Circadian rhythms in effects of hypnotics and sleep inducers.

PubMed

Reinberg, A

1986-01-01

Chronopharmacology involves the investigation of drug effects as a function of biological time and the investigation of drug effects on rhythm characteristics. Three new concepts must be considered: (a) the chronokinetics of a drug, embracing rhythmic (circadian) changes in drug bioavailability (or pharmacokinetics) and its excretion (urinary among others); (b) the chronaesthesia of a biosystem to a drug, i.e. circadian changes in the susceptibility of any biosystem to a drug (including organ systems, parasites, etc.); skin and bronchial chronaesthesia to various agents have been documented in man; and (c) the chronergy of a drug, taking into consideration its chronokinetics and the chronaesthesia of the involved organismic biosystems. The term chronergy includes rhythmic changes in the overall effects and in the effectiveness of some drugs. Clinical chronopharmacology is useful for solving problems of drug optimization, i.e. enhancing the desired efficiency of a drug and reducing its undesired effects. Circadian rhythms can be demonstrated in various effects of drugs on sleep, anaesthesia and related processes. For example, in the rat the duration of sleep induced by substances such as pentobarbital, hexobarbital, Althesin (alphaxadone and alphadoline in castor oil) is circadian system stage-dependent. Time-dependent changes of liver enzymes (e.g. hexobarbital oxidase) play a role in these circadian rhythms. The clinical chronopharmacokinetics of benzodiazepines have been documented in man. Chronopharmacologic methods can be used to study desired and undesired hypnotic effects of substances. Such is the case of new antihistamines (anti-H1), which do not induce sleepiness, in either acute or chronic administration. Pertinent also is the problem of intolerance to shift-work. Intolerant shift-workers are subject to internal desynchronization between at least two rhythms (e.g. activity-rest cycle and body temperature). Clinically these workers suffer from sleep

Sensitivity to ethanol hypnosis and modulation of chloride channels does not cosegregate with pentobarbital sensitivity in HS mice.

PubMed

Allan, A M; Harris, R A

1989-06-01

Several findings suggest that barbiturates and alcohol produce their sedative effects through a common neural and possibly a common genetic mechanism. We tested this hypothesis by examining the correlation between ethanol and pentobarbital sedative effects in individual animals from a genetically heterogeneous population. The duration of pentobarbital-induced hypnosis (sleep-time) was unrelated to the sleep-time produced by ethanol in heterogeneous stock (HS) mice. Therefore, the present study also examined the effect of ethanol, pentobarbital, and flunitrazepam on muscimol-stimulated chloride flux into brain membranes prepared from HS mice selected for differences in pentobarbital- and ethanol-induced sleep-time. Brain membranes from mice selected for differences in ethanol sleep-time were differentially responsive to ethanol- and flunitrazepam-, but not to pentobarbital-induced augmentation of muscimol-stimulated chloride flux. No differences in augmentation of chloride flux by ethanol, pentobarbital, or flunitrazepam were found in membranes prepared from mice differentially sensitive to pentobarbital hypnosis. The ability of muscimol to stimulate chloride uptake was not related to ethanol or pentobarbital sensitivity. These findings suggest that sensitivity to ethanol is not likely to be genetically linked to pentobarbital sensitivity.

Positive effects of β-amyrin on pentobarbital-induced sleep in mice via GABAergic neurotransmitter system.

PubMed

Jeon, Se Jin; Park, Ho Jae; Gao, Qingtao; Lee, Hyung Eun; Park, Se Jin; Hong, Eunyoung; Jang, Dae Sik; Shin, Chan Young; Cheong, Jae Hoon; Ryu, Jong Hoon

2015-09-15

Sleep loss, insomnia, is considered a sign of imbalance of physiological rhythm, which can be used as pre-clinic diagnosis of various neuropsychiatric disorders. The aim of the present study is to understand the pharmacological actions of α- or β-amyrin, natural triterpene compound, on the sleep in mice. To analyze the sleeping behavior, we used the well-known pentobarbital-induced sleeping model after single administration of either α- or β-amyrin. The sleeping onset time was remarkably decreased and duration was prolonged by β-amyrin (1, 3, or 10mg/kg) but not by α-amyrin (1, 3, or 10mg/kg). These effects were significantly blocked by GABAA receptor antagonist, bicuculline. Moreover, β-amyrin increased brain GABA level compared to the vehicle administration. Overall, the present study suggests that β-amyrin would enhance the total sleeping behavior in pentobarbital-induced sleeping model via the activation of GABAergic neurotransmitter system through GABA content in the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

Central L-ornithine, but not polyamines, induces a hypnotic effect in neonatal chicks under acute stress.

PubMed

Kurauchi, Isao; Shigemi, Kazutaka; Kabuki, Yusuke; Hamasu, Kousuke; Yamane, Haruka; Aoki, Mami; Kawada, Yoko; Morishita, Koji; Denbow, D Michael; Furuse, Mitsuhiro

2010-02-01

To clarify whether L-ornithine and/or its metabolite involves sedative and hypnotic effects under social separation stress, the effects of intracerebroventricular (i.c.v.) injection of L-ornithine and polyamines (putrescine, spermidine and spermine) were compared in chicks. Birds were injected i.c.v. with 0.5 mumol of L-ornithine, putrescine, spermidine, spermine or saline (control). After injection, chicks were immediately separated from the flock and monitored for the number of distress vocalizations and various postures. L-Ornithine greatly attenuated the stress response and caused sedative and hypnotic effects. Among the polyamines, only putrescine attenuated distress vocalizations but did not induce sleep. In conclusion, the sedative and hypnotic effect of L-ornithine was mainly induced by L-ornithine itself, while the polyamines contributed to the sedative, but not hypnotic, effect under social separation stress.

21 CFR 522.1704 - Sodium pentobarbital injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium pentobarbital injection. 522.1704 Section... § 522.1704 Sodium pentobarbital injection. (a)(1) Specifications. Sodium pentobarbital injection is sterile and contains in each milliliter 64.8 milligrams of sodium pentobarbital. (2) Sponsor. See No...

Deepening Sleep by Hypnotic Suggestion

PubMed Central

Cordi, Maren J.; Schlarb, Angelika A.; Rasch, Björn

2014-01-01

Study Objectives: Slow wave sleep (SWS) plays a critical role in body restoration and promotes brain plasticity; however, it markedly declines across the lifespan. Despite its importance, effective tools to increase SWS are rare. Here we tested whether a hypnotic suggestion to “sleep deeper” extends the amount of SWS. Design: Within-subject, placebo-controlled crossover design. Setting: Sleep laboratory at the University of Zurich, Switzerland. Participants: Seventy healthy females 23.27 ± 3.17 y. Intervention: Participants listened to an auditory text with hypnotic suggestions or a control tape before napping for 90 min while high-density electroencephalography was recorded. Measurements and Results: After participants listened to the hypnotic suggestion to “sleep deeper” subsequent SWS was increased by 81% and time spent awake was reduced by 67% (with the amount of SWS or wake in the control condition set to 100%). Other sleep stages remained unaffected. Additionally, slow wave activity was significantly enhanced after hypnotic suggestions. During the hypnotic tape, parietal theta power increases predicted the hypnosis-induced extension of SWS. Additional experiments confirmed that the beneficial effect of hypnotic suggestions on SWS was specific to the hypnotic suggestion and did not occur in low suggestible participants. Conclusions: Our results demonstrate the effectiveness of hypnotic suggestions to specifically increase the amount and duration of slow wave sleep (SWS) in a midday nap using objective measures of sleep in young, healthy, suggestible females. Hypnotic suggestions might be a successful tool with a lower risk of adverse side effects than pharmacological treatments to extend SWS also in clinical and elderly populations. Citation: Cordi MJ, Schlarb AA, Rasch B. Deepening sleep by hypnotic suggestion. SLEEP 2014;37(6):1143-1152. PMID:24882909

Tricaine (MS-222) is a safe anesthetic compound compared to benzocaine and pentobarbital to induce anesthesia in leopard frogs (Rana pipiens).

