, or recovering from the effects of alcohol. ... Institute on Alcohol Abuse and Alcoholism. Overview of Alcohol Consumption. www.niaaa.nih.gov/alcohol-health/overview-alcohol- ...

  8. The first universal opioid ligand, (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028): characterization of the in vitro profile and in vivo behavioral effects in mouse models of acute pain and cocaine-induced reward.

    PubMed

    Khroyan, Taline V; Polgar, Willma E; Cami-Kobeci, Gerta; Husbands, Stephen M; Zaveri, Nurulain T; Toll, Lawrence

    2011-03-01

    Certain behavioral features of buprenorphine, including a bell-shaped curve for antinociception and attenuation of alcohol consumption, are thought to be mediated by activation of nociceptin/orphanin FQ peptide (NOP) receptors, despite moderate affinity and low efficacy at NOP receptors. We hypothesized that ligands with buprenorphine's physical properties, but possessing increased NOP receptor affinity and efficacy, would improve the profile as a drug abuse medication and reduce addiction liability. Using this strategy, we designed several compounds with universally high affinity, i.e., less than 10 nM at μ, δ, κ, and NOP receptors. Among these, (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6-methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028) has high affinity at all opioid receptors and increased NOP receptor efficacy in vitro in the [³⁵S]GTPγS binding assay, however, while still being a partial agonist. In vivo, BU08028 was evaluated in an acute thermal antinociception assay, for its ability to induce conditioned place preference (CPP), and for its effect on cocaine-induced CPP. BU08028 is a very potent long-lasting analgesic. It produces an increase in locomotor activity and a significant CPP. As a pretreatment to cocaine, BU08028 does not alter cocaine CPP but causes a further increase in cocaine-induced locomotor activity. The analgesic, rewarding, and stimulant effects are probably caused by μ receptor stimulation. It is likely that with BU08028, a partial agonist at both NOP and μ receptors, μ-mediated activity overpowers NOP-mediated effects. Thus, it is possible that a different buprenorphine analog that is a universal high-affinity opioid ligand but with "full agonist" activity at NOP may counteract traditional opioid-mediated effects such as antinociception and reward.

  9. Solid-state probe based electrochemical aptasensor for cocaine: a potentially convenient, sensitive, repeatable, and integrated sensing platform for drugs.

    PubMed

    Du, Yan; Chen, Chaogui; Yin, Jianyuan; Li, Bingling; Zhou, Ming; Dong, Shaojun; Wang, Erkang

    2010-02-15

    Aptamers, which are artificial oligonucleotides selected in vitro, have been employed to design novel biosensors (i.e., aptasensors). In this work, we first constructed a label-free electrochemical aptasensor introducing a probe immobilization technique by the use of a layer-by-layer (LBL) self-assembled multilayer with ferrocene-appended poly(ethyleneimine) (Fc-PEI) on an indium tin oxide (ITO) array electrode for detection of cocaine. The Fc-PEI and gold nanoparticles (AuNPs) were LBL assembled on the electrode surface via electrostatic interaction. Then, cocaine aptamer fragments, SH-C2, were covalently labeled onto the outermost AuNP layer. When the target cocaine and cocaine aptamer C1 were present simultaneously, the SH-C2 layer hybridized partly with C1 to bind the cocaine, which led to a decreased differential pulse voltammetry (DPV) signal of Fc-PEI. This DPV signal change could be used to sensitively detect cocaine with the lowest detectable concentration down to 0.1 microM and the detection range up to 38.8 microM, which falls in the the expected range for medical use of detecting drug abuse involving cocaine. Meanwhile, the sensor was specific to cocaine in complex biologic fluids such as human plasma, human saliva, etc. The sensing strategy had general applicability, and the detection of thrombin could also be realized, displayed a low detection limit, and exhibited worthiness to other analytes. The aptasensor based on the array electrode held promising potential for integration of the sensing ability in multianalysis for simultaneous detection.

  10. Pharmacokinetics of Cocaine and Metabolites in Human Oral Fluid and Correlation with Plasma Concentrations following Controlled Administration

    PubMed Central

    Scheidweiler, Karl B.; Kolbrich Spargo, Erin A.; Kelly, Tamsin L.; Cone, Edward J.; Barnes, Allan J.; Huestis, Marilyn A.

    2011-01-01

    Oral fluid is an attractive alternative matrix for drug testing, with a non-invasive and directly observed collection, but there are few controlled cocaine administration studies to guide interpretation. Materials and Methods While residing on a closed research unit for up to 10 weeks under constant medical supervision, 19 participants were administered 75 mg/70 kg subcutaneous cocaine and 14 received 150mg/70 kg. The disposition of cocaine, benzoylecgonine (BE) and ecgonine methyl ester (EME) into oral fluid was determined by gas chromatography-mass spectrometry for 0.08–48h after administration. Results In oral fluid collected by citric acid candy stimulated expectoration, cocaine first appeared in oral fluid 0.08–0.32h after dosing and was rapidly eliminated with half-lives of 1.1–3.8h. BE and EME were first detected 0.08–1.0h after dosing, with longer half-lives of 3.4–13.8 (BE) and 2.4–15.5h (EME) (p<0.05). Oral fluid and plasma concentrations were significantly correlated for cocaine, BE and EME (p<0.0001). There were no significant differences (p>0.05) in first and last detection times with the 8 μg/L cutoff proposed by the Substance Abuse and Mental Health Services Administration or the 10 μg/L cutoff from the European initiative, Driving Under the Influence of Drugs, Alcohol and Medicines. Metabolite:cocaine ratios increased after cocaine administration, potentially helpful for interpreting time of last use. Comparison of oral fluid collection via citric acid candy stimulated expectoration, citric acid treated Salivette® and neutral cotton Salivette® devices did not reveal significant differences between devices for areas under the curve for cocaine, BE or EME (p>0.05). Discussion and Conclusion These results provide additional evidence for interpreting cocaine and metabolite concentrations in oral fluid and oral fluid’s usefulness as an alternative matrix for drug testing. PMID:20814350

  11. A PLACEBO CONTROLLED TRIAL OF MEMANTINE FOR COCAINE DEPENDENCE WITH HIGH-VALUE VOUCHER INCENTIVES DURING A PRE-RANDOMIZATION LEAD-IN PERIOD

    PubMed Central

    Bisaga, Adam; Aharonovich, Efrat; Cheng, Wendy Y.; Levin, Frances R.; Mariani, John J; Raby, Wilfrid N.; Nunes, Edward V.

    2010-01-01

    Preclinical findings suggest that the inhibition of NMDA glutamatergic neurotransmission may have beneficial effects in the treatment of cocaine dependence. We hypothesized that memantine, a low potency, uncompetitive NMDA receptor antagonist, would be safe and effective in the treatment of cocaine dependence, particularly in preventing relapse to cocaine use in abstinent individuals. Cocaine dependent patients (N =112) were enrolled. The trial began with a 2-week placebo lead-in period during which patients received high-value voucher contingency management to induce abstinence. Participants were then randomized to receive either memantine 20 mg bid (N=39) or placebo (N=42) for 12-weeks in combination with individual relapse-prevention therapy. The randomization was stratified by abstinence status during the lead-in period. The primary outcome was the weekly proportion of days of cocaine use. There were no significant differences in cocaine use outcome between the groups treated with memantine versus placebo. Thus, the efficacy of memantine 40 mg/d for the treatment of cocaine dependence was not supported. Urine-confirmed abstinence during the lead-in period was achieved by 44% of participants, and was a strong predictor of subsequent cocaine abstinence during the trial. This suggests that this clinical trial design, an intensive behavioral intervention during a lead-in period, resolves cocaine dependent patients into two subgroups, one that rapidly achieves sustained abstinence and may not need a medication, and another that displays persistent cocaine use and would most likely benefit from a medication to help induce abstinence. Targeting the latter subgroup may advance medication development efforts. PMID:20537812

  12. Fast quantification of ethanol in whole blood specimens by the enzymatic alcohol dehydrogenase method. Optimization by experimental design.

    PubMed

    Kristoffersen, Lena; Skuterud, Bjørn; Larssen, Bente R; Skurtveit, Svetlana; Smith-Kielland, Anne

    2005-01-01

    A sensitive, fast, simple, and high-throughput enzymatic method for the quantification of ethanol in whole blood (blood) on Hitachi 917 is presented. Alcohol dehydrogenase (ADH) oxidizes ethanol to acetaldehyde using the coenzyme nicotinamide adenine dinucleotide (NAD), which is concurrently reduced to form NADH. Method development was performed with the aid of factorial design, varying pH, and concentrations of NAD+ and ADH. The linear range increased and reaction end point decreased with increasing NAD+ concentration and pH. The method was linear in the concentration range 0.0024-0.4220 g/dL. The limits of detection and quantification were 0.0007 g/dL and 0.0024 g/dL, respectively. Relative standard deviations for the repeatability and within-laboratory reproducibility were in the ranges 0.7-5.7% and 1.6-8.9%, respectively. The correlation coefficient when compared with headspace gas chromatography-flame ionization detection methods was 0.9903. Analysis of authentic positive blood specimens gave results that were slightly lower than those of the reference method.

  13. Stealing and dealing: cocaine and property crimes.

    PubMed

    Hunt, D

    1991-01-01

    A common thread in all studies of this nature is the level of use of cocaine and/or the concomitant use of other drugs, suggesting that economic necessity plays a role in the decision to commit crimes to help defray the costs of use. While a truly causal link between use and crime activity in marginal income populations is apparent. Whether that association is driven primarily by economics or lifestyle considerations is not answered by simple examination of the numbers. Statistically, the use of cocaine is related to criminal activity as a function of the income level and prior criminal experience of the user. This relationship is better defined by looking at the threshold effect in marginal income groups, where use that goes beyond what the pocket can bear produces a significantly greater chance that illegal sources will be found. However, many occasional users or even regular users with resources are able to fund their use through routine sources and never resort to criminal activity or to unconventional financial resources. A large number of cocaine users probably fall into this middle ground: they are neither the "high rollers" that often make the media nor the traditional heroin/cocaine addicts. For them, criminal activity may surface when use exceeds funds or not at all. For still others, cocaine is part of a criminal lifestyle rather than a motivation for it. Statistically, all these cocaine users look the same, though the relationship between their use and their crime may be quite varied. The descriptions of three cases discussed in an earlier paper (Hunt et al. 1985) clarify this point. The first case was a 32-year-old white male former heroin addict and former drug dealer who reported cocaine use intravenously three to four times a month, smoked marijuana weekly, and used no other drugs. He was married, working, and had a small child. He also reported dealing in stolen merchandise and clothing that he got from someone else to sell. This pattern had been

  14. A novel electrochemical aptasensor based on single-walled carbon nanotubes, gold electrode and complimentary strand of aptamer for ultrasensitive detection of cocaine.

    PubMed

    Taghdisi, Seyed Mohammad; Danesh, Noor Mohammad; Emrani, Ahmad Sarreshtehdar; Ramezani, Mohammad; Abnous, Khalil

    2015-11-15

    Cocaine is a strong central nervous system stimulant and one of the most commonly abused drugs. In this study, an electrochemical aptasensor was designed for sensitive and selective detection of cocaine, based on single-walled carbon nanotubes (SWNTs), gold electrode and complimentary strand of aptamer (CS). This electrochemical aptasensor inherits properties of SWNTs and gold such as large surface area and high electrochemical conductivity, as well as high affinity and selectivity of aptamer toward its target and the stronger interaction of SWNTs with single-stranded DNA (ssDNA) than double-stranded DNA (dsDNA). In the absence of cocaine, a little amount of SWNTs bind to Aptamer-CS-modified electrode, so that the electrochemical signal is weak. In the presence of cocaine, aptamer binds to cocaine, leaves the surface of electrode. So that, a large amount of SWNTs bind to CS-modified electrode, generating to a strong electrochemical signal. The designed electrochemical aptasensor showed good selectivity toward cocaine with a limit of detection (LOD) as low as 105 pM. Moreover, the fabricated electrochemical aptasensor was successfully applied to detect cocaine in serum with a LOD as low as 136 pM.

  15. Examination of cocaine dose in a preclinical model of natural reward devaluation by cocaine.

    PubMed

    Green, Jennifer L; Dykstra, Linda A; Carelli, Regina M

    2015-06-01

    In a preclinical model of natural reward devaluation by cocaine, taste cues elicit aversive taste reactivity when they predict impending but delayed cocaine self-administration. Here, we investigated this negative affective state as a function of cocaine dose. Male, Sprague-Dawley rats were given 45 brief intraoral infusions of a 0.15% saccharin solution before 2 h cocaine self-administration for 14 days. Rats were video recorded; taste reactivity and patterns of self-administration were quantified on the first and last days. On day 14, a significant decrease in appetitive taste reactivity and increase in aversive taste reactivity was observed (compared with day 1) that did not vary as a function of cocaine dose. In contrast, patterns of cocaine self-administration (i.e. the total number of lever presses and load-up behavior) varied as a function of dose across days. Further, load-up behavior was positively correlated with aversive taste reactivity (i.e. gapes) on day 14 across all doses tested. Collectively, these findings indicate that the emergence of negative affect in this preclinical model is not dependent on cocaine dose. PMID:25738759

  16. Cognitive Impairment in Acute Cocaine Withdrawal

    PubMed Central

    Kelley, Brendan J.; Yeager, Kenneth R.; Pepper, Tom H.; Beversdorf, David Q.