PubMed

Cakir, Yavuz; Strauch, Stephen M

2005-01-01

Tricaine (MS-222) is used commonly for sedation, immobilization, and anesthesia of poikilothermic animals. The anesthetic efficacy of different concentrations of MS-222 was compared to benzocaine and pentobarbital on the physiological changes, heart rate and ECG (electrocardiogram) parameters in the leopard frog, Rana pipiens. Loss of righting reflex (RR), loss of pain response (NR = nociceptor response) and recovery time were measured. Heart rate and ECG parameters were also tested before and during anesthesia. The time to loss of RR and NR decreased while recovery time markedly increased with the increasing concentration of MS-222. Benzocaine at 200 mg/l induced a rapid anesthesia, but all frogs needed resuscitation. Pentobarbital at 300 mg/l induced a slow anesthesia, however, all of the frogs also needed resuscitation. All anesthetics at the mentioned concentrations decreased heart rate significantly as well as altered the ECG parameters. All anesthetics prolonged the Q-T interval, and MS-222 at 800 mg/l and benzocaine at 200 mg/l were the most effective anesthetic concentrations in increasing the Q-T interval. Frogs anesthetized by benzocaine and pentobarbital and high concentrations of MS-222 required resuscitation due to hypoxia. Pentobarbital and benzocaine seem to be very effective compounds, but their safety margins are narrow because of ventilatory failure. Therefore, MS-222 at a concentration of 200 mg/l or less is highly recommended for leopard frogs because prolonged recovery, high mortality rate and significant ECG changes are observed with higher concentrations of MS-222.

Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

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

Olson, J.J.; Friedman, R.; Orr, K.

1990-05-01

Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose,more » a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.« less

Skin reactions to histamine of healthy subjects after hypnotically induced emotions of sadness, anger, and happiness.

PubMed

Zachariae, R; Jørgensen, M M; Egekvist, H; Bjerring, P

2001-08-01

The severity of symptoms in asthma and other hypersensitivity-related disorders has been associated with changes in mood but little is known about the mechanisms possibly mediating such a relationship. The purpose of this study was to examine the influence of mood on skin reactivity to histamine by comparing the effects of hypnotically induced emotions on flare and wheal reactions to cutaneous histamine prick tests. Fifteen highly hypnotically susceptible volunteers had their cutaneous reactivity to histamine measured before hypnosis at 1, 2, 3, 4, 5, 10, and 15 min after the histamine prick. These measurements were repeated under three hypnotically induced emotions of sadness, anger, and happiness presented in a counterbalanced order. Skin reactions were measured as change in histamine flare and wheal area in mm2 per minute. The increase in flare reaction in the time interval from 1 to 3 min during happiness and anger was significantly smaller than flare reactions during sadness (P<0.05). No effect of emotion was found for wheal reactions. Hypnotic susceptibility scores were associated with increased flare reactions at baseline (r=0.56; P<0.05) and during the condition of happiness (r=0.56; P<0.05). Our results agree with previous studies showing mood to be a predictor of cutaneous immediate-type hypersensitivity and histamine skin reactions. The results are also in concordance with earlier findings of an association between hypnotic susceptibility and increased reactivity to an allergen.

Is high hypnotic suggestibility necessary for successful hypnotic pain intervention?

PubMed

Milling, Leonard S

2008-04-01

Hypnotic suggestibility is a trait-like, individual difference variable reflecting the general tendency to respond to hypnosis and hypnotic suggestions. Research with standardized measures of hypnotic suggestibility has demonstrated that there are substantial individual differences in this variable. Higher suggestibility has been found to be associated with greater relief from hypnotic pain interventions. Although individuals in the high suggestibility range show the strongest response to hypnotic analgesia, people of medium suggestibility, who represent approximately one third of the population, also have been found to obtain significant relief from hypnosis. Thus, high hypnotic suggestibility is not necessary for successful hypnotic pain intervention. However, the available evidence does not support the efficacy of hypnotic pain interventions for people who fall in the low hypnotic suggestibility range. However, some studies suggest that these individuals may benefit from imaginative analgesia suggestions, or suggestions for pain reduction that are delivered while the person is not in hypnosis.

The effects of pentobarbital, ketamine-pentobarbital and ketamine-xylazine anesthesia in a rat myocardial ischemic reperfusion injury model.

PubMed

Shekarforoush, Shahnaz; Fatahi, Zahra; Safari, Fatemeh

2016-06-01

To achieve reliable experimental data, the side-effects of anesthetics should be eliminated. Since anesthetics exert a variety of effects on hemodynamic data and incidence of arrhythmias, the selection of anesthetic agents in a myocardial ischemic reperfusion injury model is very important. The present study was performed to compare hemodynamic variables, the incidence of ventricular arrhythmias, and infarct size during 30 min of ischemia and 120 min of reperfusion in rats using pentobarbital, ketamine-pentobarbital or ketamine-xylazine anaesthesia. A total of 30 rats were randomly divided into three groups. In group P, pentobarbital (60 mg/kg, intraperitoneally [IP]) was used solely; in group K-P, ketamine and pentobarbital (50 and 30 mg/kg, respectively, IP) were used in combination; and in group K-X, ketamine and xylazine (75 and 5 mg/kg, respectively, IP) were also used in combination. Hemodynamic data and occurrence of ventricular arrhythmias were recorded throughout the experiments. The ischemic area was measured by triphenyltetrazolium chloride staining. The combination of ketamine-xylazine caused bradycardia and hypotension. The greatest reduction in mean arterial blood pressure during ischemia was in the P group. The most stability in hemodynamic parameters during ischemia and reperfusion was in the K-P group. The infarct size was significantly less in the K-X group. Whereas none of the rats anesthetized with ketamine-xylazine fibrillated during ischemia, ventricular fibrillation occurred in 57% of the animals anesthetized with pentobarbital or ketamine-pentobarbital. Because it offers the most stable hemodynamic parameters, it is concluded that the ketamine-pentobarbital anesthesia combination is the best anesthesia in a rat ischemia reperfusion injury model. © The Author(s) 2015.

Impulsivity, self-control, and hypnotic suggestibility.

PubMed

Ludwig, V U; Stelzel, C; Krutiak, H; Prunkl, C E; Steimke, R; Paschke, L M; Kathmann, N; Walter, H

2013-06-01

Hypnotic responding might be due to attenuated frontal lobe functioning after the hypnotic induction. Little is known about whether personality traits linked with frontal functioning are associated with responsiveness to hypnotic suggestions. We assessed whether hypnotic suggestibility is related to the traits of self-control and impulsivity in 154 participants who completed the Brief Self-Control Scale, the Self-Regulation Scale, the Barratt Impulsiveness Scale (BIS-11), and the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A). BIS-11 non-planning impulsivity correlated positively with HGSHS:A (Bonferroni-corrected). Furthermore, in the best model emerging from a stepwise multiple regression, both non-planning impulsivity and self-control positively predicted hypnotic suggestibility, and there was an interaction of BIS-11 motor impulsivity with gender. For men only, motor impulsivity tended to predict hypnotic suggestibility. Hypnotic suggestibility is associated with personality traits linked with frontal functioning, and hypnotic responding in men and women might differ. Copyright © 2013 Elsevier Inc. All rights reserved.

Pavlovian control of cross-tolerance between pentobarbital and ethanol.

PubMed

Cappell, H; Roach, C; Poulos, C X

1981-01-01

Tolerance to several effects of a number of drugs has been shown to depend on Pavlovian conditioning processes. Experiment I extended the compensatory conditioning model (Siegel 1975) to tolerance to the hypothermic effect of pentobarbital (30 mg/kg). In Experiment I, rats that acquired hypothermic tolerance in one environment did not display tolerance when tested in an environment not previously associated with drug administration. In Experiment II, rats were made tolerant to the hypothermic effect of pentobarbital (30 mg/kg) and tested for cross-tolerance to ethanol (2.5 g/kg). Cross-tolerance was observed, but it was significantly reduced if the test was in an environment different from the one in which tolerance to pentobarbital was originally acquired. Thus, the compensatory conditioning model accounts for at least part of the tolerance and cross-tolerance to the thermic effects of alcohol and pentobarbital. The physiological processes in the CNS underlying tolerance and cross-tolerance for these drugs, therefore, are controlled by associative processes.

Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

PubMed Central

Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

2004-01-01

Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (P<0.01). Less potent nootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (P<0.001). Piracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

Suggestibility, expectancy, trance state effects, and hypnotic depth: I. Implications for understanding hypnotism.

PubMed

Pekala, Ronald J; Kumar, V K; Maurer, Ronald; Elliott-Carter, Nancy; Moon, Edward; Mullen, Karen

2010-04-01

This paper reviews the relationships between trance or altered state effects, suggestibility, and expectancy as these concepts are defined in the theorizing of Weitzenhoffer (2002), Holroyd (2003), Kirsch (1991), and others, for the purpose of demonstrating how these concepts can be assessed with the PCI-HAP (Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure; Pekala, 1995a, b). In addition, how the aforementioned variables may relate to the nature of hypnosis/hypnotism as a function of self-reported hypnotic depth are discussed, along with how the PCI-HAP may be used as a means to measure hypnotic responsivity from a more phenomenological state perspective, in contrast to more traditional behavioral trait assessment instruments like the Harvard, the Stanford C, or the HIP. A follow-up paper (Pekala, Kumar, Maurer, Elliott-Carter, Moon, & Mullen, 2010) will present research data on the PCI-HAP model and how this model can be useful for better understanding hypnotism.

Pentobarbital quantitation using EMIT serum barbiturate assay reagents: application to monitoring of high-dose pentobarbital therapy.

PubMed

Pape, B E; Cary, P L; Clay, L C; Godolphin, W

1983-01-01

Pentobarbital serum concentrations associated with a high-dose therapeutic regimen were determined using EMIT immunoassay reagents. Replicate analyses of serum controls resulted in a within-assay coefficient of variation of 5.0% and a between-assay coefficient of variation of 10%. Regression analysis of 44 serum samples analyzed by this technique (y) and a reference procedure (x) were y = 0.98x + 3.6 (r = 0.98; x = ultraviolet spectroscopy) and y = 1.04x + 2.4 (r = 0.96; x = high-performance liquid chromatography). Clinical evaluation of the results indicates the immunoassay is sufficiently sensitive and selective for pentobarbital to allow accurate quantitation within the therapeutic range associated with high-dose therapy.

Responding to hypnotic and nonhypnotic suggestions: performance standards, imaginative suggestibility, and response expectancies.

PubMed

Meyer, Eric C; Lynn, Steven Jay

2011-07-01

This study examined the relative impact of hypnotic inductions and several other variables on hypnotic and nonhypnotic responsiveness to imaginative suggestions. The authors examined how imaginative suggestibility, response expectancies, motivation to respond to suggestions, and hypnotist-induced performance standards affected participants' responses to both hypnotic and nonhypnotic suggestions and their suggestion-related experiences. Suggestions were administered to 5 groups of participants using a test-retest design: (a) stringent performance standards; (b) lenient performance standards; (c) hypnosis test-retest; (d) no-hypnosis test-retest; and (e) no-hypnosis/hypnosis control. The authors found no support for the influence of a hypnotic induction or performance standards on responding to suggestions but found considerable support for the role of imaginative suggestibility and response expectancies in predicting responses to both hypnotic and nonhypnotic suggestions.

21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Chloral hydrate, pentobarbital, and magnesium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate sterile aqueous solution. (a) [Reserved] (b)(1) Specifications. Chloral hydrate, pentobarbital, and...

Brain Oscillations and Diurnal Variations in Hypnotic Responsiveness—A Commentary on “Diurnal Variations in Hypnotic Responsiveness: Is There an Optimal Time to be Hypnotized?”

PubMed Central

Jensen, Mark P.

2016-01-01

A recent study published in the International Journal of Clinical and Experimental Hypnosis reported an interesting diurnal pattern of hypnotic responsivity; specifically, the authors found higher hypnotic responsiveness in a large sample of undergraduates in the morning and early evening. However, they did not have an explanation for this pattern of findings. This pattern is consistent, however, with the theta hypothesis of hypnotic responsivity. Further examination of the associations between brain oscillations and response to hypnosis is needed to determine if specific oscillations such as theta (1) actually facilitate response to some hypnotic suggestions, (2) merely reflect hypnotic responding, or (3) reflect another factor that itself plays a causal role in response to hypnosis. PMID:26599996

Response expectancies, treatment credibility, and hypnotic suggestibility: mediator and moderator effects in hypnotic and cognitive-behavioral pain interventions.

PubMed

Milling, Leonard S; Shores, Jessica S; Coursen, Elizabeth L; Menario, Deanna J; Farris, Catherine D

2007-04-01

Several studies have shown that response expectancies are an important mechanism of popular psychological interventions for pain. However, there has been no research on whether response expectancies and treatment credibility independently mediate hypnotic and cognitive-behavioral pain interventions and whether the pattern of mediation is affected by experience with the interventions. Also, past research has indicated that hypnotic pain interventions may be moderated by hypnotic suggestibility. However, these studies have typically failed to measure the full range of suggestibility and have assessed pain reduction and suggestibility in the same experimental context, possibly inflating the association between these variables. To clarify the mediator role of response expectancies and treatment credibility, and the moderator role of hypnotic suggestibility in the hypnotic and cognitive-behavioral reduction of pain. Approximately 300 participants were assessed for suggestibility. Then, as part of an apparently unrelated experiment, 124 of these individuals received analogue cognitive-behavioral, hypnotic, or placebo control pain interventions. Response expectancies and credibility independently mediated treatment. The extent of mediation increased as participants gained more experience with the interventions. Suggestibility moderated treatment and was associated with relief only from the hypnotic intervention. Response expectancies and treatment credibility are unique mechanisms of hypnotic and cognitive-behavioral pain interventions. Hypnotic suggestibility predicts relief from hypnotic pain interventions and this association is not simply an artifact of measuring suggestibility and pain reduction in the same experimental context. The relationship between suggestibility and hypnotic pain reduction appears to be linear in nature.

Neurophysiological correlates of post-hypnotic alexia: a controlled study with Stroop test.

PubMed

Casiglia, Edoardo; Schiff, Sami; Facco, Enrico; Gabbana, Amos; Tikhonoff, Valérie; Schiavon, Laura; Bascelli, Anna; Avdia, Marsel; Tosello, Maria Teresa; Rossi, Augusto Mario; Haxhi Nasto, Hilda; Guidotti, Federica; Giacomello, Margherita; Amodio, Piero

2010-01-01

To clarify whether hypnotically-induced alexia was able to reduce the Stroop effect due to color/word interference, 12 volunteers (6 with high and 6 with low hypnotizability according to Stanford Hypnotic Susceptibility Scale Form C) underwent a Stroop test consisting of measuring, both in basal conditions and during post-hypnotic alexia, the reaction times (RT) at appearance of a colored word indicating a color. In basal conditions, RT were greater in case of incongruence. In highly hypnotizable participants, the interference was less pronounced during post-hypnotic alexia (-34%, p = 0.03). During alexia, late positive complexamplitude was also greater for congruent than incongruent conditions (p < 0.03), and cardiovascular response to stress was less pronounced as well. In participants showing low hypnotizability, no reduction of Stroop effect was detected during post-hypnotic alexia. Posthypnotic alexia is therefore a real and measurable phenomenon, capable of reducing the color-word interference and the haemodynamic effects of the Stroop test.

21 CFR 522.380 - Chloral hydrate, pentobarbital, and magnesium sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Chloral hydrate, pentobarbital, and magnesium... FORM NEW ANIMAL DRUGS § 522.380 Chloral hydrate, pentobarbital, and magnesium sulfate. (a) Specifications. Each milliliter of solution contains 42.5 milligrams (mg) of chloral hydrate, 8.86 mg of...

"On hypnotism" (1860) De l'hypnotisme.

PubMed

Robertson, Donald

2009-04-01

James Braid's last essay on hypnotism, the culmination of his work, summarized in a French translation for the Academy of Sciences, is published in English with comments. According to Braid, hypnotism is a psychological ("subjective") approach, fundamentally opposed to the paranormal claims and magnetic ("objective") theories of mesmerism. Hypnotism operates primarily by means of dominant ideas that the attention of the subject is fixated upon. The reversibility of hypnotic amnesia is taken as evidence of "double consciousness." However, over 90% of Braid's subjects did not exhibit this state of dissociation or any sleep-like responses but merely a sense of "reverie." Good subjects are as suggestible in the "waking" state as others are in hypnotism.

Hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis extracts in mice

PubMed Central

Hajhashemi, Valiollah; Safaei, Azadeh

2015-01-01

The aim of the present study was to evaluate hypnotic effect of Coriandrum sativum, Ziziphus jujuba, Lavandula angustifolia and Melissa officinalis hydroalcoholic extracts in mice to select the most effective ones for a combination formula. Three doses of the extracts (250, 500 and 1000 mg/kg of C. sativum and Z. jujuba and 200, 400 and 800 mg/kg of L. angustifolia and M. officinalis) were orally administered to male Swiss mice (20-25 g) and one hour later pentobarbital (50 mg/kg, i.p.) was injected to induce sleep. Onset of sleep and its duration were measured and compared. Control animals and reference group received vehicle (10 ml/kg, p.o.) and diazepam (3 mg/kg, i.p.), respectively. C. sativum and Z. jujuba failed to change sleep parameters. L. angustifolia at doses of 200, 400 and 800 mg/kg shortened sleep onset by 7.6%, 50% and 51.5% and prolonged sleep duration by 9.9%, 43.1% and 80.2%, respectively. Compared with control group the same doses of M. officinalis also decreased sleep onset by 24.7%, 27.5% and 51.2% and prolonged sleep duration by 37.9%, 68.7% and 131.7% respectively. Combinations of L. angustifolia and M. officinalis extracts showed additive effect and it is suggested that a preparation containing both extracts may be useful for insomnia. PMID:26779267

Brain correlates of hypnotic paralysis-a resting-state fMRI study.

PubMed

Pyka, M; Burgmer, M; Lenzen, T; Pioch, R; Dannlowski, U; Pfleiderer, B; Ewert, A W; Heuft, G; Arolt, V; Konrad, C

2011-06-15

Hypnotic paralysis has been used since the times of Charcot to study altered states of consciousness; however, the underlying neurobiological correlates are poorly understood. We investigated human brain function during hypnotic paralysis using resting-state functional magnetic resonance imaging (fMRI), focussing on two core regions of the default mode network and the representation of the paralysed hand in the primary motor cortex. Hypnotic suggestion induced an observable left-hand paralysis in 19 participants. Resting-state fMRI at 3T was performed in pseudo-randomised order awake and in the hypnotic condition. Functional connectivity analyses revealed increased connectivity of the precuneus with the right dorsolateral prefrontal cortex, angular gyrus, and a dorsal part of the precuneus. Functional connectivity of the medial frontal cortex and the primary motor cortex remained unchanged. Our results reveal that the precuneus plays a pivotal role during maintenance of an altered state of consciousness. The increased coupling of selective cortical areas with the precuneus supports the concept that hypnotic paralysis may be mediated by a modified representation of the self which impacts motor abilities. Copyright © 2011 Elsevier Inc. All rights reserved.

Recovery from dispositional and pharmacodynamic tolerance after chronic pentobarbital treatment.

PubMed

Okamoto, M; Rao, S N; Reyes, J; Rifkind, A B

1985-10-01

Recovery characteristics of dispositional and pharmacodynamic tolerances produced by chronic Na-pentobarbital treatment were studied. To study dispositional tolerance, the rate of disappearance of pentobarbital from blood was estimated by sequential blood sampling before and after chronic treatment and during 15 days of withdrawal after chronic treatment. Pentobarbital half-life values were compared with four representative cytochrome P-450-mediated hepatic microsomal mixed-function oxidase reactions: aminopyrine demethylase, benzo(a)pyrene hydroxylase, 7-ethoxycoumarin deethylase and 7-ethoxyresorufin deethylase and with the concentration of cytochrome P-450 in sequentially biopsied liver samples. Pharmacodynamic tolerance was evaluated by measuring the increase in pentobarbital blood concentration required to produce predetermined central nervous system functional depression ratings. The recovery from dispositional tolerance was more rapid than the recovery from pharmacodynamic tolerance. Thus, whereas cytochrome P-450 levels and pentobarbital elimination rates were increased to close to twice pretreatment values by chronic treatment, by about 2 week post-withdrawal the values had normalized. In contrast, pharmacodynamic tolerance persisted after no residual dispositional tolerance remained. The neuronal functions most sensitive to barbiturate (i.e., sedation and loss of fine motor coordination) exhibited a greater degree of pharmacodynamic tolerance than other functions; hence the recovery of these neuronal functions took a longer period of time for their recovery. However, the rates of recovery of pharmacodynamic tolerance at all levels of central nervous system function seemed relatively constant indicating that there are uniform readaptation mechanisms for all the central nervous systems functions.

Mechanism of action of the hypnotic zolpidem in vivo

PubMed Central

Crestani, Florence; Martin, James R; Möhler, Hanns; Rudolph, Uwe

2000-01-01

Zolpidem is a widely used hypnotic agent acting at the GABAA receptor benzodiazepine site. On recombinant receptors, zolpidem displays a high affinity to α1-GABAA receptors, an intermediate affinity to α2- and α3-GABAA receptors and fails to bind to α5-GABAA receptors. However, it is not known which receptor subtype is essential for mediating the sedative-hypnotic action in vivo. Studying α1(H101R) mice, which possess zolpidem-insensitive α1-GABAA receptors, we show that the sedative action of zolpidem is exclusively mediated by α1-GABAA receptors. Similarly, the activity of zolpidem against pentylenetetrazole-induced tonic convulsions is also completely mediated by α1-GABAA receptors. These results establish that the sedative-hypnotic and anticonvulsant activities of zolpidem are due to its action on α1-GABAA receptors and not on α2- or α3-GABAA receptors. PMID:11090095

21 CFR 522.2444b - Sodium thiopental, sodium pentobarbital for injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Sodium thiopental, sodium pentobarbital for... FORM NEW ANIMAL DRUGS § 522.2444b Sodium thiopental, sodium pentobarbital for injection. (a) Specifications. Each gram of the drug contains 750 milligrams of sodium thiopental and 250 milligrams of sodium...

21 CFR 522.2444b - Sodium thiopental, sodium pentobarbital for injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Sodium thiopental, sodium pentobarbital for... FORM NEW ANIMAL DRUGS § 522.2444b Sodium thiopental, sodium pentobarbital for injection. (a) Specifications. Each gram of the drug contains 750 milligrams of sodium thiopental and 250 milligrams of sodium...

Non Benzodiazepines Hypnotics: Another Way to Induce Sleep

DTIC Science & Technology

2000-03-01

caused by disruption environment and we feel intuitively that it must fulfil of circadian rhythm . Another factor that disrupts some restorative function...Many circadian rhythms are circadian rhythms is the conduct of nocturnal operations, linked tightly to our sleep/wake cycle. An adequate a current...The perfect hypnotic should act brain activity and metabolism (38). rapidly, have a short duration of action, not lead to Arousal and wakefulness seem

Can motor imagery and hypnotic susceptibility explain Conversion Disorder with motor symptoms?

PubMed

Srzich, Alexander J; Byblow, Winston D; Stinear, James W; Cirillo, John; Anson, J Greg

2016-08-01

Marked distortions in sense of agency can be induced by hypnosis in susceptible individuals, including alterations in subjective awareness of movement initiation and control. These distortions, with associated disability, are similar to those experienced with Conversion Disorder (CD), an observation that has led to the hypothesis that hypnosis and CD share causal mechanisms. The purpose of this review is to explore the relationships among motor imagery (MI), hypnotic susceptibility, and CD, then to propose how MI ability may contribute to hypnotic responding and CD. Studies employing subjective assessments of mental imagery have found little association between imagery abilities and hypnotic susceptibility. A positive association between imagery abilities and hypnotic susceptibility becomes apparent when objective measures of imagery ability are employed. A candidate mechanism to explain motor responses during hypnosis is kinaesthetic MI, which engages a strategy that involves proprioception or the "feel" of movement when no movement occurs. Motor suppression imagery (MSI), a strategy involving inhibition of movement, may provide an alternate objective measurable phenomenon that underlies both hypnotic susceptibility and CD. Evidence to date supports the idea that there may be a positive association between kinaesthetic MI ability and hypnotic susceptibility. Additional evidence supports a positive association between hypnotic susceptibility and CD. Disturbances in kinaesthetic MI performance in CD patients indicate that MI mechanisms may also underlie CD symptoms. Further investigation of the above relationships is warranted to explain these phenomena, and establish theoretical explanations underlying sense of agency. Copyright © 2016. Published by Elsevier Ltd.

Discriminative-stimulus effects of zolpidem, triazolam, pentobarbital, and caffeine in zolpidem-trained humans.