    2005-01-01

    Objective To perform a pilot study to examine a range of cognitive flexibility tasks early in cocaine withdrawal. Background Previous neuropsychological investigations of cocaine withdrawal have conflicted regarding whether impaired cognitive flexibility occurs. However, most studies have examined patients later in withdrawal. Anxiety and yohimbine-induced panic are greatest early in withdrawal, and both anxiety and increased noradrenergic tone can impair cognitive flexibility. Method Twelve patients acutely withdrawing from cocaine were compared with gender-, age-, and estimated premorbid intelligence–matched control subjects on tests of cognitive flexibility as well as verbal fluency, verbal memory, spatial memory, and attention. Results As predicted, impairments were found on the cognitive flexibility tasks. Impairments also were present in verbal fluency and verbal memory but not spatial memory or attention. Conclusions We propose that the cognitive flexibility impairment may relate to the increased noradrenergic activation recently described in cocaine withdrawal. Impairments on verbal tasks may also relate to an impaired flexibility in the search of semantic networks. Further research will explore the effects of pharmacologic manipulation of the noradrenergic system on cognition in acute withdrawal. Recently, propranolol has been shown to benefit patients in cocaine withdrawal. Further research will explore whether impaired cognitive flexibility related to altered noradrenergic tone could serve as a mechanism for this treatment response. PMID:15970730

  17. Internally concealed cocaine: analytical and diagnostic aspects.

    PubMed

    Bogusz, M J; Althoff, H; Erkens, M; Maier, R D; Hofmann, R

    1995-09-01

    Thirty persons arrested at Frankfurt airport for smuggling internally concealed cocaine in 1993/1994 were investigated. An X-ray examination (in all 30 cases), immunochemical examination of urine (in 27 cases) and of saliva (in 20 cases) was performed in parallel. An X-ray examination gave positive results in all examined persons. EMIT cocaine metabolite assay (cut off 300 ng benzoylecgonine (BE)/mL) was positive in eight urine samples. After reducing the cut off to 150 ng BE/mL urine, eleven samples were classified as positive. The results were confirmed by means of chromatographic determinations. These findings showed limited role of immunological examination of urine as a screening test in suspected smuggling of internally concealed drugs. All saliva samples showed negative immunochemical results. The number of concealed containers ranged from 44 to 135 per person. The amount of cocaine hydrochloride found in particular cases ranged from 242 to 1050 g net weight, divided into containers weighing from 5.7 to 13.8 g. Drug packages were obviously machine-made. The packages smuggled by a particular person were uniform. However, a distinct interpersonal variability in drug packages was observed, in regard to the number of protective layers (4-7), size, weight, and cocaine purity. This may be helpful for the identification of production site. The leaching of cocaine from selected containers was investigated in a stirring bath and was independent of the conditions applied. PMID:7595327

  18. Novel pharmacotherapeutic treatments for cocaine addiction

    PubMed Central

    2011-01-01

    Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there are no approved medications for the treatment of this devastating illness, and behavioral interventions have proven to be of limited use. However, there have been a number of recent trials testing promising agents including dopamine agonists, GABAergic medications and the cocaine vaccine. Here we discuss the most recent human clinical trials of potential medications for treatment of cocaine dependence, as well as pre-clinical studies for another promising agent, levo tetrahydropalmatine. Examination of these recent findings shows promise for GABAergic medications and the cocaine vaccine, as well as unique medications such as disulfiram, whose mechanism remains to be determined. Future work may also confirm specific subgroups of patients for treatment response based on clinical characteristics, biomarkers and pharmacogenetics. This review highlights the need for further, bigger studies in order to determine optimal clinical usage. PMID:22047090

  19. Alcohol Intake and Serum Glucose Levels from the Perspective of a Mendelian Randomization Design: The KCPS-II Biobank

    PubMed Central

    Jee, Yon Ho; Lee, Sun Ju; Jee, Sun Ha

    2016-01-01

    Background Previous studies have suggested that alcohol intake is associated with increased fasting serum glucose (FSG), but the nature of the relationship remains unknown. We used Mendelian randomization analysis to assess the causal effect of alcohol intake on FSG in a middle-aged Korean population. Methods Clinical data including FSG and alcohol intake were collected from 156,386 Koreans aged 20 years or older who took part in the Korean Cancer Prevention Study-II (KCPS-II) Biobank Cohort. The single nucleotide polymorphism rs671 in ALDH2 was genotyped among 2,993 men and 1,374 women in 2016. This was a randomly selected subcohort of KCPS-II Biobank participants. Results Alcohol consumption was positively associated with FSG level in men, but not in women. The rs671 major G allele was associated with increased alcohol intake (F-statistic = 302.62) and an increase in FSG in men. Using Mendelian randomization analysis, alcohol intake increased FSG by 1.78 mg/dL per alcohol unit (10 g ethanol) per day (95% CI: 0.97–2.59) in men. The associations became stronger when we excluded heavy drinkers and the elderly. However, in women, no significant association between rs671 and alcohol or serum glucose was found. Conclusion Using Mendelian randomization analysis, we suggest a causal relationship between alcohol intake and FSG among Korean men. Moreover, we found that the ALDH2 variant rs671 was not associated with FSG among Korean women. PMID:27632197

  20. Enantiodivergent Fluorination of Allylic Alcohols: Data Set Design Reveals Structural Interplay between Achiral Directing Group and Chiral Anion.

    PubMed

    Neel, Andrew J; Milo, Anat; Sigman, Matthew S; Toste, F Dean

    2016-03-23

    Enantioselectivity values represent relative rate measurements that are sensitive to the structural features of the substrates and catalysts interacting to produce them. Therefore, well-designed enantioselectivity data sets are information rich and can provide key insights regarding specific molecular interactions. However, if the mechanism for enantioselection varies throughout a data set, these values cannot be easily compared. This premise, which is the crux of free energy relationships, exposes a challenging issue of identifying mechanistic breaks within multivariate correlations. Herein, we describe an approach to addressing this problem in the context of a chiral phosphoric acid catalyzed fluorination of allylic alcohols using aryl boronic acids as transient directing groups. By designing a data set in which both the phosphoric and boronic acid structures were systematically varied, key enantioselectivity outliers were identified and analyzed. A mechanistic study was executed to reveal the structural origins of these outliers, which was consistent with the presence of several mechanistic regimes within the data set. While 2- and 4-substituted aryl boronic acids favored the (R)-enantiomer with most of the studied catalysts, meta-alkoxy substituted aryl boronic acids resulted in the (S)-enantiomer when used in combination with certain (R)-phosphoric acids. We propose that this selectivity reversal is the result of a lone pair-π interaction between the substrate ligated boronic acid and the phosphate. On the basis of this proposal, a catalyst system was identified, capable of producing either enantiomer in high enantioselectivity (77% (R)-2 to 92% (S)-2) using the same chiral catalyst by subtly changing the structure of the achiral boronic acid.

  1. Cocaine induces state-dependent learning of sexual conditioning in male Japanese quail.

    PubMed

    Gill, Karin E; Rice, Beth Ann; Akins, Chana K

    2015-01-01

    State dependent learning effects have been widely studied in a variety of drugs of abuse. However, they have yet to be studied in relation to sexual motivation. The current study investigated state-dependent learning effects of cocaine in male Japanese quail (Coturnix japonica) using a sexual conditioning paradigm. Cocaine-induced state-dependent learning effects were investigated using a 2×2 factorial design with training state as one factor and test state as the other factor. During a 14-day training phase, male quail were injected once daily with 10mg/kg cocaine or saline and then placed in a test chamber after 15min. In the test chamber, sexual conditioning trials consisted of presentation of a light conditioned stimulus (CS) followed by sexual reinforcement. During the state dependent test, half of the birds received a shift in drug state from training to testing (Coc→Sal or Sal→Coc) while the other half remained in the same drug state (Coc→Coc or Sal→Sal). Results showed that male quail that were trained and tested in the same state (Coc→Coc or Sal→Sal) showed greater sexual conditioning than male quail that were trained and tested in different states (Sal→Coc) except when cocaine was administered chronically prior to the test (Coc→Sal). For the latter condition, sexual conditioning persisted from cocaine training to the saline test. The findings suggest that state dependent effects may alter sexual motivation and that repeated exposure to cocaine during sexual activity may increase sexual motivation which, in turn, may lead to high risk sexual activities. An alternative explanation for the findings is also discussed.

  2. Cocaine induces state-dependent learning of sexual conditioning in male Japanese quail

    PubMed Central

    Gill, Karin E.; Rice, Beth Ann; Akins, Chana K.

    2014-01-01

    State dependent learning effects have been widely studied in a variety of drugs of abuse. However, they have yet to be studied in relation to sexual motivation. The current study investigated state-dependent learning effects of cocaine in male Japanese quail (Coturnix japonica) using a sexual conditioning paradigm. Cocaine-induced state-dependent learning effects were investigated using a 2 × 2 factorial design with training state as one factor and test state as the other factor. During a 14-day training phase, male quail were injected once daily with 10 mg/kg cocaine or saline and then placed in a test chamber after 15 min. In the test chamber, sexual conditioning trials consisted of presentation of a light conditioned stimulus (CS) followed by sexual reinforcement. During the state dependent test, half of the birds received a shift in drug state from training to testing (Coc → Sal or Sal → Coc) while the other half remained in the same drug state (Coc → Coc or Sal → Sal). Results showed that male quail that were trained and tested in the same state (Coc → Coc or Sal → Sal) showed greater sexual conditioning than male quail that were trained and tested in different states (Sal → Coc) except when cocaine was administered chronically prior to the test (Coc → Sal). For the latter condition, sexual conditioning persisted from cocaine training to the saline test. The findings suggest that state dependent effects may alter sexual motivation and that repeated exposure to cocaine during sexual activity may increase sexual motivation which may, in turn, may lead to high risk sexual activities. An alternative explanation for the findings is also discussed. PMID:25447336

  3. Cocaine induces state-dependent learning of sexual conditioning in male Japanese quail.

    PubMed

    Gill, Karin E; Rice, Beth Ann; Akins, Chana K

    2015-01-01

    State dependent learning effects have been widely studied in a variety of drugs of abuse. However, they have yet to be studied in relation to sexual motivation. The current study investigated state-dependent learning effects of cocaine in male Japanese quail (Coturnix japonica) using a sexual conditioning paradigm. Cocaine-induced state-dependent learning effects were investigated using a 2×2 factorial design with training state as one factor and test state as the other factor. During a 14-day training phase, male quail were injected once daily with 10mg/kg cocaine or saline and then placed in a test chamber after 15min. In the test chamber, sexual conditioning trials consisted of presentation of a light conditioned stimulus (CS) followed by sexual reinforcement. During the state dependent test, half of the birds received a shift in drug state from training to testing (Coc→Sal or Sal→Coc) while the other half remained in the same drug state (Coc→Coc or Sal→Sal). Results showed that male quail that were trained and tested in the same state (Coc→Coc or Sal→Sal) showed greater sexual conditioning than male quail that were trained and tested in different states (Sal→Coc) except when cocaine was administered chronically prior to the test (Coc→Sal). For the latter condition, sexual conditioning persisted from cocaine training to the saline test. The findings suggest that state dependent effects may alter sexual motivation and that repeated exposure to cocaine during sexual activity may increase sexual motivation which, in turn, may lead to high risk sexual activities. An alternative explanation for the findings is also discussed. PMID:25447336

  4. Differential Antagonism of Cocaine Self-Administration and Cocaine-Induced Disruptions of Learning by Haloperidol in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Winsauer, Peter J.; Moerschbaecher, Joseph M.; Roussell, Alison M.

    2008-01-01

    Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032 - 0.032 mg/kg/infusion of cocaine increased response…

  5. Reduced Metabolsim in Brain 'Control Networks' Following Cocaine-Cues Exposure in Female Cocaine Abusers

    SciTech Connect

    Volkow, N.D.; Wang, G.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Telang, F.; Goldstein, R.Z.; Alia-Klein, N.; Wong, C.T.

    2011-03-01

    Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved. To test this we compared brain metabolism (using PET and {sup 18}FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video. Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (-8.6% {+-} 10) whereas males tended to increase it (+5.5% {+-} 18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus). Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from 'control networks' (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.

  6. Cocaine abuse in North America: a milestone in history.

    PubMed

    Das, G

    1993-04-01

    The euphoric effects of coca leaves have been known to mankind for thousands of years. Yet the first epidemic of cocaine use in America occurred during the late 19th century. Initially, there were no laws restricting the consumption or sale of cocaine. In fact, cocaine was freely available in drug stores, saloons, from mail-order vendors, and even in grocery stores. It is reported that one drug manufacturer, in 1885, was selling cocaine in 15 different forms, including cigarettes, cheroots, inhalants, cordials, crystals, and solutions. Many famous imported wines, such as "Vin Mariani," contained a mixture of wine and coca. For consumers on budgets, the wonder drug was available as Coca-Cola and dozens of other soda pops and pick-me-up drinks. One of them even had a simple and direct name, Dope. Soon enough, the ill effects of cocaine became apparent, and by the 1920s cocaine was the most feared of all illicit drugs. Most states began enacting laws against cocaine use. President William Taft proclaimed cocaine as Public Enemy No. 1, and in 1914 the Congress passed the Harrison act, which tightly regulated the distribution and sale of cocaine. By the late 1950s, cocaine use in the United States was simply considered a problem in the past. Unfortunately, the people who were aware of the nation's first cocaine epidemic gradually passed away, and America once again was ready for its fling with cocaine in the 1960s. Today, it is estimated that upwards of 50 million Americans, that is one in four, have used cocaine. In addition, another fifty thousand people use this substance for the first time each day. More than 6 million Americans use cocaine on a regular basis. Little wonder, then, that America as well as the other countries have declared a "War on Drugs." In this review, pharmacology of cocaine, major complications arising from its use, and efforts to curb its abuse are discussed. PMID:8473543

  7. Repeated Administration of a Mutant Cocaine Esterase: Effects on Plasma Cocaine Levels, Cocaine-Induced Cardiovascular Activity, and Immune Responses in Rhesus Monkeys

    PubMed Central

    Collins, Gregory T.; Brim, Remy L.; Noon, Kathleen R.; Narasimhan, Diwahar; Lukacs, Nicholas W.; Sunahara, Roger K.; Woods, James H.

    2012-01-01

    Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

  8. Repeated administration of a mutant cocaine esterase: effects on plasma cocaine levels, cocaine-induced cardiovascular activity, and immune responses in rhesus monkeys.

    PubMed

    Collins, Gregory T; Brim, Remy L; Noon, Kathleen R; Narasimhan, Diwahar; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2012-07-01

    Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

  9. Sensitive method for detection of cocaine and associated analytes by liquid chromatography-tandem mass spectrometry in urine.

    PubMed

    Langman, Loralie J; Bjergum, Matthew W; Williamson, Christopher L; Crow, Frank W

    2009-10-01

    Cocaine (COC) is a potent CNS stimulant that is metabolized to benzoylecgonine (BE) and further metabolized to minor metabolites such as m-hydroxybenzoylecgonine (m-HOBE). COC is also metabolized to norcocaine (NC). Cocaethylene (CE) is formed when cocaine and ethyl alcohol are used simultaneously. Anhydroecgonine methyl ester (AEME) is a unique marker following smoked cocaine, and anhydroecgonine ethyl ester (AEEE) is found in cocaine smokers who also use ethyl alcohol. We developed a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the detection and quantitation of COC, BE, NC, CE, m-HOBE, AEME, and AEEE in urine. Two hundred samples previously analyzed by gas chromatography (GC) coupled with MS were extracted using solid-phase extraction. Chromatographic separation was achieved using a gradient consisting of mobile phase A [20 mM ammonium formate (pH 2.7)] and mobile phase B (methanol/acetonitrile, 50:50), an XDB-C(8) (50 x 2.1 mm, 1.8 microm) column and a flow rate of 270 microL/min. Concentrations were calculated by comparing the peak-area with the internal standard and plotted against a standard curve. The assay displayed linearity from 1.0 to 100 ng/mL. Within- and between-run coefficients of variation were < 10% throughout the linear range. A method comparison between GC-MS and LC-MS-MS showed good correlation for COC (r(2) = 0.982) and BE (r(2) = 0.955). We report here on a sensitive method to identify clinically and forensically relevant cocaine and associated analytes at concentrations as low as 1.0 ng/mL. PMID:19874651

  10. Alcohol and Alcoholism.

    ERIC Educational Resources Information Center

    National Inst. of Mental Health (DHEW), Chevy Chase, MD. National Clearinghouse for Mental Health Information.

    This concise survey presents some of the highlights of modern research on drinking and alcoholism, as based on technical articles published in the scientific literature and the views expressed by leading authorities in the field. Contents include discussions about: (1) the nature and scope of the problem; (2) the chemical composition of alcoholic…

  11. Generalization of norcocaine to the discriminative stimulus properties of cocaine.

    PubMed

    Mckenna, M L; Ho, B T; Englert, L F

    1979-02-01

    In rats trained to discriminate 10 mg/kg cocaine from 1 mg/kg saline, norcocaine, the N-demethylated metabolite, at doses of 2.5 mg/kg, 5 mg/kg and 10 mg/kg, produced a dose response curve similar to that of cocaine and generalized to cocaine at the two higher doses. As with cocaine, the discriminative stimulus produced by the norcocaine was partially attenuated by the dopaminergic antagonist pimozide and the amine depletor reserpine. Benzoylecgonine, benzoylnorecgonine and ecgonine methyl ester in doses of 10 mg/kg and 20 mg/kg did not generalize to cocaine.

  12. Analysis of volatile organic compounds from illicit cocaine samples

    SciTech Connect

    Robins, W.H.; Wright, B.W.

    1994-07-01

    Detection of illicit cocaine hydrochloride shipments can be improved if there is a greater understanding of the identity and quantity of volatile compounds present. This study provides preliminary data concerning the volatile organic compounds detected in a limited Set of cocaine hydrochloride samples. In all cases, cocaine was one of the major volatile compounds detected. Other tropeines were detected in almost all samples. Low concentrations of compounds that may be residues of processing solvents were observed in some samples. The equilibrium emissivity of. cocaine from cocaine hydrochloride was investigated and a value of 83 parts-per-trillion was determined.

  13. Effects of chronic cocaine abuse on postsynaptic dopamine receptors

    SciTech Connect

    Volkow, N.D.; Fowler, J.S.; Wolf, A.P.; Schlyer, D.; Shiue, C.Y.; Alpert, R.; Dewey, S.L.; Logan, J.; Bendriem, B.; Christman, D. )

    1990-06-01

    To assess the effects of chronic cocaine intoxication on dopamine receptors in human subjects, the authors evaluated ({sup 18}F)N-methylspiroperidol binding using positron emission tomography in 10 cocaine abusers and 10 normal control subjects. Cocaine abusers who had been detoxified for 1 week or less showed significantly lower values for uptake of ({sup 18}F)N-methylspiroperidol in striatum than the normal subjects, whereas the cocaine abusers who had been detoxified for 1 month showed values comparable to those obtained from normal subjects. The authors conclude that postsynaptic dopamine receptor availability decreases with chronic cocaine abuse but may recover after a drug-free interval.

  14. Crack cocaine causing fatal vasoconstriction of the aorta.

    PubMed

    Williams, Joanne; Wasserberger, Jonathan

    2006-08-01

    Cocaine is the most powerful central nervous stimulant found in nature. All forms of cocaine cause tachycardia and vasoconstriction. A smokable, rapidly reacting form of cocaine base, "crack," is highly addictive. Smoking crack introduces a high concentration of cocaine into the bloodstream, rendering it especially dangerous. We report a case that visually demonstrates severe aortic vasoconstriction from the suprarenal aorta and extending to both femoral arteries and beyond, resulting in renal failure and fatal bowel ischemia after a 5-day binge of crack cocaine.

  15. Multicriteria wavenumber selection in cocaine classification.

    PubMed

    Anzanello, M J; Kahmann, A; Marcelo, M C A; Mariotti, K C; Ferrão, M F; Ortiz, R S

    2015-11-10

    Cocaine ATR-FTIR spectra consist of a large number of wavenumbers that typically decreases the performance of exploratory and predictive multivariate techniques. This paper proposes a framework for selecting the most relevant wavenumbers to classify cocaine samples into two categories regarding chemical composition, i.e. salt and base. The proposed framework builds a wavenumber importance index based on the Bhattacharyya distance (BD) followed by a procedure that removes wavenumbers from the spectra according to the order suggested by the BD index. The recommended wavenumber subset is chosen based on multiple criteria assessing classification performance, which are recalculated after each wavenumber is eliminated. The method was applied to ATR-FTIR spectra from 513 samples of cocaine, remarkably reducing the percent of retained wavenumbers and yielding near to perfect classifications in the testing set. In addition, we compared our propositions with other methods tailored to wavenumber selection; we found that the proposed framework, which relies on simple mathematical fundamentals, yielded competitive results.

  16. [Clinical concept of alcoholic dementia].

    PubMed

    Kato, N

    1991-06-01

    Intellectual deterioration, changing in behavior and affect are often seen in association with long continued and heavy alcohol ingestion and such deteriorated states of patients are called alcoholic dementia. A large number of investigators have attempted to designate clinical concept of alcoholic dementia throughout the centuries and many kinds of term like as alcoholic pseudo-paralysis, alcoholic mental deficiency and alcoholic deterioration, etc, have been submitted since the beginning of 19th century. Numerous psychometric studies have indicated cognitive impairment and memory disturbance in chronic alcohol abusers and moreover brain PEG and CT-scan studies have shown sulcal widening and enlarged ventricles to be common in alcoholics. However, alcoholic dementia is hard to classify as a distinct disorder caused by alcoholic ingestion. The reason is lack of specific findings, both clinical and histopathological, like as Wernicke-Korsakoff syndrome and other nutritional disorders in alcoholics. Victor, M. describes in his work the majority of patients who have come to autopsy with the clinical diagnosis of primary alcoholic dementia have shown the lesions of the Wernicke-Korsakoff syndrome and he postulates alcoholic dementia is heavily contaminated with burned-out Wernicke-Korsakoff disease. The clinical and pathological observations presented by this time represent alcoholic dementia is a residual category for cases in which there are severe impairment of intelligence with marked deterioration of personality following prolonged and heavy drinking.

  17. Dimensions of religion, depression symptomatology, and substance use among rural African American cocaine users.

    PubMed

    Montgomery, Brooke E E; Stewart, Katharine E; Bryant, Keneshia J; Ounpraseuth, Songthip T

    2014-01-01

    Research has shown a relationship between depression, substance use, and religiosity but, few have investigated this relationship in a community sample of African Americans who use drugs. This study examined the relationship between dimensions of religion (positive and negative religious coping; private and public religious participation; religious preference; and God-, clergy-, and congregation-based religious support), depression symptomatology, and substance use among 223 African American cocaine users. After controlling for gender, employment, and age, greater congregation-based support and greater clergy-based support were associated with fewer reported depressive symptoms. In addition, greater congregation-based support was associated with less alcohol use. PMID:24564561

  18. Causal Pathways Between Impulsiveness, Cocaine Use Consequences, and Depression

    PubMed Central

    Lister, Jamey J.; Ledgerwood, David M.; Lundahl, Leslie H.; Greenwald, Mark K.

    2014-01-01

    Aims The present study examined whether lifetime cocaine use consequences mediate the relationship between trait impulsiveness and current depression symptoms among regular cocaine users. Methods Regular cocaine users (N = 108) were assessed using: Barratt Impulsiveness Scale subscales (non-planning, attentional, motor sub-scales) to measure trait impulsiveness; a standardized Drug History and Use Questionnaire to measure cocaine use and related consequences; and Beck Depression Inventory to measure current depression symptoms. Results All impulsiveness subscales were positively associated with an earlier age of first cocaine use, a higher degree of current depression symptoms and a greater number of lifetime cocaine use consequences. In three separate simple mediation tests, lifetime cocaine use consequences partially mediated the relationship between each of the impulsiveness subscales (non-planning: R2 = .42; attentional: R2 = .40; motor: R2 = .24) and current depression symptoms. Separate moderated mediation analyses failed to demonstrate an interaction between lifetime cocaine use and cocaine-related consequences predicting depression symptoms for the mediation models. Conclusions Cocaine-related consequences function in a more nuanced manner than just an outcome of impulsiveness or cocaine use, but as a pathway between trait impulsiveness and current depression symptoms. PMID:25280245

  19. Decreased brain dopamine cell numbers in human cocaine users.

    PubMed

    Little, Karley Y; Ramssen, Eric; Welchko, Ryan; Volberg, Vitaly; Roland, Courtney J; Cassin, Bader

    2009-08-15

    Cocaine use diminishes striatal and midbrain dopamine neuronal components in both post-mortem and in vivo human experiments. The diffuse nature of these declines suggests the possibility that cocaine use might cause a loss of dopamine neurons in humans. Previous rodent studies have not detected cocaine-induced dopamine cell damage. The present experiment involved counting midbrain dopamine neurons utilizing both melanin and tyrosine hydroxylase immunoreactivity. Well-preserved blocks ranging from +38 mm obex to +45 mm obex were examined in 10 cocaine users and 9 controls. Sections were also examined for signs of acute pathological injury by counting activated macrophages and microglia. Melanized cells at six midbrain levels were significantly reduced in cocaine users by both drug exposures. The estimated total number of melanized dopamine cells in the anterior midbrain was significantly reduced in cocaine users by 16%. Results with tyrosine hydroxylase immunoreactivity were less conclusive because of variability in staining. Both activated macrophages and activated microglia were significantly increased among cocaine users. Cocaine exposure may have neurotoxic effects on dopamine neurons in humans. The infiltration of phagocytic cells suggests that the lower number of dopamine cells found in cocaine users was a relatively recent effect. The loss of dopamine cells could contribute to and intensify cocaine dependence, as well as anhedonic and depressive symptoms, in some cocaine users. Further efforts at clarifying the pathophysiological mechanisms involved may help explain treatment refractoriness, and identify targets for therapeutic intervention. PMID:19233481

  20. Effects of mazindol on behavior maintained or occasioned by cocaine.

    PubMed

    Mansbach, R S; Balster, R L

    1993-01-01

    The effects of mazindol, cocaine and D-amphetamine were studied in rhesus monkeys trained to self-administer cocaine, and in rats and squirrel monkeys trained to discriminate cocaine from saline. Non-contingent intravenous drug injections were administered to monkeys responding under a session consisting of a 5-min period during which lever-pressing produced food reinforcement and a 60-min session in which responding produced i.v. cocaine infusions (10 or 33 micrograms/kg per infusion). Acute i.v. injections of cocaine (0.1-1.7 mg/kg), D-amphetamine (0.1-1 mg/kg) and the dopamine re-uptake inhibitor mazindol (0.03-0.56 mg/kg) given 5 min before the session decreased self-administration of cocaine, but also decreased rates of behavior maintained by the presentation of food. In both rats and squirrel monkeys trained to discriminate cocaine from saline in a two-lever, food-maintained procedure, mazindol, cocaine and D-amphetamine substituted for cocaine in a dose-related manner. Despite a lack of selectivity to decrease cocaine self-administration as compared to behavior maintained by food, the present data provide some rationale for further consideration of mazindol as a potential pharmacotherapy for stimulant abuse, due to its relatively low abuse liability and cocaine-like discriminative stimulus effects. PMID:8436063

  1. Demonstration of specific binding of cocaine to human spermatozoa

    SciTech Connect

    Yazigi, R.A.; Odem, R.R.; Polakoski, K.L. )

    1991-10-09

    Exposure of males to cocaine has been linked to abnormal development of their offspring. To investigate the possible role of sperm, this study examined the interaction of cocaine with human spermatozoa. Washed sperm were incubated with tritiated cocaine and the samples were filtered and the remaining radioactivity quantitated. The specific binding was optimal at 20 minutes and 23C. Competition studies with tritiated cocaine indicated the presence of approximately 3.6 {times} 10{sup 3} binding sites per cell, with a high affinity receptor dissociation constant. Cocaine concentrations as high as 670 {mu}mol/L had no detectable effect on either the motility or viability of the cells. These results support the hypothesis that the sperm may act as a vector to transport cocaine into an ovum. This novel mechanism could be involved in the abnormal development of offspring of cocaine-exposed males.

  2. Malignant hypertension-associated thrombotic microangiopathy following cocaine use.

    PubMed

    Lamia, Rais; El Ati, Zohra; Ben Fatma, Lilia; Zouaghi, Karim; Smaoui, Wided; Rania, Khedher; Krid, Madiha; Ben Hmida, Fathi; Béji, Soumaya; Ben Moussa, Fatma

    2016-01-01

    Cocaine is one of the most commonly used illicit drugs with distribution and consumption throughout the world. Acute renal failure associated with rhabdomyolysis, direct vasoconstriction and hemodynamic alteration is well described in patients with cocaine intoxication. Cocaine use is associated with high blood pressure and may rarely induce malignant hypertension associated with thrombotic microangiopathy. We report the case of a patient who developed malignant hypertension associated with thrombotic microangiopathy after chronic consumption of cocaine. A kidney biopsy revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. He required dialysis sessions. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop malignant hypertension associated with thrombotic microangiopathy. Clinicians need to be aware of this rare feature of cocaine intoxication. PMID:26787585

  3. Polyvinyl alcohol nanofiber formulation of the designer antimicrobial peptide APO sterilizes Acinetobacter baumannii-infected skin wounds in mice.

    PubMed

    Sebe, Istvan; Ostorhazi, Eszter; Fekete, Aron; Kovacs, Krisztian N; Zelko, Romana; Kovalszky, Ilona; Li, Wenyi; Wade, John D; Szabo, Dora; Otvos, Laszlo

    2016-01-01

    Native and designer cationic antimicrobial peptides are increasingly acknowledged as host defense molecules rather than true antimicrobials. Due to their ability to activate the innate immune system, these structures are used to treat uninfected and bacterially-infected wounds, including those harboring Acinetobacter baumannii. Previously we documented that when administered intramuscularly or topically in liquid formulations, the proline-rich host defense peptide dimer A3-APO accelerates uninfected wound re-epithelization and eliminates systemic and local A. baumannii, methicillin-resistant Staphylococcus aureus and other pathogen load from infected lesions better than conventional antibiotics. In the current study we sought to produce and characterize a novel delivery system, suitable for immediate and convenient application in non-hospital environments. The APO monomer was incorporated into polyvinyl alcohol nanofibers and the complex was polymerized into a solid patch dressing. Mice were subjected to skin abrasion where the wounds were either left uninfected or were inoculated with a near lethal dose of multidrug resistant A. baumannii strain. Analyzed after 3 days, APO monomer-containing patches improved wound appearance significantly better than polymer patches without antibiotics. When compared to colistin, the APO patches accelerated wound healing, and statistically significantly reduced wound size and wound bacterial load. The in vivo antimicrobial effect was more extensive than after intramuscular administration of the peptide drug, by using only one tenth of the active pharmaceutical ingredient. These data suggest that the APO monomer-impregnated nanofiber dressing can be developed as an economical first-line treatment option to skin injuries in general and battlefield burn and blast injuries in particular. PMID:26319645

  4. Broadening the cofactor specificity of a thermostable alcohol dehydrogenase using rational protein design introduces novel kinetic transient behavior.

    PubMed

    Campbell, Elliot; Wheeldon, Ian R; Banta, Scott

    2010-12-01

    Cofactor specificity in the aldo-keto reductase (AKR) superfamily has been well studied, and several groups have reported the rational alteration of cofactor specificity in these enzymes. Although most efforts have focused on mesostable AKRs, several putative AKRs have recently been identified from hyperthermophiles. The few that have been characterized exhibit a strong preference for NAD(H) as a cofactor, in contrast to the NADP(H) preference of the mesophilic AKRs. Using the design rules elucidated from mesostable AKRs, we introduced two site-directed mutations in the cofactor binding pocket to investigate cofactor specificity in a thermostable AKR, AdhD, which is an alcohol dehydrogenase from Pyrococcus furiosus. The resulting double mutant exhibited significantly improved activity and broadened cofactor specificity as compared to the wild-type. Results of previous pre-steady-state kinetic experiments suggest that the high affinity of the mesostable AKRs for NADP(H) stems from a conformational change upon cofactor binding which is mediated by interactions between a canonical arginine and the 2'-phosphate of the cofactor. Pre-steady-state kinetics with AdhD and the new mutants show a rich conformational behavior that is independent of the canonical arginine or the 2'-phosphate. Additionally, experiments with the highly active double mutant using NADPH as a cofactor demonstrate an unprecedented transient behavior where the binding mechanism appears to be dependent on cofactor concentration. These results suggest that the structural features involved in cofactor specificity in the AKRs are conserved within the superfamily, but the dynamic interactions of the enzyme with cofactors are unexpectedly complex.

  5. Optimal design and characterization of superparamagnetic iron oxide nanoparticles coated with polyvinyl alcohol for targeted delivery and imaging.