PubMed

Rush, C R; Baker, R W; Rowlett, J K

2000-02-01

Six non-drug-abusing humans were trained to discriminate 15 mg zolpidem in the present experiment. After participants acquired discrimination, a range of doses of zolpidem (2.5-15.0 mg), triazolam (0.0625-0.3750 mg), pentobarbital (25-150 mg), caffeine (100-600 mg), and placebo were tested to determine whether they shared discriminative-stimulus effects with 15 mg zolpidem. The participant-rated and performance-impairing effects of zolpidem, triazolam, pentobarbital, and caffeine were assessed concurrently. Triazolam and pentobarbital dose dependently increased zolpidem-appropriate responding. Caffeine occasioned low levels of zolpidem-appropriate responding. Zolpidem, triazolam, and pentobarbital, but not caffeine, generally produced a similar constellation of participant-rated drug effects (e.g., increased scores for the Pentobarbital, Chlorpromazine, and Alcohol Group subscale on the Addiction Research Center Inventory) and dose dependently impaired performance. These results suggest that humans can reliably discriminate zolpidem. Despite its unique benzodiazepine-receptor binding profile, the discriminative-stimulus, participant-rated, and performance-impairing effects of zolpidem are similar to those of the barbiturates and benzodiazepines.

Sleep Restriction Therapy and Hypnotic Withdrawal versus Sleep Hygiene Education in Hypnotic Using Patients with Insomnia

PubMed Central

Taylor, Daniel J.; Schmidt-Nowara, Wolfgang; Jessop, Carol A.; Ahearn, John

2010-01-01

Study Objectives: Insomnia is a common problem that affects 9% to 15% of the population chronically. The primary objective of this study was to demonstrate that 8 weekly sessions of sleep restriction therapy of insomnia combined with hypnotic reduction instructions following a single session of sleep hygiene education would result in greater improvements in sleep and hypnotic use than sleep hygiene education alone. Methods: Forty-six men and women were recruited from a sleep medicine practice and randomly assigned to sleep hygiene education plus 8 weeks of sleep restriction and hypnotic withdrawal (SR+HW; n = 24), or a sleep hygiene education alone (SHE; n = 22) condition. Pre-randomization, all patients received a single session of instruction in good sleep habits (sleep hygiene education). Results: The SR+HW condition had greater improvements in hypnotic medication usage, sleep onset latency, morning wake time, sleep efficiency, and wake time after sleep onset (trend), than the SHE condition. Continued improvement was seen in TST in the SR+HW group at 6-month follow-up, and gains on all other variables were maintained at 6- and 12-month follow-up. Conclusions: These results provide evidence that more intensive treatment of insomnia (i.e., 8 sessions of SR+HW plus hypnotic withdrawal instructions) results in better outcomes than SHE alone. Citation: Taylor DJ; Schmidt-Nowara W; Jessop CA; Ahearn J. Sleep restriction therapy and hypnotic withdrawal versus sleep hygiene education in hypnotic using patients with insomnia. J Clin Sleep Med 2010;6(2):169-175. PMID:20411695

Hypnotic Approaches for Chronic Pain Management

PubMed Central

Jensen, Mark P.; Patterson, David R.

2015-01-01

The empirical support for hypnosis for chronic pain management has flourished over the past two decades. Clinical trials show that hypnosis is effective for reducing chronic pain, although outcomes vary between individuals. The findings from these clinical trials also show that hypnotic treatments have a number of positive effects beyond pain control. Neurophysiological studies reveal that hypnotic analgesia has clear effects on brain and spinal-cord functioning that differ as a function of the specific hypnotic suggestions made, providing further evidence for the specific effects of hypnosis. The research results have important implications for how clinicians can help their clients experience maximum benefits from hypnosis and treatments that include hypnotic components. PMID:24547802

Suicide by Fatal Pentobarbital Intoxication in Ontario, Canada, from 2012 to 2015.

PubMed

Solbeck, Patricia; Snowdon, Victoria; Rajagopalan, Ashwyn; Jhirad, Reuven

2018-05-24

A fatal concentration of pentobarbital found in a coroner's case where the history had not indicated use of this drug prompted a review of fatalities in Ontario from 2012 to 2015. Coroner's case files, including police and toxicology reports, were reviewed in twenty deaths, in which pentobarbital was identified as the primary cause of death. In all of the deaths (11 females, 9 males), the blood concentration of pentobarbital was greater than 10 mg/L. There were three to eight deaths per year and each was classified as suicide. In 11 cases, there was clear evidence that the drug was purchased over the internet from Mexico or China and imported into Canada. In four cases, it appears that the pentobarbital was labeled as a different, innocuous chemical to facilitate crossing the border without scrutiny. The findings underscore the value of a thorough scene investigation, including details of evidence that may be considered unrelated. © 2018 American Academy of Forensic Sciences.

Hypnotic suggestibility predicts the magnitude of the imaginative word blindness suggestion effect in a non-hypnotic context.

PubMed

Parris, Benjamin A; Dienes, Zoltan

2013-09-01

The present study investigated how the magnitude the word blindness suggestion effect on Stroop interference depended on hypnotic suggestibility when given as an imaginative suggestion (i.e. not post-hypnotic suggestion) and under conditions in which hypnosis was not mentioned. Hypnotic suggestibility is shown to be a significant predictor of the magnitude of the imaginative word blindness suggestion effect under these conditions. This is therefore the first study to show a linear relationship between the imaginative word blindness suggestion effect and hypnotic suggestibility across the whole hypnotizability spectrum. The results replicate previous findings showing that highs respond to the word blindness suggestion to a greater extent than lows but extend previous work by showing that the advantage for those higher on the hypnotizability spectrum occurs even in a non-hypnotic context. Negative attitudes about hypnosis may not explain the failure to observe similar effects of the word blindness suggestion in less hypnotizable individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

A tryptic hydrolysate from bovine milk αs1-casein enhances pentobarbital-induced sleep in mice via the GABAA receptor.

PubMed

Dela Peña, Irene Joy I; Kim, Hee Jin; de la Peña, June Bryan; Kim, Mikyung; Botanas, Chrislean Jun; You, Kyung Yi; Woo, Taeseon; Lee, Yong Soo; Jung, Jae-Chul; Kim, Kyung-Mi; Cheong, Jae Hoon

2016-10-15

Studies have shown that enzymatic hydrolysis of casein, the primary protein component of cow's milk, produces peptides with various biological activities, and some of these peptides may have sleep-promoting effects. In the present study, we evaluated the sedative and sleep-promoting effects of bovine αS1-casein tryptic hydrolysate (CH), containing a decapeptide αS1-casein known as alpha-casozepine. CH was orally administered to ICR mice at various concentrations (75, 150, 300, or 500mg/kg). An hour after administration, assessment of its sedative (open-field and rota-rod tests) and sleep-potentiating effects (pentobarbital-induced sleeping test and EEG monitoring) were conducted. Although a trend can be observed, CH treatment did not significantly alter the spontaneous locomotor activity and motor function of mice in the open-field and rota-rod tests. On the other hand, CH (150mg/kg, respectively) enhanced the sleep induced by pentobarbital sodium in mice. It also promoted slow-wave (delta) EEG activity in rats; a pattern indicative of sleep or relaxation. These behavioral results indicate that CH has sleep-promoting effects, but no or has minimal sedative effects. To elucidate the probable mechanism behind the effects of CH, we examined its action on intracellular chloride ion influx in cultured human neuroblastoma cells. CH dose-dependently increased chloride ion influx, which was blocked by co-administration of bicuculline, a competitive GABAA receptor antagonist. Taken together, the results of the present study suggest that CH has sleep-promoting properties which are probably mediated through the GABAA receptor-chloride ion channel complex. Copyright © 2016 Elsevier B.V. All rights reserved.

What Can a Hypnotic Induction Do?

PubMed

Woody, Erik; Sadler, Pamela

2016-10-01

In contrast to how recent definitions of hypnosis describe the induction, a work-sample perspective is advocated that characterizes the induction as an initial, stage-setting phase encompassing everything in a hypnotic session up to the first hypnotic suggestion of particular relevance to the therapeutic or research goals at hand. Four major ways are then discussed in which the induction could affect subsequent hypnotic responses: It may provide information about how subsequent behaviors are to be enacted; it may provide cues about the nature of the interpersonal interaction to be expected in hypnosis; it may provide meta-suggestions, defined as suggestive statements intended to enhance responses to subsequent hypnotic suggestions; and it may provide a clear transition to help allow new behaviors and experiences to emerge. Several ideas for future research are advanced, such as mapping hypnosis style onto the interpersonal circumplex, evaluating whether attentional-state changes measured at the end of the induction actually mediate subsequent hypnotic responsiveness, and systematically examining the impact of ritual-like aspects of inductions.