    PubMed

    Mahmoudi, Morteza; Simchi, Abdolreza; Imani, Mohammad; Milani, Abbas S; Stroeve, Pieter

    2008-11-20

    Superparamagnetic iron oxide nanoparticles (SPION) with narrow size distribution and stabilized by polyvinyl alcohol (PVA) were synthesized. The particles were prepared by a coprecipitation technique using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Using a design of experiments (DOE) approach, the effect of different synthesis parameters (stirring rate and base molarity) on the structure, morphology, saturation magnetization, purity, size, and size distribution of the synthesized magnetite nanoparticles was studied by various analysis techniques including X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) with differential scanning calorimetry (DSC) measurements, vibrating-sample magnetometer (VSM), transmission electron microscopy (TEM), UV-visible, and Fourier transform infrared (FT-IR) spectrometer. PVA not only stabilized the colloid but also played a role in preventing further growth of SPION followed by the formation of large agglomerates by chemisorption on the surface of particles. A rich behavior in particle size, particle formation, and super paramagnetic properties is observed as a function of molarity and stirring conditions. The particle size and the magnetic properties as well as particle shape and aggregation (individual nanoparticles, magnetic beads, and magnetite colloidal nanocrystal clusters (CNCs) are found to be influenced by changes in the stirring rate and the base molarity. The formation of magnetic beads results in a decrease in the saturation magnetization, while CNCs lead to an increase in saturation magnetization. On the basis of the DOE methodology and the resulting 3-D response surfaces for particle size and magnetic properties, it is shown that optimum regions for stirring rate and molarity can be obtained to achieve coated SPION with desirable size, purity, magnetization, and shape.

  6. Omega-3 fatty acids for treatment of non-alcoholic fatty liver disease: design and rationale of randomized controlled trial

    PubMed Central

    2013-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome since obesity and insulin resistance are the main pathogenic contributors for both conditions. NAFLD carries increased risk of atherosclerosis and cardiovascular diseases. There is an urgent need to find effective and safe therapy for children and adults with NAFLD. Data from research and clinical studies suggest that omega-3 fatty acids may be beneficial in metabolic syndrome-related conditions and can reduce the risk of cardiovascular disease. Methods/design We are conducting a randomized, multicenter, double-blind, placebo-controlled trial of treatment with omega-3 fatty acids in children with NAFLD. Patients are randomized to receive either omega-3 fatty acids containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or placebo for 24 weeks. The dose of omega-3 (DHA+ EPA) ranges from 450 to 1300 mg daily. Low calorie diet and increased physical activity are advised and monitored using validated questionnaires. The primary outcome of the trial is the number of patients who decreased ALT activity by ≥ 0,3 of upper limit of normal. The main secondary outcomes are improvement in the laboratory liver tests, liver steatosis on ultrasound, markers of insulin resistance and difference in fat/lean body mass composition after 6 months of intervention. Discussion Potential efficacy of omega-3 fatty acids in the treatment of NAFLD will provide needed rationale for use of this safe diet supplement together with weight reduction therapy in the growing population of children with NAFLD. Trial registration NCT01547910 PMID:23702094

  7. Polyvinyl alcohol nanofiber formulation of the designer antimicrobial peptide APO sterilizes Acinetobacter baumannii-infected skin wounds in mice.

    PubMed

    Sebe, Istvan; Ostorhazi, Eszter; Fekete, Aron; Kovacs, Krisztian N; Zelko, Romana; Kovalszky, Ilona; Li, Wenyi; Wade, John D; Szabo, Dora; Otvos, Laszlo

    2016-01-01

    Native and designer cationic antimicrobial peptides are increasingly acknowledged as host defense molecules rather than true antimicrobials. Due to their ability to activate the innate immune system, these structures are used to treat uninfected and bacterially-infected wounds, including those harboring Acinetobacter baumannii. Previously we documented that when administered intramuscularly or topically in liquid formulations, the proline-rich host defense peptide dimer A3-APO accelerates uninfected wound re-epithelization and eliminates systemic and local A. baumannii, methicillin-resistant Staphylococcus aureus and other pathogen load from infected lesions better than conventional antibiotics. In the current study we sought to produce and characterize a novel delivery system, suitable for immediate and convenient application in non-hospital environments. The APO monomer was incorporated into polyvinyl alcohol nanofibers and the complex was polymerized into a solid patch dressing. Mice were subjected to skin abrasion where the wounds were either left uninfected or were inoculated with a near lethal dose of multidrug resistant A. baumannii strain. Analyzed after 3 days, APO monomer-containing patches improved wound appearance significantly better than polymer patches without antibiotics. When compared to colistin, the APO patches accelerated wound healing, and statistically significantly reduced wound size and wound bacterial load. The in vivo antimicrobial effect was more extensive than after intramuscular administration of the peptide drug, by using only one tenth of the active pharmaceutical ingredient. These data suggest that the APO monomer-impregnated nanofiber dressing can be developed as an economical first-line treatment option to skin injuries in general and battlefield burn and blast injuries in particular.

  8. Cocaine and metabolite concentrations in DBS and venous blood after controlled intravenous cocaine administration

    PubMed Central

    Ellefsen, Kayla N; da Costa, Jose Luiz; Concheiro, Marta; Anizan, Sebastien; Barnes, Allan J; Pirard, Sandrine; Gorelick, David A; Huestis, Marilyn A

    2015-01-01

    Background: DBS are an increasingly common clinical matrix. Methods & results: Sensitive and specific methods for DBS and venous blood cocaine and metabolite detection by LC–HRMS and 2D GC–MS, respectively, were validated to examine correlation between concentrations following controlled intravenous cocaine administration. Linear ranges from 1 to 200 µg/l were achieved, with acceptable bias and imprecision. Authentic matched specimens’ (392 DBS, 97 venous blood) cocaine and benzoylecgonine concentrations were qualitatively similar, but DBS had much greater variability (21.4–105.9 %CV) and were lower than in blood. Conclusion: DBS offer advantages for monitoring cocaine intake; however, differences between capillary and venous blood and DBS concentration variability must be addressed. PMID:26327184

  9. Alcohol use disorder

    MedlinePlus

    ... Alcohol abuse; Problem drinking; Drinking problem; Alcohol addiction; Alcoholism - alcohol use; Substance use - alcohol ... The National Institute on Alcohol Abuse and Alcoholism ... 1 drink per day Men should not drink more than 2 drinks per day

  10. AAVrh.10-Mediated Expression of an Anti-Cocaine Antibody Mediates Persistent Passive Immunization That Suppresses Cocaine-Induced Behavior

    PubMed Central

    Rosenberg, Jonathan B.; Hicks, Martin J.; De, Bishnu P.; Pagovich, Odelya; Frenk, Esther; Janda, Kim D.; Wee, Sunmee; Koob, George F.; Hackett, Neil R.; Kaminsky, Stephen M.; Worgall, Stefan; Tignor, Nicole; Mezey, Jason G.

    2012-01-01

    Abstract Cocaine addiction is a major problem affecting all societal and economic classes for which there is no effective therapy. We hypothesized an effective anti-cocaine vaccine could be developed by using an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain. To accomplish this, we constructed AAVrh.10antiCoc.Mab, an AAVrh.10 gene transfer vector expressing the heavy and light chains of the high affinity anti-cocaine monoclonal antibody GNC92H2. Intravenous administration of AAVrh.10antiCoc.Mab to mice mediated high, persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood. With repeated intravenous cocaine challenge, naive mice exhibited hyperactivity, while the AAVrh.10antiCoc.Mab-vaccinated mice were completely resistant to the cocaine. These observations demonstrate a novel strategy for cocaine addiction by requiring only a single administration of an AAV vector mediating persistent, systemic anti-cocaine passive immunity. PMID:22486244

  11. Safety of Atomoxetine in Combination with Intravenous Cocaine in Cocaine- Experienced Participants

    PubMed Central

    Cantilena, Louis; Kahn, Roberta; Duncan, Connie C.; Li, Shou-Hua; Anderson, Ann; Elkashef, Ahmed

    2012-01-01

    Objectives Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine, and also whether cognitive function was affected by atomoxetine during short-term administration. Methods In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 mg and 40 mg) was infused intravenously in sequential daily sessions. Results Pre-infusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Pre-infusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80 mg and 100 mg atomoxetine doses. All ECG parameters were unchanged. VAS scores for “bad effect” in the atomoxetine group were significantly higher at baseline, then declined, and for “likely to use” declined with atomoxetine treatment. On the ARCI the atomoxetine group scored significantly lower on amphetamine, euphoria and energy subscales (p<0.0001). Other VAS descriptors, BSCS, POMS, and BPRS showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. Conclusions Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine. PMID:22987022

  12. Atomoxetine Does Not Alter Cocaine Use in Cocaine Dependent Individuals: A Double Blind Randomized Trial

    PubMed Central

    Middleton, Lisa S.; Wong, Conrad J.; Nuzzo, Paul A.; Campbell, Charles L.; Rush, Craig R.; Lofwall, Michelle R.

    2016-01-01

    Background Cocaine abuse continues to be a significant public health problem associated with morbidity and mortality. To date, no pharmacotherapeutic approach has proven effective for treating cocaine use disorders. Preclinical and clinical evidence suggests that noradrenergic activity may play a role in mediating some effects of cocaine and may be a rational target for treatment. Methods This double blind, placebo-controlled randomized, parallel group, 12-week outpatient clinical trial enrolled cocaine dependent individuals seeking treatment to examine the potential efficacy of the selective norepinephrine reuptake inhibitor, atomoxetine (80 mg/day; p.o.; n=25), compared to placebo (n=25). Subjects were initially stratified on cocaine use (<15 days or ≥15 days of the last 30), age and race using urn randomization. Attendance, medication adherence and study compliance were reinforced with contingency management, and weekly counseling was offered. An array of measures (vital signs, laboratory chemistries, cognitive and psychomotor tests, cocaine craving and urine samples for drug testing) was collected throughout the study and at follow-up. Results Survival analysis revealed no differences in study retention between the two groups, with approximately 56% of subjects completing the 12-week study (Cox analysis X2=.72; p=.40; Hazard Ratio 1.48 [CI 0.62–3.39]). GEE analysis of the proportion of urine samples positive for benzoylecgonine, a cocaine metabolite, revealed no differences between the atomoxetine and placebo groups (X2=0.2, p=.66; OR=0.89 [95% CI 0.41 – 1.74). Atomoxetine was generally well tolerated in this population. Conclusions These data provide no support for the utility of atomoxetine in the treatment of cocaine dependence. PMID:23200303

  13. Recent Advances in Nicotinic Receptor Signaling in Alcohol Abuse and Alcoholism.

    PubMed

    Rahman, Shafiqur; Engleman, Eric A; Bell, Richard L

    2016-01-01

    Alcohol is the most commonly abused legal substance and alcoholism is a serious public health problem. It is a leading cause of preventable death in the world. The cellular and molecular mechanisms of alcohol reward and addiction are still not well understood. Emerging evidence indicates that unlike other drugs of abuse, such as nicotine, cocaine, or opioids, alcohol targets numerous channel proteins, receptor molecules, and signaling pathways in the brain. Previously, research has identified brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of pentameric ligand-gated cation channels expressed in the mammalian brain, as critical molecular targets for alcohol abuse and dependence. Genetic variations encoding nAChR subunits have been shown to increase the vulnerability to develop alcohol dependence. Here, we review recent insights into the rewarding effects of alcohol, as they pertain to different nAChR subtypes, associated signaling molecules, and pathways that contribute to the molecular mechanisms of alcoholism and/or comorbid brain disorders. Understanding these cellular changes and molecular underpinnings may be useful for the advancement of brain nicotinic-cholinergic mechanisms, and will lead to a better translational and therapeutic outcome for alcoholism and/or comorbid conditions.

  14. Identification of Behavior Change Techniques and Engagement Strategies to Design a Smartphone App to Reduce Alcohol Consumption Using a Formal Consensus Method

    PubMed Central

    Crane, David; West, Robert; Brown, Jamie; Michie, Susan

    2015-01-01

    engagement strategies (W=.563, χ2 15=59.2, P<.001) and those with the highest mean rankings were ease of use, design – aesthetic, feedback, function, design – ability to change design to suit own preferences, tailored information, and unique smartphone features. Conclusions The BCTs with greatest potential to include in a smartphone app to reduce alcohol consumption were judged by experts to be self-monitoring, goal-setting, action planning, and feedback in relation to goals. The strategies most likely to engage users were ease of use, design, tailoring of design and information, and unique smartphone features. PMID:26123578

  15. The 5-HT(2C) receptor agonist lorcaserin reduces cocaine self-administration, reinstatement of cocaine-seeking and cocaine induced locomotor activity.

    PubMed

    Harvey-Lewis, Colin; Li, Zhaoxia; Higgins, Guy A; Fletcher, Paul J

    2016-02-01

    Lorcaserin (Lorqess, Belviq(®)) is a selective 5-HT(2C) receptor agonist that has received FDA approval for the treatment of obesity. 5-HT(2C) receptor agonists are also efficacious in decreasing multiple aspects of cocaine motivation and reward in preclinical models. This would suggest that lorcaserin is a clinically available therapeutic with the potential to treat cocaine addiction. Here we report the effects of lorcaserin (0.1 mg/kg-1.0 mg/kg) on multiple aspects of cocaine-related behaviours in rats. We find that lorcaserin dose-dependently decreases cocaine self-administration on progressive and fixed ratio schedules of reinforcement. Lorcaserin also reduces reinstatement of cocaine-seeking behaviour in response to priming injections of cocaine and/or reintroduction of cocaine-associated cues. Finally, lorcaserin dose-dependently decreases cocaine-induced hyperlocomotion. Our results, when considered in concert with similar emergent findings in non-human primates, strongly support continued research into the potential of lorcaserin as a clinical treatment for cocaine addiction.

  16. Oxytocin Reduces Cocaine Seeking and Reverses Chronic Cocaine-Induced Changes in Glutamate Receptor Function

    PubMed Central

    Zhou, Luyi; Sun, Wei-Lun; Young, Amy B.; Lee, Kunhee; McGinty, Jacqueline F.

    2015-01-01

    Background: Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. Methods: In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Results: Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. Conclusions: These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. PMID:25539504

  17. Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction

    PubMed Central

    Narasimhan, Diwahar; Woods, James H; Sunahara, Roger K

    2012-01-01

    Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine’s pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37°C, thus limiting CocE’s potential. Innovative computational methods based on the protein’s structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction. PMID:22300094

  18. The skinny on cocaine: insights into eating behavior and body weight in cocaine-dependent men.

    PubMed

    Ersche, Karen D; Stochl, Jan; Woodward, Jeremy M; Fletcher, Paul C

    2013-12-01

    There is a general assumption that weight loss associated with cocaine use reflects its appetite suppressing properties. We sought to determine whether this was justified by characterizing, in detail, alterations in dietary food intake and body composition in actively using cocaine-dependent individuals. We conducted a cross-sectional case-control comparison of 65 male volunteers from the local community, half of whom satisfied the DSM-IV-TR criteria for cocaine dependence (n=35) while the other half had no personal or family history of a psychiatric disorder, including substance abuse (n=30). Assessments were made of eating behavior and dietary food intake, estimation of body composition, and measurement of plasma leptin. Although cocaine users reported significantly higher levels of dietary fat and carbohydrates as well as patterns of uncontrolled eating, their fat mass was significantly reduced compared with their non-drug using peers. Levels of leptin were associated with fat mass, and with the duration of stimulant use. Tobacco smoking status or concomitant use of medication did not affect the significance of the results. Weight changes in cocaine users reflect fundamental perturbations in fat regulation. These are likely to be overlooked in clinical practice but may produce significant health problems when cocaine use is discontinued during recovery.

  19. Daily stressor sensitivity, abuse effects, and cocaine use in cocaine dependence.

    PubMed

    Waldrop, Angela E; Back, Sudie E; Brady, Kathleen T; Upadhyaya, Himanshu P; McRae, Aimee L; Saladin, Michael E

    2007-12-01

    This study highlights respondent sensitivity to daily hassles as it relates to situational cocaine use and perceived long-term effects of adverse events in childhood. Data were drawn from a larger study on stress reactivity in cocaine dependent individuals. Participants (n=104) were cocaine dependent men and women without comorbid posttraumatic stress disorder (PTSD). They completed the Early Trauma Inventory (ETI), the Daily Hassles Scale (DHS), the Inventory of Drug-Taking Situations (IDTS), and the Time-Line Follow-Back (TLFB; for 90 days prior to interview). There were no gender differences in the amount or frequency of cocaine use, although the patterns of use differed between male and female users. Overall, there were some associations in the patterns of cocaine use and sensitivity to daily hassles, particularly the use in response to conflict with others. Early negative life events were positively related to response to daily hassles, but current triggers were more relevant. Reactivity to cocaine cues was related to daily hassle sensitivity among women only. Limitations and implications of the findings are discussed.

  20. Race/Ethnic-Specific Homicide Rates in New York City: Evaluating the Impact of Broken Windows Policing and Crack Cocaine Markets

    PubMed Central

    Chauhan, Preeti; Cerdá, Magdalena; Messner, Steven F.; Tracy, Melissa; Tardiff, Kenneth; Galea, Sandro

    2012-01-01

    The current study evaluated a range of social influences including misdemeanor arrests, drug arrests, cocaine consumption, alcohol consumption, firearm availability, and incarceration that may be associated with changes in gun-related homicides by racial/ethnic group in New York City (NYC) from 1990 to 1999. Using police precincts as the unit of analysis, we used cross-sectional, time series data to examine changes in Black, White, and Hispanic homicides, separately. Bayesian hierarchical models with a spatial error term indicated that an increase in cocaine consumption was associated with an increase in Black homicides. An increase in firearm availability was associated with an increase in Hispanic homicides. Last, there were no significant predictors for White homicides. Support was found for the crack cocaine hypotheses but not for the broken windows hypothesis. Examining racially/ethnically disaggregated data can shed light on group-sensitive mechanisms that may explain changes in homicide over time. PMID:22328820

  1. Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys

    PubMed Central

    Schindler, Charles W.; Justinova, Zuzana; Lafleur, David; Woods, Doug; Roschke, Viktor; Hallak, Hussein; Sklair-Tavron, Liora; Redhi, Godfrey H.; Yasar, Sevil; Bergman, Jack; Goldberg, Steven R.

    2011-01-01

    Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu-CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000-fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced two hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hrs following Albu-CocH administration. In behavioral experiments in monkeys, pretreatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 μg/kg/injection) for over 24 hours. Pretreatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted. PMID:22264200

  2. A recombinant humanized anti-cocaine monoclonal antibody inhibits the distribution of cocaine to the brain in rats.

    PubMed

    Norman, Andrew B; Gooden, Felicia C T; Tabet, Michael R; Ball, William J

    2014-07-01

    The monoclonal antibody (mAb), h2E2, is a humanized version of the chimeric human/murine anti-cocaine mAb 2E2. The recombinant h2E2 protein was produced in vitro from a transfected mammalian cell line and retained high affinity (4 nM Kd) and specificity for cocaine over its inactive metabolites benzoylecgonine (BE) and ecgonine methyl ester. In rats, pharmacokinetic studies of h2E2 (120 mg/kg i.v.) showed a long terminal elimination half-life of 9.0 days and a low volume of distribution at steady state (Vdss) of 0.3 l/kg. Pretreatment with h2E2 produced a dramatic 8.8-fold increase in the area under the plasma cocaine concentration-time curve (AUC) and in brain a concomitant decrease of 68% of cocaine's AUC following an i.v. injection of an equimolar cocaine dose. Sequestration of cocaine in plasma by h2E2, shown via reduction of cocaine's Vdss, indicates potential clinical efficacy. Although the binding of cocaine to h2E2 in plasma should inhibit distribution and metabolism, the elimination of cocaine remained multicompartmental and was still rapidly eliminated from plasma despite the presence of h2E2. BE was the major cocaine metabolite, and brain BE concentrations were sixfold higher than in plasma, indicating that cocaine is normally metabolized in the brain. In the presence of h2E2, brain BE concentrations were decreased and plasma BE was increased, consistent with the observed h2E2-induced changes in cocaine disposition. The inhibition of cocaine distribution to the brain confirms the humanized mAb, h2E2, as a lead candidate for development as an immunotherapy for cocaine abuse. PMID:24733787

  3. Late Dose-Response Effects of Prenatal Cocaine Exposure on Newborn Neurobehavioral Performance

    PubMed Central

    Tronick, Edward Z.; Frank, Deborah A.; Cabral, Howard; Mirochnick, Mark; Zuckerman, Barry

    2008-01-01

    Objective To determine in a representative sample of full-term urban newborns of English-speaking mothers whether an immediate or late dose-response effect could be demonstrated between prenatal cocaine exposure and newborn neurobehavioral performance, controlling for confounding factors. Methods The Neonatal Behavioral Assessment Scale (NBAS) was administered by masked examiners to a total sample of 251 clinically healthy, full-term infants at 2 days and/or 17 days. Three in utero cocaine exposure groups were defined: heavily exposed (n = 44, >75th percentile self-reported days of use during pregnancy and/or >75th percentile of meconium benzoylecognine concentration); lightly exposed (n = 79, less than both 75th percentiles); and unexposed (n = 101, no positive biological or self-report marker). At the 3-week examination there were 38 heavily exposed, 73 lightly exposed, and 94 unexposed infants. Controlling for infant birth weight, gestational age, infant age at the time of examination, mothers’ age, perinatal risk, obstetric medication, and alcohol, marijuana, and cigarette use, a regression analysis evaluated the effects of levels of cocaine exposure on NBAS performance. Results No neurobehavioral effects of exposure on the newborn NBAS cluster scores or on the qualifier scores were found when confounders were controlled for at 2 to 3 days of age. At 3 weeks, after controlling for covariates, a significant dose effect was observed, with heavily exposed infants showing poorer state regulation and greater excitability. Conclusions These findings demonstrate specific dose-related effects of cocaine on 3-week neurobehavioral performance, particularly for the regulation of arousal, which was not observed in the first few days of life. PMID:8668416

  4. Overlapping Dopaminergic Pathway Genetic Susceptibility for Heroin and Cocaine Addictions in African Americans

    PubMed Central

    Levran, Orna; Randesi, Matthew; da Rosa, Joel Correa; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

    2015-01-01

    Summary Drugs of abuse activate the mesolimbic dopaminergic pathway. Genetic variations in the dopaminergic system may contribute to vulnerability to drug addiction. Several processes are shared between cocaine and heroin addictions but some neurobiological mechanisms and environmental influence may be specific. This study examined the association of 98 single nucleotide polymorphisms (SNPs) in 13 dopamine pathway-related genes with heroin and/or cocaine addiction in a sample of 801 African Americans (315 subjects with heroin addiction (OD), with or without cocaine (CD) or alcohol addiction (AD), 279 subjects with CD, with or without AD, and 207 controls). Single-marker analyses provided nominally significant evidence for associations of 24 SNPs in DRD1, ANKK1/DRD2, DRD3, DRD5, DBH, DDC, COMT and CSNK1E with OD and/or CD. A DRD2 7-SNPs haplotype block that includes SNPs rs1075650 and rs2283265, which were shown to alter D2S/D2L splicing, was indicated in both addictions. The Met allele of the COMT Val158Met functional variant was associated with protection from OD. None of the signals remained significant after correction for multiple testing. The study results are in accordance with the results of several previous studies, including our report of association of DRD1 SNP rs5326 with OD in a smaller sample from this cohort. The findings suggest the presence of an overlap in the genetic liability for heroin and cocaine addictions, as well as shared and distinct liability for OD in subjects of African and European descent. PMID:25875614

  5. Dopamine Transporter Correlates and Occupancy by Modafinil in Cocaine-Dependent Patients: A Controlled Study With High-Resolution PET and [(11)C]-PE2I.

    PubMed

    Karila, Laurent; Leroy, Claire; Dubol, Manon; Trichard, Christian; Mabondo, Audrey; Marill, Catherine; Dubois, Albertine; Bordas, Nadège; Martinot, Jean-Luc; Reynaud, Michel; Artiges, Eric

    2016-08-01

    Modafinil is a candidate compound for the treatment of cocaine addiction that binds to the dopamine transporter (DAT) in healthy humans, as observed by positron emission tomography (PET). This mechanism, analogous to that of cocaine, might mediate a putative therapeutic effect of modafinil on cocaine dependence, though the binding of modafinil to DAT has never been assessed in cocaine-dependent patients. We aimed at quantifying the DAT availability during a controlled treatment by modafinil, and its clinical and psychometric correlates in cocaine-dependent patients at the onset of abstinence initiation. Twenty-nine cocaine-dependent male patients were enrolled in a 3-month trial for cocaine abstinence. Modafinil was used in a randomized double-blind placebo-controlled design and was administered as follows: 400 mg/day for 26 days, then 300 mg/day for 30 days, and 200 mg/day for 31 days. Participants were examined twice during a 17-day hospitalization for their DAT availability using PET and [(11)C]-PE2I and for assessments of craving, depressive symptoms, working memory, and decision-making. Cocaine abstinence was further assessed during a 10-week outpatient follow-up period. Baseline [(11)C]-PE2I-binding potential covaried with risk taking and craving index in striatal and extrastriatal regions. A 65.6% decrease of binding potential was detected in patients receiving modafinil for 2 weeks, whereas placebo induced no significant change. During hospitalization, an equivalent improvement in clinical outcomes was observed in both treatment groups, and during the outpatient follow-up there were more therapeutic failures in the modafinil-treated group. Therefore, these results do not support the usefulness of modafinil to treat cocaine addiction. PMID:26892922

  6. Case Study: The Chemistry of Cocaine

    ERIC Educational Resources Information Center

    Dewprashad, Brahmadeo

    2011-01-01

    This column provides original articles on innovations in case study teaching, assessment of the method, as well as case studies with teaching notes. This month's case study focuses on the chemistry of cocaine to teach a number of core concepts in organic chemistry. It also requires that students read and analyze an original research paper on…

  7. Cocaine-induced pulmonary changes: HRCT findings *

    PubMed Central

    de Almeida, Renata Rocha; Zanetti, Gláucia; Souza, Arthur Soares; de Souza, Luciana Soares; Silva, Jorge Luiz Pereira e; Escuissato, Dante Luiz; Irion, Klaus Loureiro; Mançano, Alexandre Dias; Nobre, Luiz Felipe; Hochhegger, Bruno; Marchiori, Edson

    2015-01-01

    Abstract Objective: To evaluate HRCT scans of the chest in 22 patients with cocaine-induced pulmonary disease. Methods: We included patients between 19 and 52 years of age. The HRCT scans were evaluated by two radiologists independently, discordant results being resolved by consensus. The inclusion criterion was an HRCT scan showing abnormalities that were temporally related to cocaine use, with no other apparent causal factors. Results: In 8 patients (36.4%), the clinical and tomographic findings were consistent with "crack lung", those cases being studied separately. The major HRCT findings in that subgroup of patients included ground-glass opacities, in 100% of the cases; consolidations, in 50%; and the halo sign, in 25%. In 12.5% of the cases, smooth septal thickening, paraseptal emphysema, centrilobular nodules, and the tree-in-bud pattern were identified. Among the remaining 14 patients (63.6%), barotrauma was identified in 3 cases, presenting as pneumomediastinum, pneumothorax, and hemopneumothorax, respectively. Talcosis, characterized as perihilar conglomerate masses, architectural distortion, and emphysema, was diagnosed in 3 patients. Other patterns were found less frequently: organizing pneumonia and bullous emphysema, in 2 patients each; and pulmonary infarction, septic embolism, eosinophilic pneumonia, and cardiogenic pulmonary edema, in 1 patient each. Conclusions: Pulmonary changes induced by cocaine use are varied and nonspecific. The diagnostic suspicion of cocaine-induced pulmonary disease depends, in most of the cases, on a careful drawing of correlations between clinical and radiological findings. PMID:26398752

  8. [Toxic cardiomyopathy due to cocaine use].

    PubMed

    Díaz, D E; Nieto, R; Brown, A; Arrocha, J A; Ramirez, J A; Acuña, E L; Blandón, R; Quiroz, J A

    1993-05-01

    The clinical record of 5 patients are studied. They were hospitalized in Santo Tomás Hospital with history of chronic and massive intoxication with inhaled and ingested cocaine. They all had cardiomegaly: in one, of grade I; in three, of grade III. The echocardiography mode B showed global cardiomegaly with dilatation of cavities and ejection fraction of 20% or below.

  9. Self-Control in Cocaine Addiction (440th Brookhaven Lecture)

    SciTech Connect

    Goldstein, Rita

    2008-10-01

    A drug-addicted person may set a goal to abstain from taking drugs, yet soon afterwards he or she will ignore all warnings or reprimands, take an excessive amount of a drug, and possibly go much farther, such as trade in a car, or another valuable possession, for a couple of cocaine hits. This disadvantageous decision-making and drug- seeking behavior may continue despite catastrophic personal consequences -- for example, loss of job, health, or family -- even when the drug is no longer perceived as pleasurable. A series of brain-mapping studies and neuropsychological tests conducted at BNL has shown that people addicted to cocaine have an impaired ability to process rewards and exercise control, in a way that is directly linked to changes in the responsiveness in their prefrontal cortex, a part of the brain essential for advantageously monitoring and controlling one's own behavior. Goldstein will describe her research in this field, which was designed to test a theoretical model postulating that drug-addicted individuals disproportionately attribute value to their drug of choice -- at the expense of other potentially but no-longer-rewarding stimuli and at the same time, experience decreased ability to inhibit their drug use.

  10. Custody of cocaine-exposed newborns: determinants of discharge decisions.

    PubMed Central

    Neuspiel, D R; Zingman, T M; Templeton, V H; DiStabile, P; Drucker, E

    1993-01-01

    OBJECTIVES. Maternal cocaine use is a leading grounds for newborn foster placement. This study was initiated to investigate the factors that predict custody status of infants born to substance-abusing women. METHODS. A retrospective cohort design was used to study the correlates of discharge custody decisions for 99 consecutive infants testing positive for cocaine in a public hospital. RESULTS. The population was 49% Black, 40% Hispanic, and 11% other or unknown. Custody at discharge was to mothers (38%), other family members (25%), or agency foster care (36%). Placement outside the family was greater when mothers had prior child welfare records, in Blacks vs others, with no prenatal care, and when mothers were younger at their first delivery or older at the index birth. Denial of custody to the mother was higher with prior child welfare involvement, in Blacks, and when the mother did not live in her own home. Both models also controlled for parity, child sex, and birthweight. CONCLUSIONS. Earlier involvement with child welfare authorities, race, and other factors predict continued separation of mothers and children at newborn discharge, suggesting the need to reexamine current policies and practices. PMID:8259803

  11. Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors.

    PubMed

    Papale, Alessandro; Morella, Ilaria Maria; Indrigo, Marzia Tina; Eugene Bernardi, Rick; Marrone, Livia; Marchisella, Francesca; Brancale, Andrea; Spanagel, Rainer; Brambilla, Riccardo; Fasano, Stefania

    2016-01-01

    Ras-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self-administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction. PMID:27557444

  12. Language Outcomes at 12 Years for Children Exposed Prenatally to Cocaine

    PubMed Central

    Lewis, Barbara A.; Minnes, Sonia; Short, Elizabeth J.; Min, Meeyoung O.; Wu, Miaoping; Lang, Adelaide; Weishampel, Paul; Singer, Lynn T.