Classroom Seating and Hypnotic Susceptibility.

ERIC Educational Resources Information Center

Sackeim, Harold A.; And Others

1979-01-01

The purpose of this study was to examine whether people who differ in behavioral and self-report measures of lateralized seating preferences also differ in hypnotic susceptibility. Only right-handed subjects were used, and the associations between hypnotic susceptibility and seating preference were examined separately for males and females.…

Hypnotics. Options to help your patients stop.

PubMed

Woodward, M

2000-10-01

There are a wide range of reasons why hypnotic agents may be started, but there is substantive evidence that they are often overused or misused. To review the reasons for stopping hypnotic agents, how to detect their use, how to facilitate the decision to withdraw and how to most effectively achieve withdrawal. In this article, the target group is using but not intentionally abusing hypnotic agents. In many cases it is possible for patients to permanently stop using hypnotic drugs. Withdrawal can generally be achieved in the community, using a gradual taper regimen, although it is often a difficult process and is more effective when the patient is aware of the health benefits to be gained from withdrawal. Once withdrawn, other approaches to maintain sleep need to be reinforced to reduce the risk of recommencing hypnotic therapy.

Hypnotic suggestibility, cognitive inhibition, and dissociation.

PubMed

Dienes, Zoltán; Brown, Elizabeth; Hutton, Sam; Kirsch, Irving; Mazzoni, Giuliana; Wright, Daniel B

2009-12-01

We examined two potential correlates of hypnotic suggestibility: dissociation and cognitive inhibition. Dissociation is the foundation of two of the major theories of hypnosis and other theories commonly postulate that hypnotic responding is a result of attentional abilities (including inhibition). Participants were administered the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C. Under the guise of an unrelated study, 180 of these participants also completed: a version of the Dissociative Experiences Scale that is normally distributed in non-clinical populations; a latent inhibition task, a spatial negative priming task, and a memory task designed to measure negative priming. The data ruled out even moderate correlations between hypnotic suggestibility and all the measures of dissociation and cognitive inhibition overall, though they also indicated gender differences. The results are a challenge for existing theories of hypnosis.

Age-dependent inhibition of pentobarbital sleeping time by ozone in mice and rats

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

Canada, A.T.; Calabrese, E.J.; Leonard, D.

1986-09-01

The effect of age on the metabolism of pentobarbital in mice and rats was investigated following exposure to 0.3 ppm of ozone for 3.75 hr. Young animals were 2.5 months of age and the mature were 18 months. The pentobarbital sleeping time was significantly prolonged following the ozone exposure in both the mice and rats when compared with an air control. No ozone effect on sleeping time was found in the young animals. The results indicate that there may be an age-related sensitivity to the occurrence of ozone-related inhibition of pentobarbital metabolism.

The impact of hypnotic suggestibility in clinical care settings.

PubMed

Montgomery, Guy H; Schnur, Julie B; David, Daniel

2011-07-01

Hypnotic suggestibility has been described as a powerful predictor of outcomes associated with hypnotic interventions. However, there have been no systematic approaches to quantifying this effect across the literature. This meta-analysis evaluates the magnitude of the effect of hypnotic suggestibility on hypnotic outcomes in clinical settings. PsycINFO and PubMed were searched from their inception through July 2009. Thirty-four effects from 10 studies and 283 participants are reported. Results revealed a statistically significant overall effect size in the small to medium range (r = .24; 95% Confidence Interval = -0.28 to 0.75), indicating that greater hypnotic suggestibility led to greater effects of hypnosis interventions. Hypnotic suggestibility accounted for 6% of the variance in outcomes. Smaller sample size studies, use of the SHCS, and pediatric samples tended to result in larger effect sizes. The authors question the usefulness of assessing hypnotic suggestibility in clinical contexts.

The impact of hypnotic suggestibility in clinical care settings

PubMed Central

Montgomery, Guy H.; Schnur, Julie B.; David, Daniel

2013-01-01

Hypnotic suggestibility has been described as a powerful predictor of outcomes associated with hypnotic interventions. However, there have been no systematic approaches to quantifying this effect across the literature. The present meta-analysis evaluates the magnitude of the effect of hypnotic suggestibility on hypnotic outcomes in clinical settings. PsycINFO and PubMed were searched from their inception through July 2009. Thirty-four effects from ten studies and 283 participants are reported. Results revealed a statistically significant overall effect size in the small to medium range (r = 0.24; 95% Confidence Interval = −0.28 to 0.75), indicating that greater hypnotic suggestibility led to greater effects of hypnosis interventions. Hypnotic suggestibility accounted for 6% of the variance in outcomes. Smaller sample size studies, use of the SHCS, and pediatric samples tended to result in larger effect sizes. Results question the usefulness of assessing hypnotic suggestibility in clinical contexts. PMID:21644122

Some conditions of compliance and resistance among hypnotic subjects.

PubMed

Levitt, E E; Baker, E L; Fish, R C

1990-04-01

Five experimental approaches to the resolution of the century-old Bernheim/Janet dispute and the issue of involuntariness or coercion (the classical suggestion effect) are presented. Four experiments are reported that follow one of the approaches: attempts to induce hypnotic subjects to resist suggestions made in trance. The design is one in which a "resistance instructor" proposes a reward for the resisting subject. Tentative inferences from the results are that the classical suggestion effect is found with a small number of subjects; for a larger number of subjects there is no classical suggestion effect, and for many subjects the outcome is equivocal. Relational factors in the hypnotic dyad influence responsiveness in the subject, the effect being least for those whose susceptibility is high.

Hypnotic analgesia reduces brain responses to pain seen in others.

PubMed

Braboszcz, Claire; Brandao-Farinelli, Edith; Vuilleumier, Patrik

2017-08-29

Brain responses to pain experienced by oneself or seen in other people show consistent overlap in the pain processing network, particularly anterior insula, supporting the view that pain empathy partly relies on neural processes engaged by self-nociception. However, it remains unresolved whether changes in one's own pain sensation may affect empathic responding to others' pain. Here we show that inducing analgesia through hypnosis leads to decreased responses to both self and vicarious experience of pain. Activations in the right anterior insula and amygdala were markedly reduced when participants received painful thermal stimuli following hypnotic analgesia on their own hand, but also when they viewed pictures of others' hand in pain. Functional connectivity analysis indicated that this hypnotic modulation of pain responses was associated with differential recruitment of right prefrontal regions implicated in selective attention and inhibitory control. Our results provide novel support to the view that self-nociception is involved during empathy for pain, and demonstrate the possibility to use hypnotic procedures to modulate higher-level emotional and social processes.

Hypnosis, hypnotic suggestibility, memory, and involvement in films.

PubMed

Maxwell, Reed; Lynn, Steven Jay; Condon, Liam

2015-05-01

Our research extends studies that have examined the relation between hypnotic suggestibility and experiential involvement and the role of an hypnotic induction in enhancing experiential involvement (e.g., absorption) in engaging tasks. Researchers have reported increased involvement in reading (Baum & Lynn, 1981) and music-listening (Snodgrass & Lynn, 1989) tasks during hypnosis. We predicted a similar effect for film viewing: greater experiential involvement in an emotional (The Champ) versus a non-emotional (Scenes of Toronto) film. We tested 121 participants who completed measures of absorption and trait dissociation and the Harvard Group Scale of Hypnotic Susceptibility and then viewed the two films after either an hypnotic induction or a non-hypnotic task (i.e., anagrams). Experiential involvement varied as a function of hypnotic suggestibility and film clip. Highly suggestible participants reported more state depersonalization than less suggestible participants, and depersonalization was associated with negative affect; however, we observed no significant correlation between hypnotic suggestibility and trait dissociation. Although hypnosis had no effect on memory commission or omission errors, contrary to the hypothesis that hypnosis facilitates absorption in emotionally engaging tasks, the emotional film was associated with more commission and omission errors compared with the non-emotional film. Copyright © 2014 Elsevier Inc. All rights reserved.

Blood -brain barrier disruption was less under isoflurane than pentobarbital anesthesia via a PI3K/Akt pathway in early cerebral ischemia.