    2014-01-01

    Purpose In this study, the authors aimed to examine the long-term effects of prenatal cocaine exposure (PCE) on the language development of 12-year-old children using a prospective design, controlling for confounding prenatal drug exposure and environmental factors. Method Children who were exposed to cocaine in utero (PCE; n = 183) and children who were not exposed to cocaine (i.e., no cocaine exposure [NCE]; n = 181) were followed prospectively from birth to 12 years of age and were compared on language subtests of the Test of Language Development—Intermediate, Third Edition (Hammill & Newcomer, 1997b), and phonological processing as measured by the Comprehensive Test of Phonological Processing (Wagner & Torgesen, 1999). The authors evaluated the relationship of PCE to language development through a multivariate analysis of covariance and regression analyses while controlling for confounders. Results Results show that PCE has small effects on specific aspects of language, including syntax and phonological processing. The caregiver variables of lower maternal vocabulary, more psychological symptoms, and a poorer home environment also had consistent effects on language and phonological processing scores. Conclusions These findings suggest that PCE continues to have small, subtle effects on specific aspects of language at age 12 years. Phonological processing skills were significantly related to the reading outcomes of letter–word identification, reading fluency, and reading comprehension, indicating that PCE also has small but lasting effects on the language skills that are related to later literacy skills. PMID:24149136

  13. Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens

    SciTech Connect

    Goeders, N.E.; Kuhar, M.J.

    1987-01-01

    A variety of clinical and animal data suggest that the repeated administration of cocaine and related psychomotor stimulants may be associated with a behavioral sensitization whereby the same dose of the drug results in increasing behavioral pathology. This investigation was designed to determine the effects of chronic cocaine administration on the binding of (/sup 3/H)sulpiride, a relatively specific ligand for D2 dopaminergic receptors, in the rat brain using in vitro homogenate binding and light microscopic quantitative autoradiographic methodologies. Chronic daily injections of cocaine (10 mg/kg, i.p.) for 15 days resulted in a significant decrease in the maximum concentration of sulpiride binding sites in the striatum and a significant increase in the maximum number of these binding sites in the nucleus accumbens. No significant differences in binding affinity were observed in either brain region. These data suggest that chronic cocaine administration may result in differential effects on D2 receptors in the nigro-striatal and mesolimbic dopaminergic systems.

  14. Are there volumetric brain differences associated with the use of cocaine and amphetamine-type stimulants?

    PubMed

    Mackey, Scott; Paulus, Martin

    2013-03-01

    While a large number of studies have examined brain volume differences associated with cocaine use, much less is known about structural differences related to amphetamine-type stimulant (ATS) use. What is known about cocaine may help to interpret emerging information on the interaction of brain volume with ATS consumption. To date, volumetric studies on the two types of stimulant have focused almost exclusively on brain differences associated with chronic use. There is considerable variability in the findings between studies which may be explained in part by the wide variety of methodologies employed. Despite this variability, seven recurrent themes are worth noting: (1) loci of lower cortical volume (approximately 10% on average) are consistently reported, (2) almost all studies indicate less volume in all or parts of the frontal cortex, (3) more specifically, a core group of studies implicate the ventromedial prefrontal cortex (including the medial portion of the orbital frontal cortex) and (4) the insula, (5) an enlarged striatal volume has been repeatedly observed, (6) reports on volume differences in the hippocampus and amygdala have been equivocal, (7) evidence supporting differential interaction of brain structure with cocaine vs. ATS is scant but the volume of all or parts of the temporal cortex appear lower in a majority of studies on cocaine but not ATS. Future research should include longitudinal designs on larger sample sizes and examine other stages of exposure to psychostimulants. PMID:23253945

  15. Are there Volumetric Brain Differences Associated with the Use of Cocaine and Amphetamine-Type Stimulants?

    PubMed Central

    Mackey, Scott; Paulus, Martin

    2013-01-01

    While a large number of studies have examined brain volume differences associated with cocaine use, much less is known about structural differences related to amphetamine-type stimulant (ATS) use. What is known about cocaine may help to interpret emerging information on the interaction of brain volume with ATS consumption. To date, volumetric studies on the two types of stimulant have focused almost exclusively on brain differences associated with chronic use. There is considerable variability in the findings between studies which may be explained in part by the wide variety of methodologies employed. Despite this variability, seven recurrent themes are worth noting: 1) loci of lower cortical volume (approximately 10% on average) are consistently reported, 2) almost all studies indicate less volume in all or parts of the frontal cortex, 3) more specifically, a core group of studies implicate the ventromedial prefrontal cortex (including the medial portion of the orbital frontal cortex) and 4) the insula, 5) an enlarged striatal volume has been repeatedly observed, 6) reports on volume differences in the hippocampus and amygdala have been equivocal, 7) evidence supporting differential interaction of brain structure with cocaine vs. ATS is scant but the volume of all or parts of the temporal cortex appear lower in a majority of studies on cocaine but not ATS. Future research should include longitudinal designs on larger sample sizes and examine other stages of exposure to psychostimulants. PMID:23253945

  16. Impairment of cocaine-mediated behaviours in mice by clinically relevant Ras-ERK inhibitors

    PubMed Central

    Papale, Alessandro; Morella, Ilaria Maria; Indrigo, Marzia Tina; Bernardi, Rick Eugene; Marrone, Livia; Marchisella, Francesca; Brancale, Andrea; Spanagel, Rainer; Brambilla, Riccardo; Fasano, Stefania

    2016-01-01

    Ras-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self-administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction. DOI: http://dx.doi.org/10.7554/eLife.17111.001 PMID:27557444

  17. Subjective sensitivity to monetary gradients is associated with frontolimbic activation to reward in cocaine abusers.

    PubMed

    Goldstein, Rita Z; Tomasi, Dardo; Alia-Klein, Nelly; Cottone, Lisa A; Zhang, Lei; Telang, Frank; Volkow, Nora D

    2007-03-16

    Drug addiction is characterized by marked disruptions in the ability to process reward. Here we evaluated in cocaine addicted and healthy control participants the subjective sensitivity to reward gradients and its association with neural responses to sustained reward. A self-report questionnaire was used to assess the former. A functional magnetic resonance imaging task that utilized monetary reward as feedback in a blocked design was used to assess the latter. Results revealed that whereas control subjects valued high money more than low money, over half of the cocaine addicted subjects valued all monetary amounts equally. This compromised subjective sensitivity to gradients in reward value was significantly correlated with higher activations to money in the lateral orbitofrontal cortex/inferior frontal gyrus (BA 47) and amygdala, and lower activations in the middle frontal gyrus (BA 6), which together explained 85% of the variability on this rating scale in the cocaine abusers only. These results provide for the first time evidence of restricted subjective sensitivity to gradients of reward in cocaine addiction and of the involvement of frontolimbic brain regions (including the orbitofrontal cortex) in this deficit.

  18. Effects of Methylphenidate on Resting-State Functional Connectivity of the Mesocorticolimbic Dopamine Pathways in Cocaine Addiction

    PubMed Central

    Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Volkow, Nora D.; Goldstein, Rita Z.

    2015-01-01

    Importance Cocaine addiction is associated with altered resting-state functional connectivity among regions of the mesocorticolimbic dopamine pathways. Methylphenidate hydrochloride, an indirect dopamine agonist, normalizes task-related regional brain activity and associated behavior in cocaine users; however, the neural systems–level effects of methylphenidate in this population have not yet been described. Objective To use resting-state functional magnetic resonance imaging to examine changes in mesocorticolimbic connectivity with methylphenidate and how connectivity of affected pathways relates to severity of cocaine addiction. Design Randomized, placebo-controlled, before-after, crossover study. Setting Clinical research center. Participants Eighteen nonabstaining individuals with cocaine use disorders. Interventions Single doses of oral methylphenidate (20 mg) or placebo were administered at each of 2 study sessions. At each session, resting scans were acquired twice: immediately after drug administration (before the onset of effects [baseline]) and 120 minutes later (within the window of peak effects). Main outcomes and Measures Functional connectivity strength was evaluated using a seed voxel correlation approach. Changes in this measure were examined to characterize the neural systems–level effects of methylphenidate; severity of cocaine addiction was assessed by interview and questionnaire. Results Short-term methylphenidate administration reduced an abnormally strong connectivity of the ventral striatum with the dorsal striatum (putamen/globus pallidus), and lower connectivity between these regions during placebo administration uniquely correlated with less severe addiction. In contrast, methylphenidate strengthened several corticolimbic and corticocortical connections. Conclusions and Relevance These findings help elucidate the neural systems–level effects of methylphenidate and suggest that short-term methylphenidate can, at least transiently

  19. A comprehensive study of sensorimotor cortex excitability in chronic cocaine users: Integrating TMS and functional MRI data☆

    PubMed Central

    Hanlon, Colleen A.; DeVries, William; Dowdle, Logan T.; West, Julia A.; Siekman, Bradley; Li, Xingbao; George, Mark S.

    2016-01-01

    Background Disruptions in motor control are often overlooked features of chronic cocaine users. During a simple sensorimotor integration task, for example, cocaine users activate a larger area of cortex than controls but have lower functional connectivity between the cortex and dorsal striatum, which is further correlated with poor performance. The purpose of this study was to determine whether abnormal cortical excitability in cocaine users was related to disrupted inhibitory or excitatory mechanisms, as measured by transcranial magnetic stimulation (TMS). Methods A battery of TMS measures were acquired from 87 individuals (50 cocaine dependent, 37 controls). Functional MRI data were acquired from a subset of 28 individuals who performed a block-design finger tapping task. Results TMS measures revealed that cocaine users had significantly higher resting motor thresholds and higher intracortical cortical facilitation (ICF) than controls. There was no between-group difference in either measure of cortical inhibition. Task-evoked BOLD signal in the motor cortex was significantly correlated with ICF in the cocaine users. There was no significant difference in brain-skull distance between groups. Conclusion These data demonstrated that cocaine users have disrupted cortical facilitation (as measured with TMS), which is related to elevated BOLD signal. Cortical inhibition, however, is largely intact. Given the relationship between ICF and glutamatergic agents, this may be a potentially fruitful and treatable target in addiction. Finally, among controls the distance from the scalp to the cortex was correlated with the motor threshold which may be a useful parameter to integrate into therapeutic TMS protocols in the future. PMID:26541870

  20. Discriminative stimulus properties of cocaine, norcocaine, and N-allylnorcocaine.

    PubMed

    Bedford, J A; Nail, G L; Borne, R F; Wilson, M C

    1981-01-01

    A discriminative stimulus paradigm was employed to train eight male and female Wistar rats to discriminate 5.0 mg/kg cocaine HCl from 2.0 ml/kg saline. Subjects responded in a two bar operant chamber on an FR 30 schedule for food reinforcement. All sessions followed a 10 minute pretreatment with either saline, the training dose of cocaine, four probe doses of cocaine HCl (1.0, 2.5, 7.5, 10 mg/kg), four probe doses of norcocaine (1.0, 2.5, 5.0, 7.5 mg/kg) or four probe doses of N-allylnorcocaine (5.0, 7.5, 10, 20 mg/kg). All probe doses were treated using an extinction procedure. The three highest doses of cocaine generalized to cocaine while the 1.0 mg/kg dose of cocaine generalized to saline. The two highest doses of norcocaine generalized to cocaine while the 2.5 mg/kg dose of norcocaine resulted in 57% responding on the cocaine lever with the 1.0 mg/kg dose generalizing to saline. Only the highest dose of N-allylnorcocaine was found to generalize to cocaine with the intermediate doses resulting in an intermediate level of responding occurring on the cocaine lever. The 5.0 mg/kg dose of N-allylnorcocaine generalized to saline.

  1. Cocaine and kidney injury: a kaleidoscope of pathology

    PubMed Central

    Goel, Narender; Pullman, James M.; Coco, Maria

    2014-01-01

    Cocaine is abused worldwide as a recreational drug. It is a potent activator of the sympathetic nervous system leading to intense vasoconstriction, endothelial dysfunction, oxidative stress, platelet activation and decrease in prostaglandins E2 and prostacyclin. Cocaine can lead to widespread systemic adverse effects such as stroke, myocardial infarction, arterial dissection, vascular thrombosis and rhabdomyolysis. In human and rat kidneys, cocaine has been associated with glomerular, tubular, vascular and interstitial injury. It is not uncommon to diagnose cocaine-related acute kidney injury (AKI), malignant hypertension and chronic kidney disease. Cocaine abuse can lead to AKI by rhabdomyolysis, vasculitis, infarction, thrombotic microangiopathy and malignant hypertension. It is reported that 50–60% of people who use both cocaine and heroin are at increased risk of HIV, hepatitis and additional risk factors that can cause kidney diseases. While acute interstitial nephritis (AIN) is a known cause of AKI, an association of AIN with cocaine is unusual and seldom reported. We describe a patient with diabetes mellitus, hypertension and chronic hepatitis C, who presented with AKI. Urine toxicology was positive for cocaine and a kidney biopsy was consistent with AIN. Illicit drugs such as cocaine or contaminants may have caused AIN in this case and should be considered in the differential diagnosis of causes of AKI in a patient with substance abuse. We review the many ways that cocaine adversely impacts on kidney function. PMID:25859366

  2. Neuroplasticity in the mesolimbic dopamine system and cocaine addiction

    PubMed Central

    Thomas, M J; Kalivas, P W; Shaham, Y

    2008-01-01

    The main characteristics of cocaine addiction are compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. A current popular hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced neuroadaptations in reward-related learning and memory processes, which cause hypersensitivity to cocaine-associated cues, impulsive decision making and abnormal habit-like learned behaviours that are insensitive to adverse consequences. Here, we review results from studies on the effect of cocaine exposure on selected signalling cascades, growth factors and physiological processes previously implicated in neuroplasticity underlying normal learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We also discuss the degree to which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on how these factors may interact to initiate and sustain cocaine psychomotor sensitization and cocaine seeking. PMID:18345022

  3. Cocaethylene formation following ethanol and cocaine administration by different routes.

    PubMed

    Herbst, Ellen D; Harris, Debra S; Everhart, E Thomas; Mendelson, John; Jacob, Peyton; Jones, Reese T

    2011-04-01

    Ethanol alters the hepatic biotransformation of cocaine, resulting in transesterification to a novel active metabolite, cocaethylene. Because of first pass metabolism, oral drug administration might be expected to produce relatively larger concentrations of cocaethylene than would intravenous or smoked administration. We, therefore, compared the effects of route of cocaine administration on the formation and elimination of cocaethylene. Six experienced cocaine users were tested in 6 sessions, approximately 1 week apart. Deuterium-labeled cocaine (d₅) was administered in all conditions. Oral cocaine-d₅ 2.0 mg/kg, intravenous cocaine-d₅ 1.0 mg/kg, and smoked cocaine-d₅ (200 mg) were administered after oral ethanol 1.0 g/kg or placebo. A small, intravenous dose of deuterated cocaethylene (d₃) also was administered with all conditions for determination of cocaethylene formation. Physiologic and subjective effects were recorded and plasma cocaine-d₅, cocaethylene-d₅, cocaethylene-d₃, and benzoylecgonine-d₅ were measured by gas chromatography-mass spectrometry. About 24% (± 11) of intravenous cocaine was converted to cocaethylene. The oral route (34% ± 20) was significantly greater than from the smoked route (18% ± 11) and showed a trend toward significance for greater formation of cocaethylene compared to the intravenous route. Within each route, the cocaine-ethanol combination produced greater increases in heart rate and rate-pressure product than cocaine alone. Global intoxication effects across time after smoking or intravenous administration were significantly greater when cocaine and ethanol were both given. Administration of cocaine by different routes alters the amount of cocaethylene formed through hepatic first-pass effects. Increased cardiovascular and subjective effects might explain the toxicity and popularity of the combined drugs. PMID:21463066

  4. The Role of Acetylcholine in Cocaine Addiction

    PubMed Central

    Williams, Mark J; Adinoff, Bryon

    2008-01-01

    Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic

  5. Toxic effects of prenatal exposure to alcohol, tobacco and other drugs.

    PubMed

    Scott-Goodwin, A C; Puerto, M; Moreno, I

    2016-06-01

    Tobacco, alcohol, cannabis and cocaine are the most consumed psychoactive drugs throughout the population. Prenatal exposure to these drugs could alter normal foetal development and could threaten future welfare. The main changes observed in prenatal exposure to tobacco are caused by nicotine and carbon monoxide, which can impede nutrient and oxygen exchange between mother and foetus, restricting foetal growth. Memory, learning processes, hearing and behaviour can also be affected. Alcohol may cause physical and cognitive alterations in prenatally exposed infants, fundamentally caused by altered NMDAR and GABAR activity. Tetrahydrocannabinol, the psychoactive compound of cannabis, is capable of activating CB1R, inducing connectivity deficits during the foetal brain development. This fact could be linked to behavioural and cognitive deficits. Many of the effects from prenatal cocaine exposure are caused by altered cell proliferation, migration, differentiation and dendritic growth processes. Cocaine causes long term behavioural and cognitive alterations and also affects the uteroplacental unit.

  6. Toxic effects of prenatal exposure to alcohol, tobacco and other drugs.

    PubMed

    Scott-Goodwin, A C; Puerto, M; Moreno, I

    2016-06-01

    Tobacco, alcohol, cannabis and cocaine are the most consumed psychoactive drugs throughout the population. Prenatal exposure to these drugs could alter normal foetal development and could threaten future welfare. The main changes observed in prenatal exposure to tobacco are caused by nicotine and carbon monoxide, which can impede nutrient and oxygen exchange between mother and foetus, restricting foetal growth. Memory, learning processes, hearing and behaviour can also be affected. Alcohol may cause physical and cognitive alterations in prenatally exposed infants, fundamentally caused by altered NMDAR and GABAR activity. Tetrahydrocannabinol, the psychoactive compound of cannabis, is capable of activating CB1R, inducing connectivity deficits during the foetal brain development. This fact could be linked to behavioural and cognitive deficits. Many of the effects from prenatal cocaine exposure are caused by altered cell proliferation, migration, differentiation and dendritic growth processes. Cocaine causes long term behavioural and cognitive alterations and also affects the uteroplacental unit. PMID:27037188

  7. The Design of Laboratory Experiments in the 1980s: A Case Study on the Oxidation of Alcohols with Household Bleach.

    ERIC Educational Resources Information Center

    Mohrig, Jerry R.; And Others

    1985-01-01

    Discusses the rationale for and development of an experiment on the oxidation of secondary alcohols with common hypochlorite bleach. The experiment provides a safe, environmentally sound, and inexpensive modern synthetic method. In addition, it utilizes a variety of laboratory techniques and some fundamental oxidation-reduction chemistry. (JN)

  8. Cocaine and specific cocaine metabolites induce von Willebrand Factor release from endothelial cells in a tissue-specific manner

    PubMed Central

    Hobbs, William E.; Moore, Emily E.; Penkala, Rebecca A.; Bolgiano, D.; López, José A.

    2013-01-01

    Objective Cocaine use is associated with arterial thrombosis, including myocardial infarction and stroke. Cocaine use results in increased plasma von Willebrand Factor (VWF), accelerated atherosclerosis, and platelet-rich arterial thrombi, suggesting that cocaine activates the endothelium, promoting platelet-VWF interactions. Approach and Results Human umbilical vein (HUVEC), brain microvasculature (BMVEC), or coronary artery (CAEC) endothelial cells were treated with cocaine or metabolites benzoylecgonine, cocaethylene, norcocaine, or ecgonine methylester. Supernatant VWF concentration and multimer structure were measured, and platelet–VWF strings formed on the endothelial surface under flow were quantified. Cocaine, benzoylecgonine, and cocaethylene induced endothelial VWF release, with the two metabolites being more potent than the parent molecule. BMVEC were more sensitive to cocaine and metabolites than were HUVEC or CAEC. CAEC released VWF into the supernatant but did not form VWF–platelet strings. Intracellular cAMP concentration was not increased after treatment with cocaine or its metabolites. Conclusions Both cocaine and metabolites benzoylecgonine and cocaethylene induced endothelial VWF secretion, possibly explaining thrombotic risk after cocaine ingestion. VWF secretion is likely to vary between vascular beds, with brain endothelial cells being particularly sensitive. These results suggest that clinical management of cocaine-induced ischemia may benefit from therapies aimed at disrupting the VWF–platelet interaction. PMID:23539221

  9. Certain or uncertain cocaine expectations influence accumbens dopamine responses to self-administered cocaine and non-rewarded operant behavior.

    PubMed

    D'Souza, Manoranjan S; Duvauchelle, Christine L

    2008-09-01

    Uncertainty and errors in predicting natural rewards influence associative learning and dopamine activity. The present study was conducted to determine the influence of cue-induced cocaine uncertainty, certainty and prediction error on nucleus accumbens dopamine (NAcc DA) in rats. For Certainty training, distinctive sensory cues were present during cocaine availability and alternate cues were paired with non-reinforced (saline) operant sessions. For Uncertainty training, all cues were equally associated with both cocaine and non-reinforcement. After training, animals self-administered cocaine or saline in the presence of conditioned cues while NAcc DA responses were assessed using in vivo microdialysis. Findings revealed cocaine-stimulated NAcc DA increased significantly less in Certainty--compared to Uncertainty-trained animals, and cocaine-paired cues in the absence of cocaine (Negative Prediction Error) resulted in a significant depression of baseline NAcc DA. These findings provide support for enhanced DA activity during cocaine uncertainty or the development of conditioned cocaine tolerance in subjects certain of a cocaine outcome.

  10. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    SciTech Connect

    Som, P.; Wang, G.J.; Oster, Z.H.; Knapp, F.F. Jr.; Yonekura, Y.; Fujibayashi, Y.; Yamamoto, K.; Kubota, K.

    1992-12-31

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  11. Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

    SciTech Connect

    Som, P.; Wang, G.J. ); Oster, Z.H. ); Knapp, F.F. Jr. ); Yonekura, Y. . Faculty of Medicine); Fujibayashi, Y. . Hospital); Yamamoto, K. . Medical School); Kubota, K. (Tohoku Univ., Sendai

    1992-01-01

    Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.

  12. Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking.

    PubMed

    Wong, Wai Chong; Marinelli, Michela

    2016-05-01

    Adolescent rats take cocaine more readily than adults, are more sensitive to lower doses of the drug and work harder for it. It remains unknown if adolescent-onset of cocaine use has long-term consequences on adult relapse liability. Therefore, we tested if self-administering cocaine during adolescence impacts subsequent stress-induced reinstatement to cocaine seeking and taking, after a prolonged drug-free period. Adolescent (~P42) or adult (P88) rats self-administered cocaine (0.6 or 1.2 mg/kg/infusion) for 7 or 10 days. Then, they underwent a prolonged drug-free period (21-40 days), after which they were tested for reinstatement of cocaine-seeking (i.e. responding in the absence of cocaine) induced by the stress hormone corticosterone, the pharmacological stressor yohimbine or electric footshock. Studies employed either single extinction session (within-session extinction/reinstatement) or repeated extinction prior to reinstatement (between-session extinction/reinstatement). Finally, in a separate set of experiments, rats underwent a prolonged drug-free period (~40 days) and were then allowed to self-administer cocaine again, using progressive-ratio procedures that appraise the reinforcing efficacy of cocaine. Rats with adolescent-onset of cocaine use showed greater stress-induced reinstatement of cocaine seeking than rats with adult-onset of cocaine use. This was observed across conditions, providing external validity to these results. Groups did not differ on drug taking in progressive-ratio tests. Our studies indicate that experiencing cocaine during adolescence renders subjects particularly responsive to the subsequent effects of stress on drug seeking. This heightened propensity for reinstatement puts adolescent-onset drug users at heightened risk for relapse.

  13. Chronic Cocaine Dampens Dopamine Signaling during Cocaine Intoxication and Unbalances D1 over D2 Receptor Signaling

    PubMed Central

    Park, Kicheon; Pan, Yingtian

    2013-01-01

    Dopamine increases triggered by cocaine and consequent stimulation of dopamine receptors (including D1 and D2) are associated with its rewarding effects. However, while facilitation of D1 receptor (D1R) signaling enhances the rewarding effects of cocaine, facilitation of D2R signaling decreases it, which indicates that for cocaine to be rewarding it must result in a predominance of D1R over D2R signaling. Moreover, the transition to compulsive cocaine intake might result from an imbalance between D1R and D2R signaling. To test the hypothesis that chronic cocaine use unbalances D1R over D2R signaling during cocaine intoxication, we used microprobe optical imaging to compare dynamic changes in intracellular calcium ([Ca2+]i, marker of neuronal activation) to acute cocaine in striatal D1R-EGFP and D2R-EGFP-expressing neurons between control and chronically treated mice. Chronic cocaine attenuated responses to acute cocaine in D1R (blunting Ca2+ increases by 67 ± 16%) and D2R (blunting Ca2+ decrease by 72 ± 17%) neurons in most D1R and D2R neurons (∼75%). However, the dynamics of this attenuation during cocaine intoxication was longer lasting for D2R than for D1R. Thus, whereas control mice showed a fast but short-lasting predominance of D1R over D2R signaling (peaking at ∼8 min) during acute cocaine intoxication, in chronically treated mice D1R predominance was sustained for >30 min (throughout the measurement period). Thus, chronic cocaine use dramatically reduced cocaine-induced DA signaling, shifting the balance between D1R and D2R signaling during intoxication to a predominance of D1R (stimulatory) over D2R (inhibitory) signaling, which might facilitate compulsive intake in addiction. PMID:24089490

  14. Adolescent-onset of cocaine use is associated with heightened stress-induced reinstatement of cocaine seeking.

    PubMed

    Wong, Wai Chong; Marinelli, Michela

    2016-05-01

    Adolescent rats take cocaine more readily than adults, are more sensitive to lower doses of the drug and work harder for it. It remains unknown if adolescent-onset of cocaine use has long-term consequences on adult relapse liability. Therefore, we tested if self-administering cocaine during adolescence impacts subsequent stress-induced reinstatement to cocaine seeking and taking, after a prolonged drug-free period. Adolescent (~P42) or adult (P88) rats self-administered cocaine (0.6 or 1.2 mg/kg/infusion) for 7 or 10 days. Then, they underwent a prolonged drug-free period (21-40 days), after which they were tested for reinstatement of cocaine-seeking (i.e. responding in the absence of cocaine) induced by the stress hormone corticosterone, the pharmacological stressor yohimbine or electric footshock. Studies employed either single extinction session (within-session extinction/reinstatement) or repeated extinction prior to reinstatement (between-session extinction/reinstatement). Finally, in a separate set of experiments, rats underwent a prolonged drug-free period (~40 days) and were then allowed to self-administer cocaine again, using progressive-ratio procedures that appraise the reinforcing efficacy of cocaine. Rats with adolescent-onset of cocaine use showed greater stress-induced reinstatement of cocaine seeking than rats with adult-onset of cocaine use. This was observed across conditions, providing external validity to these results. Groups did not differ on drug taking in progressive-ratio tests. Our studies indicate that experiencing cocaine during adolescence renders subjects particularly responsive to the subsequent effects of stress on drug seeking. This heightened propensity for reinstatement puts adolescent-onset drug users at heightened risk for relapse. PMID:26202521

  15. Effects of progesterone and testosterone on cocaine self-administration and cocaine discrimination by female rhesus monkeys.

    PubMed

    Mello, Nancy K; Knudson, Inge M; Kelly, Maureen; Fivel, Peter A; Mendelson, Jack H

    2011-10-01

    The neuroactive steroid hormone progesterone attenuates cocaine's abuse-related effects in women and in rodents under some conditions, but the effects of testosterone are unknown. We compared the acute effects of progesterone (0.1, 0.2, and 0.3 mg/kg, intramuscularly (i.m.)), testosterone (0.001, 0.003, and 0.01 mg/kg, i.m.), and placebo on cocaine self-administration and cocaine discrimination dose-effect curves in female rhesus monkeys. Cocaine self-administration (0.03 mg/kg per inj.) was maintained on a fixed ratio 30 schedule of reinforcement, and monkeys had unlimited access to cocaine for 2 h each day. Cocaine doses were administered in an irregular order during each dose-effect curve determination, and the same dose order was used in each subject in all treatment conditions. Blood samples for hormone analysis were collected at the end of each test session. Banana-flavored food pellets (1 g) were also available in three 1-h daily sessions. In drug discrimination studies, the effects of pretreatment with progesterone (0.032-0.32 mg/kg, i.m.) and testosterone (0.001-0.01 mg/kg, i.m.) on the discriminative stimulus effects of cocaine (0.18 mg/kg, i.m.) were examined. Progesterone and testosterone did not alter cocaine discrimination, and did not substitute for cocaine. In contrast, progesterone and testosterone each significantly decreased cocaine self-administration, and produced a downward and rightward shift in the cocaine self-administration dose-effect curve. These findings are concordant with clinical reports that progesterone administration may decrease ratings of positive subjective effects of cocaine in women, and suggest the possible value of neuroactive steroid hormones for the treatment of cocaine abuse and reduction of risk for relapse. PMID:21796112

  16. Substituting a long-acting dopamine uptake inhibitor for cocaine prevents relapse to cocaine seeking.

    PubMed

    Velázquez-Sánchez, Clara; Ferragud, Antonio; Ramos-Miguel, Alfredo; García-Sevilla, Jesús A; Canales, Juan J

    2013-07-01

    The treatment of cocaine addiction remains a challenge. The dopamine replacement approach in cocaine addiction involves the use of a competing dopaminergic agonist that might suppress withdrawal and drug craving in abstinent individuals. Although it has long been postulated that such an approach may be therapeutically successful, preclinical or clinical evidence showing its effectiveness to prevent relapse is scant. We used in rats a procedure that involved substitution of the N-substituted benztropine analog 3α-[bis(4'-fluorophenyl)methoxy]-tropane (AHN-1055), a long-acting dopamine uptake inhibitor (DUI), for cocaine. Maintenance treatment was self-administered. After extinction, reinstatement of drug seeking was induced by cocaine priming. We measured the contents of brain-derived neurotrophic factor (BDNF), c-Fos and Fas-associated death domain (FADD) proteins in the medial prefrontal cortex (mPFC) following reinstatement. DUI, but not amphetamine, substitution led to extinction of active lever presses, as did saline substitution. DUI substitution significantly reduced cocaine-induced reinstatement of drug-seeking behavior, which was strongly elicited after saline substitution. Rats passively yoked to DUI also showed reduced cocaine-primed reinstatement. Reductions in drug seeking during reinstatement were matched by downward shifts in the contents of BDNF, c-Fos and FADD proteins in the mPFC, which were elevated in relapsing rats. These data indicate that DUI substitution not only leads to extinction of self-administration behavior but also prevents reinstatement of drug seeking induced by cocaine re-exposure. Thus, DUI substitution therapy using compounds with low abuse potential, even if received passively in the context previously paired with drug taking, may provide an effective treatment for stimulant addiction.