PubMed

Chi, Oak Z; Mellender, Scott J; Kiss, Geza K; Liu, Xia; Weiss, Harvey R

2017-05-01

One of the important factors altering the degree of blood-brain barrier (BBB) disruption in cerebral ischemia is the anesthetic used. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been reported to be involved in modulating BBB permeability and in isoflurane induced neuroprotection. This study was performed to compare the degree of BBB disruption in focal cerebral ischemia under isoflurane vs pentobarbital anesthesia and to determine whether inhibition of PI3K/Akt would affect the disruption in the early stage of focal cerebral ischemia. Permanent middle cerebral artery (MCA) occlusion was performed in rats under 1.4% isoflurane or pentobarbital (50mg/kg i.p.) anesthesia with controlled ventilation. In half of each group LY294002, which is a PI3K/Akt inhibitor, was applied on the ischemic cortex immediately after MCA occlusion. After one hour of MCA occlusion, the transfer coefficient (K i ) of 14 C-α-aminoisobutyric acid ( 14 C-AIB) was determined to quantify the degree of BBB disruption. MCA occlusion increased the K i both in the isoflurane and pentobarbital anesthetized rats. However, the value of K i was lower under isoflurane (11.5±6.0μL/g/min) than under pentobarbital (18.3±7.1μL/g/min) anesthesia. The K i of the contralateral cortex of the pentobarbital group was higher (+74%) than that of the isoflurane group. Application of LY294002 on the ischemic cortex increased the K i (+99%) only in the isoflurane group. The degree of BBB disruption by MCA occlusion was significantly lower under isoflurane than pentobarbital anesthesia in the early stage of cerebral ischemia. Our data demonstrated the importance of choice of anesthetics and suggest that PI3K/Akt signaling pathway plays a significant role in altering BBB disruption in cerebral ischemia during isoflurane but not during pentobarbital anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural and Functional Cerebral Correlates of Hypnotic Suggestibility

PubMed Central

Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo

2014-01-01

Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity. PMID:24671130

Structural and functional cerebral correlates of hypnotic suggestibility.

PubMed

Huber, Alexa; Lui, Fausta; Duzzi, Davide; Pagnoni, Giuseppe; Porro, Carlo Adolfo

2014-01-01

Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

[Morphological studies in different avian species on artefacts induced by euthanasia with T 61 " or Pentobarbital (Narcoren)].

PubMed

Kummerfeld, Norbert; Legler, Marko; Wohlsein, Peter; Kummerfeld, Maren

2012-01-01

In mammals (e. g. macaques, dogs, cats, rats, sheep) as well as in men (suicides) euthanasia performed by intravenous injection of T 61 leads to serious lesions in lung, kidney or/and liver (endothelial damage, hyperemia, oedema, necrosis). This is caused by the solvent dimethylformamide (DMF). In this study, in contrast, in different species of birds (e. g. blackbird, carrion crow, kestrel, common buzzard, homer pigeon, common wood pigeon, mallard duck) and various modes of applications and dosages T 61, 1.0-3.0 ml/kg body mass, did not induce comparable artefacts in tissues of internal organs in the narcotized animals. Microscopically, only hyperemia and oedema of lung, kidney and/or liver were found. However, milder but similar lesions were detected also in groups of birds euthanized by pentobarbital (200 mg/kg body mass) as well as in control groups (overdosed ketamine intramusculary, 100 mg/kg body mass, and rapid exsanguination). In conclusion, euthanasia of narcotized birds performed by intravenous or intracardial injections ofT 61 seemed to be suitable. The observed lesions could therefore not be interpreted as T61 induced artefacts.

Human exposures to pentobarbital-phenytoin combination veterinary drugs.

PubMed

Forrester, M B

2017-07-01

A combination of pentobarbital and phenytoin is used as a veterinary euthanasia drug. Because of its lethal effect, this study described pentobarbital-phenytoin combination veterinary drug human exposures reported to Texas poison centers during 2000-2015. Of 66 exposures, 73% involved female and 27% male patients. The distribution by patient age was 3% 0-5 years, 5% 6-19 years, 91% 20+ years, and 2% unknown. The most common routes were ocular (41%), ingestion (32%), injection (23%), and dermal (18%). The exposure reasons were unintentional (77%) and intentional (23%). The exposure site was the workplace (52%), patient's own residence (38%), health-care facility (2%), and other/unknown (9%). The management site was managed on site (48%), at/en route to health-care facility (45%), referred to health-care facility (5%), and other (2%). The medical outcomes were no effect (23%), minor effect (30%), moderate effect (8%), major effect (8%), not followed nontoxic (3%), not followed minimal effects (24%), unable to follow potentially toxic (2%), and unrelated (3%). The most common adverse effects were ocular irritation/pain (18%), drowsiness/lethargy (15%), and coma (9%). The most common treatments were dilution/irrigation (70%), intravenous fluids (21%), and oxygen (14%). This study found few pentobarbital-phenytoin combination veterinary drug exposures were reported to Texas poison centers during a 16-year period. Although meant to be administered intravenously, the most common exposure routes were ocular and ingestion. Many of the exposures appeared to be unintentional and occurred at the workplace.

Structural and functional correlates of hypnotic depth and suggestibility.

PubMed

McGeown, William Jonathan; Mazzoni, Giuliana; Vannucci, Manila; Venneri, Annalena

2015-02-28

This study explores whether self-reported depth of hypnosis and hypnotic suggestibility are associated with individual differences in neuroanatomy and/or levels of functional connectivity. Twenty-nine people varying in suggestibility were recruited and underwent structural, and after a hypnotic induction, functional magnetic resonance imaging at rest. We used voxel-based morphometry to assess the correlation of grey matter (GM) and white matter (WM) against the independent variables: depth of hypnosis, level of relaxation and hypnotic suggestibility. Functional networks identified with independent components analysis were regressed with the independent variables. Hypnotic depth ratings were positively correlated with GM volume in the frontal cortex and the anterior cingulate cortex (ACC). Hypnotic suggestibility was positively correlated with GM volume in the left temporal-occipital cortex. Relaxation ratings did not correlate significantly with GM volume and none of the independent variables correlated with regional WM volume measures. Self-reported deeper levels of hypnosis were associated with less connectivity within the anterior default mode network. Taken together, the results suggest that the greater GM volume in the medial frontal cortex and ACC, and lower connectivity in the DMN during hypnosis facilitate experiences of greater hypnotic depth. The patterns of results suggest that hypnotic depth and hypnotic suggestibility should not be considered synonyms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Comparison of propofol with pentobarbital/midazolam/fentanyl sedation for magnetic resonance imaging of the brain in children.

PubMed

Pershad, Jay; Wan, Jim; Anghelescu, Doralina L

2007-09-01

Propofol and pentobarbital, alone or combined with other agents, are frequently used to induce deep sedation in children for MRI. However, we are unaware of a previous comparison of these 2 agents as part of a randomized, controlled trial. We compared the recovery time of children after deep sedation with single-agent propofol with a pentobarbital-based regimen for MRI and considered additional variables of safety and efficacy. This prospective, randomized trial at a tertiary children's hospital enrolled 60 patients 1 to 17 years old who required intravenous sedation for elective cranial MRI. Patients were assigned randomly to receive a loading dose of propofol followed by continuous intravenous infusion of propofol or to receive sequential doses of midazolam, pentobarbital, and fentanyl until a modified Ramsay score of >4 was attained. A nurse who was blind to group assignment assessed discharge readiness (Aldrete score > 8) and administered a follow-up questionnaire. We compared recovery time, time to induction of sedation, total sedation time, quality of imaging, number of repeat-image sequences, adverse events, caregiver satisfaction, and time to return to presedation functional status. The groups were similar in age, gender, race, American Society of Anesthesiology physical status class, and frequency of cognitive impairment. No sedation failure or significant adverse events were observed. Propofol offered significantly shorter sedation induction time, recovery time, total sedation time, and time to return to baseline functional status. Caregiver satisfaction scores were also significantly higher in the patients in the propofol group. Propofol permits faster onset and recovery than, and comparable efficacy to, a pentobarbital/midazolam/fentanyl regimen for sedation of children for MRI.

Hypnotic suggestion: opportunities for cognitive neuroscience.