  17. High alcohol intake in female Sardinian alcohol-preferring rats.

    PubMed

    Loi, Barbara; Colombo, Giancarlo; Maccioni, Paola; Carai, Mauro A M; Franconi, Flavia; Gessa, Gian Luigi

    2014-06-01

    Sardinian alcohol-preferring (sP) rats have been selectively bred for high alcohol preference and consumption. When exposed to the standard, home cage 2-bottle "alcohol (10%, v/v) vs. water" choice regimen with continuous access, male sP rats consume daily approximately 6 g/kg alcohol. Conversely, when exposed to the intermittent (once every other day) access to 2 bottles containing alcohol (20%, v/v) and water, respectively, male sP rats display marked increases in daily alcohol intake and signs of alcohol intoxication and "behavioral" dependence. The present study was designed to assess alcohol intake in female sP rats exposed, under the 2-bottle choice regimen, to (a) 10% (v/v) alcohol with continuous access (CA10%), (b) 10% (v/v) alcohol with intermittent access (IA10%), (c) 20% (v/v) alcohol with continuous access (CA20%), and (d) 20% (v/v) alcohol with intermittent access (IA20%). Male sP rats (exposed to CA10% and IA20% conditions) were included for comparison. Over 20 daily drinking sessions, daily alcohol intake in female CA10% and IA20% rats averaged 7.0 and 9.6 g/kg, respectively. The rank of alcohol intake was IA20% > IA10% = CA20% > CA10%. Conversely, daily alcohol intake in male CA10% and IA20% rats averaged 6.0 and 8.2 g/kg, respectively. Comparison of female and male rats yielded the following rank of alcohol intake: female IA20% > male IA20% > female CA10% ≥ male CA10%. An additional experiment found that alcohol drinking during the first hour of the drinking session produced mean blood alcohol levels of 35-40 mg% and 85-100 mg% in the CA10% and IA20% rats, respectively. These results (a) extend to female sP rats previous data demonstrating the capacity of the IA20% condition to markedly escalate alcohol drinking, and (b) demonstrate that female sP rats consume more alcohol than male sP rats. This sex difference is more evident under the IA20% condition, suggesting that female sP rats are highly sensitive to the promoting effect

  18. Effect expectancies for cocaine intoxication: initial vs. descendent phases.

    PubMed

    Schafer, J; Fals-Stewart, W

    1993-01-01

    This study examined the association between proximal vs. distal effect expectancies for cocaine consumption in a college student population with (N = 26) and without (N = 69) cocaine experience. Participants completed the Cocaine Effect Expectancy Questionnaire-Likert (CEEQL) and were asked to respond to each item twice: first, their belief about that specific effect during the initial phase of cocaine intoxication; and second, in relation to their belief about that effect during the descendent period. Positive and negative scales were scored for each subject. Positive expectancies were not associated between the two time points, while negative expectancies were. Users reported significantly less negative expected effects of cocaine, while nonusers and users held similar beliefs about the positive effects of cocaine. This latter effect was replicated in an independent sample (N = 140).

  19. Inhalational model of cocaine exposure in mice: neuroteratological effects.

    PubMed

    He, Fang; Lidow, Irina A; Lidow, Michael S

    2006-01-01

    We developed a novel inhalation-based mouse model of prenatal cocaine exposure. This model approximates cocaine abuse via smoking, the preferred route of cocaine administration by heavy drug users. The model is also characterized by (i) absence of procedural stress from drug administration, (ii) long-term drug exposure starting weeks before pregnancy and continuing throughout the entire gestation, and (iii) self-administration of cocaine in multi-hour daily sessions reminiscent of drug binges, which allows animals to set up the levels of their own drug consumption. The offspring of female mice inhaling cocaine in our model displayed no gross alterations in their cortical cytoarchitecture. These offspring, however, showed significant impairments in sustained attention and spatial working memory. We hope that the introduction of the present model will lead to a significant increase in our understanding of outcomes of prenatal cocaine exposure. PMID:16414242

  20. Effect expectancies for cocaine intoxication: initial vs. descendent phases.

    PubMed

    Schafer, J; Fals-Stewart, W

    1993-01-01

    This study examined the association between proximal vs. distal effect expectancies for cocaine consumption in a college student population with (N = 26) and without (N = 69) cocaine experience. Participants completed the Cocaine Effect Expectancy Questionnaire-Likert (CEEQL) and were asked to respond to each item twice: first, their belief about that specific effect during the initial phase of cocaine intoxication; and second, in relation to their belief about that effect during the descendent period. Positive and negative scales were scored for each subject. Positive expectancies were not associated between the two time points, while negative expectancies were. Users reported significantly less negative expected effects of cocaine, while nonusers and users held similar beliefs about the positive effects of cocaine. This latter effect was replicated in an independent sample (N = 140). PMID:8506788

  1. Design and Synthesis of Systemically Active Metabotropic Glutamate Subtype-2 and -3 (mGlu2/3) Receptor Positive Allosteric Modulators (PAMs): Pharmacological Characterization and Assessment in a Rat Model of Cocaine Dependence

    PubMed Central

    2015-01-01

    As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure–activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4–8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology. PMID:24735492

  2. Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): pharmacological characterization and assessment in a rat model of cocaine dependence.

    PubMed

    Dhanya, Raveendra-Panickar; Sheffler, Douglas J; Dahl, Russell; Davis, Melinda; Lee, Pooi San; Yang, Li; Nickols, Hilary Highfield; Cho, Hyekyung P; Smith, Layton H; D'Souza, Manoranjan S; Conn, P Jeffrey; Der-Avakian, Andre; Markou, Athina; Cosford, Nicholas D P

    2014-05-22

    As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology. PMID:24735492

  3. Contingency management in cocaine abusers: a dose-effect comparison of goods-based versus cash-based incentives.

    PubMed

    Vandrey, Ryan; Bigelow, George E; Stitzer, Maxine L

    2007-08-01

    Goods-based contingency management interventions (e.g., those using vouchers or prizes as incentives) have demonstrated efficacy in reducing cocaine use, but cost has limited dissemination to community clinics. Recent research suggests that development of a cash-based contingency management approach may improve treatment outcomes while reducing operational costs of the intervention. However, the clinical safety of providing cash-based incentives to substance abusers has been a concern. The present 16-week study compared the effects of goods-based versus cash-based incentives worth $0, $25, $50, and $100 on short-term cocaine abstinence in a small sample of cocaine-dependent methadone patients (N = 12). A within-subject design was used; a 9-day washout period separated each of 8 incentive conditions. Higher magnitude ($50 and $100) cash-based incentives (checks) produced greater cocaine abstinence compared with the control ($0) condition, but a magnitude effect was not seen for goods-based incentives (vouchers). A trend was observed for greater rates of abstinence in the cash-based versus goods-based incentives at the $50 and $100 magnitudes. Receipt of $100 checks did not increase subsequent rates of cocaine use above those seen in control conditions. The efficacy and safety data provided in this and other recent studies suggest that use of cash-based incentives deserves consideration for clinical applications of contingency management, but additional confirmation in research using larger samples and more prolonged periods of incentive delivery is needed.

  4. Proteomic analysis of the nucleus accumbens of rats with different vulnerability to cocaine addiction.

    PubMed

    del Castillo, Carmen; Morales, Lidia; Alguacil, Luis F; Salas, Elisabet; Garrido, Elisa; Alonso, Elba; Pérez-García, Carmen

    2009-07-01

    Vulnerability to the addictive effects of drugs of abuse varies among individuals, but the biological basis of these differences are poorly known. This work tries to increase this knowledge by comparing the brain proteome of animals with different rate of extinction of cocaine-seeking behaviour. To achieve this goal, we used a place-preference paradigm to separate Sprague Dawley rats in two groups: rats that extinguished (E) and rats that did not extinguish (NE) cocaine-seeking behaviour after a five-day period of drug abstinence. Once the phenotype was established, we compared the protein expression in the nucleus accumbens (NAC) of these animals after a single injection of either saline (SAL) or cocaine (COC, 15 mg/kg). The analysis of protein expression was performed by 2-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time of flight mass spectrometry. When comparing E SAL and NE SAL animals we found significant differences in the expression level of 5 proteins: ATP synthase subunit alpha, fumarate hydratase, transketolase, NADH dehydrogenase [ubiquinone] flavoprotein 2 and glutathione transferase omega-1. A single injection of COC differently alters the NAC proteome of E and NE rats; thus in E COC animals there was an alteration in the expression of 6 proteins, including dihydropyrimidinase-related protein 2 and NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10; whereas in NE COC rats 9 proteins were altered (including alpha-synuclein, peroxiredoxin-2 and peroxiredoxin-5). These proteins could be potential biomarkers of individual vulnerability to cocaine abuse and may be helpful in designing new treatments for cocaine addiction.

  5. Effects of intranasal cocaine on sympathetic nerve discharge in humans.

    PubMed Central

    Jacobsen, T N; Grayburn, P A; Snyder, R W; Hansen, J; Chavoshan, B; Landau, C; Lange, R A; Hillis, L D; Victor, R G

    1997-01-01

    Cocaine-induced cardiovascular emergencies are mediated by excessive adrenergic stimulation. Animal studies suggest that cocaine not only blocks norepinephrine reuptake peripherally but also inhibits the baroreceptors, thereby reflexively increasing sympathetic nerve discharge. However, the effect of cocaine on sympathetic nerve discharge in humans is unknown. In 12 healthy volunteers, we recorded blood pressure and sympathetic nerve discharge to the skeletal muscle vasculature using intraneural microelectrodes (peroneal nerve) during intranasal cocaine (2 mg/kg, n = 8) or lidocaine (2%, n = 4), an internal local anesthetic control, or intravenous phenylephrine (0.5-2.0 microg/kg, n = 4), an internal sympathomimetic control. Experiments were repeated while minimizing the cocaine-induced rise in blood pressure with intravenous nitroprusside to negate sinoaortic baroreceptor stimulation. After lidocaine, blood pressure and sympathetic nerve discharge were unchanged. After cocaine, blood pressure increased abruptly and remained elevated for 60 min while sympathetic nerve discharge initially was unchanged and then decreased progressively over 60 min to a nadir that was only 2+/-1% of baseline (P < 0.05); however, plasma venous norepinephrine concentrations (n = 5) were unchanged up to 60 min after cocaine. Sympathetic nerve discharge fell more rapidly but to the same nadir when blood pressure was increased similarly with phenylephrine. When the cocaine-induced increase in blood pressure was minimized (nitroprusside), sympathetic nerve discharge did not decrease but rather increased by 2.9 times over baseline (P < 0.05). Baroreflex gain was comparable before and after cocaine. We conclude that in conscious humans the primary effect of intranasal cocaine is to increase sympathetic nerve discharge to the skeletal muscle bed. Furthermore, sinoaortic baroreflexes play a pivotal role in modulating the cocaine-induced sympathetic excitation. The interplay between these

  6. Maternal cocaine use without evidence of fetal exposure.

    PubMed

    Potter, S; Klein, J; Valiante, G; Stack, D M; Papageorgiou, A; Stott, W; Lewis, D; Koren, G; Zelazo, P R

    1994-10-01

    We report a case of lack of fetal exposure to cocaine and benzoylecgonine as evidenced by meconium and hair analysis, but exposure to nicotine and its metabolite cotinine, after extensive maternal use of cocaine and nicotine. These data suggest that the mode of maternal use of cocaine and individual differences in placental handling of the drug may protect some fetuses, and highlight the need to address interpatient variability.

  7. Racial and Ethnic Differences in Alcohol and Other Drug Use. Infofacts/Resources

    ERIC Educational Resources Information Center

    Higher Education Center for Alcohol and Other Drug Abuse and Violence Prevention, 2008

    2008-01-01

    Contrary to stereotypes seen in the media, several studies have found use of alcohol and other substances among racial and ethnic minority college students to be lower than among white students. At historically black colleges, for instance, about half the percentage of students report using tobacco, marijuana, or cocaine compared with students at…

  8. [On the surface-anesthetic activity of some ether alcohols (author's transl)].

    PubMed

    Riemschneider, R; Rufer, C; Chik, W H

    1978-01-01

    An account of the preparation and surface anesthetic potency of 12 ether alcohols of the type X-O-Y-OH is given in this paper. The anaesthetic intensity and effective duration of a chloronaphthalene derivative of this type lie within the range of action of cocain.

  9. Overview of Alcohol Consumption

    MedlinePlus

    ... Search Alcohol & Your Health Overview of Alcohol Consumption Alcohol's Effects on the Body Alcohol Use Disorder Fetal Alcohol ... other questions about alcohol. Here’s what we know: Alcohol’s effects vary from person to person, depending on a ...

  10. Alcohol and pregnancy

    MedlinePlus

    Drinking alcohol during pregnancy; Fetal alcohol syndrome - pregnancy; FAS - fetal alcohol syndrome ... When a pregnant woman drinks alcohol, the alcohol travels through her blood and into the baby's blood, tissues, and organs. Alcohol breaks down much more slowly in ...

  11. Development of translational preclinical models in substance abuse: Effects of cocaine administration on cocaine choice in humans and non-human primates.

    PubMed

    Foltin, Richard W; Haney, Margaret; Rubin, Eric; Reed, Stephanie C; Vadhan, Nehal; Balter, Rebecca; Evans, Suzette M

    2015-07-01

    Human drug use involves repeated choices to take drugs or to engage in alternative behaviors. The purpose of this study was to examine how response cost for cocaine and the value of an alternative reinforcer (opportunity to play a game of chance) and how 'free' doses (with minimal response cost) affected cocaine choice. Two laboratory studies of cocaine self-administration were conducted in a group of humans who were habitual cocaine smokers and in a group of rhesus monkeys that intravenously self-administered cocaine. Nine human cocaine smokers who were not seeking treatment for their cocaine were repeatedly presented with the choice to smoke 25mg cocaine base or play a game of chance for a monetary bonus paid at study completion. The response cost for choosing cocaine varied (up to 4000 responses/dose) and the number of game plays varied (up to 8). In this sample of humans, increasing either the response cost for cocaine or increasing the value of the alternative reinforcer did not significantly affect cocaine choice, while increasing both simultaneously slightly decreased cocaine choice and increased choice of the alternative. In monkeys, the dose-response function for cocaine self-administration (10 choices of 0.0125-0.1mg/kg/infusion vs. candy coated chocolate) was steep and we failed to achieve a 50/50 cocaine/candy choice even after substantially manipulating cost and number of candies available. Providing a large 'free' self-administered cocaine dose to humans did not significantly affect cocaine choice, whereas in monkeys, a large free dose of cocaine decreased cocaine choice when higher doses of cocaine were available for self-administration. The present results demonstrate that in the laboratory, it is difficult to modify on-going cocaine self-administration behavior in both humans and non-human primates.

  12. Development of translational preclinical models in substance abuse: Effects of cocaine administration on cocaine choice in humans and non-human primates.

    PubMed

    Foltin, Richard W; Haney, Margaret; Rubin, Eric; Reed, Stephanie C; Vadhan, Nehal; Balter, Rebecca; Evans, Suzette M

    2015-07-01

    Human drug use involves repeated choices to take drugs or to engage in alternative behaviors. The purpose of this study was to examine how response cost for cocaine and the value of an alternative reinforcer (opportunity to play a game of chance) and how 'free' doses (with minimal response cost) affected cocaine choice. Two laboratory studies of cocaine self-administration were conducted in a group of humans who were habitual cocaine smokers and in a group of rhesus monkeys that intravenously self-administered cocaine. Nine human cocaine smokers who were not seeking treatment for their cocaine were repeatedly presented with the choice to smoke 25mg cocaine base or play a game of chance for a monetary bonus paid at study completion. The response cost for choosing cocaine varied (up to 4000 responses/dose) and the number of game plays varied (up to 8). In this sample of humans, increasing either the response cost for cocaine or increasing the value of the alternative reinforcer did not significantly affect cocaine choice, while increasing both simultaneously slightly decreased cocaine choice and increased choice of the alternative. In monkeys, the dose-response function for cocaine self-administration (10 choices of 0.0125-0.1mg/kg/infusion vs. candy coated chocolate) was steep and we failed to achieve a 50/50 cocaine/candy choice even after substantially manipulating cost and number of candies available. Providing a large 'free' self-administered cocaine dose to humans did not significantly affect cocaine choice, whereas in monkeys, a large free dose of cocaine decreased cocaine choice when higher doses of cocaine were available for self-administration. The present results demonstrate that in the laboratory, it is difficult to modify on-going cocaine self-administration behavior in both humans and non-human primates. PMID:25933796

  13. Genetic variants