PubMed

Oakley, David A; Halligan, Peter W

2013-08-01

Hypnosis uses the powerful effects of attention and suggestion to produce, modify and enhance a broad range of subjectively compelling experiences and behaviours. For more than a century, hypnotic suggestion has been used successfully as an adjunctive procedure to treat a wide range of clinical conditions. More recently, hypnosis has attracted a growing interest from a cognitive neuroscience perspective. Recent studies using hypnotic suggestion show how manipulating subjective awareness in the laboratory can provide insights into brain mechanisms involved in attention, motor control, pain perception, beliefs and volition. Moreover, they indicate that hypnotic suggestion can create informative analogues of clinical conditions that may be useful for understanding these conditions and their treatments.

Mediation and moderation of psychological pain treatments: response expectancies and hypnotic suggestibility.

PubMed

Milling, Leonard S; Reardon, John M; Carosella, Gina M

2006-04-01

The mediator role of response expectancies and the moderator role of hypnotic suggestibility were evaluated in the analogue treatment of pain. Approximately 1,000 participants were assessed for hypnotic suggestibility. Later, as part of a seemingly unrelated experiment, 188 of these individuals were randomly assigned to distraction, cognitive-behavioral package, hypnotic cognitive-behavioral package, hypnotic analgesia suggestion, placebo control, or no-treatment control conditions. Response expectancies partially mediated the effects of treatment on pain. Hypnotic suggestibility moderated treatment and was associated with the relief produced only by the hypnotic interventions. The results suggest that response expectancies are an important mechanism of hypnotic and cognitive-behavioral pain treatments and that hypnotic suggestibility is a trait variable that predicts hypnotic responding across situations, including hypnosis-based pain interventions. Copyright 2006 APA

Procedure for detecting and confirming pentobarbital residues in dog food by gas chromatography/mass spectrometry.

PubMed

Adam, L A; Reeves, V B

1998-01-01

The method described detects and confirms presence of pentobarbital residues in dry, extruded feeds at concentrations of 5-20 ppb. Dried feed is ground to a uniform powder and shaken overnight in methanol. A portion of the methanolic extract is evaporated, and the residue is reconstituted in phosphate-buffered saline. The aqueous extract is cleaned with a solid-phase extraction cartridge designed to extract barbiturate residues from biological matrixes. Dimethyl sulfoxide, tetramethylammonium hydroxide, and iodomethane are added to derivatize pentobarbital, 1,3-Dimethyl-pentobarbital is then acidified with dilute hydrochloric acid and extracted with isooctane. The organic layer is transferred and evaporated under a stream of nitrogen. The residue is reconstituted in a small volume of ethyl acetate for analysis by gas chromatography/mass spectrometry. The limit of detection is approximately 0.7 ppb. The method was validated with pentobarbital-fortified feed samples containing high concentrations of meat and bone meal.

Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

PubMed

McCall, W Vaughn; Benca, Ruth M; Rosenquist, Peter B; Riley, Mary Anne; McCloud, Laryssa; Newman, Jill C; Case, Doug; Rumble, Meredith; Krystal, Andrew D

2017-01-01

Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has mandated that warnings regarding suicide be included in the prescribing information for hypnotic medications. The authors conducted a review of the evidence for and against the claim that hypnotics increase the risk of suicide. This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms "suicide" and "suicidal" with each of the modern FDA-approved hypnotics. The FDA web site was searched for postmarketing safety reviews, and the FDA was contacted with requests to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Reporting System. Epidemiological studies show that hypnotics are associated with an increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be suicidal. On the other hand, ongoing research is testing whether treatment of insomnia may reduce suicidality in adults with depression. The review findings indicate that hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess whether increases in suicidality result from CNS impairments from a given hypnotic medication or whether such medication decreases suicidality because of improvements in insomnia.

Hypnotic medications and suicide: risk, mechanisms, mitigation, and the FDA

PubMed Central

McCall, W. Vaughn; Benca, Ruth M.; Rosenquist, Peter B.; Riley, Mary Anne; McCloud, Laryssa; Newman, Jill C.; Case, Doug; Rumble, Meredith; Krystal, Andrew D.

2016-01-01

Objective Insomnia is associated with increased risk for suicide. The Food and Drug Administration (FDA) has warnings regarding suicide in the prescribing information of hypnotics. We conducted a review of the evidence for and against hypnotics increasing the risk of suicide. Method This review focused on modern, FDA-approved hypnotics, beginning with the introduction of benzodiazepines, limiting its findings to adults. PubMed and Web of Science were searched, crossing the terms ‘suicide’ and ‘suicidal’ with each of the modern FDA-approved hypnotics. The FDA website was searched for post-marketing safety reviews, and the FDA was contacted to provide detailed case reports for hypnotic-related suicide deaths reported through its Adverse Event Report system. Results The epidemiological studies show that hypnotics are associated with increased risk for suicide. However, none of these studies adequately controlled for depression or other psychiatric disorders that may be linked with insomnia. Suicide deaths have been reported from single-agent hypnotic overdoses. A separate concern is that benzodiazepine receptor agonist hypnotics can cause parasomnias, which in rare cases may lead to suicidal ideation or suicidal behavior in persons who were not known to be previously suicidal. On the other hand, ongoing research is testing whether treatment of insomnia might reduce suicidality in depressed adults. Conclusions This review indicates hypnotic medications are associated with suicidal ideation. Future studies should be designed to assess both types of possible effects: 1) an increase in suicidality due to central nervous system impairments from a given hypnotic medication; and 2) a decrease in suicidality due to improving insomnia. PMID:27609243

Differential Modulation of Ethanol-Induced Sedation and Hypnosis by Metabotropic Glutamate Receptor Antagonists in C57BL/6J Mice

PubMed Central

Sharko, Amanda C.; Hodge, Clyde W.

2008-01-01

Background Emerging evidence implicates metabotropic glutamate receptor (mGluR) function in the neurobiological effects of ethanol. The recent development of subtype specific mGluR antagonists has made it possible to examine the roles of specific mGluRs in biochemical and behavioral responses to ethanol. The purpose of the present study was to determine if mGluRs modulate the acute sedative-hypnotic properties of ethanol in mice. Methods C57BL / 6J mice were tested for locomotor activity (sedation) and duration of loss of the righting reflex (hypnosis) following acute systemic administration of ethanol alone or in combination with the mGluR5-selective antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), the mGluR1-selective antagonist, 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), or the mGluR2 / 3-selective antagonist (2S)-2-Amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495)). Results MPEP (10 and 30 mg / kg) significantly enhanced both the sedative and hypnotic effects of ethanol, while LY341495 (10 and 30 mg / kg) significantly reduced the sedative-hypnotic effects of ethanol. CPCCOEt had no effect at any concentration tested. Further loss of righting reflex experiments revealed that LY341495 (30 mg / kg) significantly reduced hypnosis induced by the gamma-aminobutyric acid type A (GABAA) positive modulators, pentobarbital (50 mg / kg) and midazolam (60 mg / kg), and the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine (150 mg / kg), while MPEP (30 mg / kg) only significantly enhanced the hypnotic properties of ketamine (150 mg / kg). Conclusions These findings suggest that specific subtypes of the metabotropic glutamate receptor differentially modulate the sedative-hypnotic properties of ethanol through separate mechanisms of action, potentially involving GABAA and NMDA receptors. PMID:18070246

GABAA receptor γ2 subunit knockdown mice have enhanced anxiety-like behavior but unaltered hypnotic response to benzodiazepines

PubMed Central

Chandra, Dev; Korpi, Esa R; Miralles, Celia P; De Blas, Angel L; Homanics, Gregg E

2005-01-01

Background Gamma-aminobutyric acid type A receptors (GABAA-Rs) are the major inhibitory receptors in the mammalian brain and are modulated by a number of sedative/hypnotic drugs including benzodiazepines and anesthetics. The significance of specific GABAA-Rs subunits with respect to behavior and in vivo drug responses is incompletely understood. The γ2 subunit is highly expressed throughout the brain. Global γ2 knockout mice are insensitive to the hypnotic effects of diazepam and die perinatally. Heterozygous γ2 global knockout mice are viable and have increased anxiety-like behaviors. To further investigate the role of the γ2 subunit in behavior and whole animal drug action, we used gene targeting to create a novel mouse line with attenuated γ2 expression, i.e., γ2 knockdown mice. Results Knockdown mice were created by inserting a neomycin resistance cassette into intron 8 of the γ2 gene. Knockdown mice, on average, showed a 65% reduction of γ2 subunit mRNA compared to controls; however γ2 gene expression was highly variable in these mice, ranging from 10–95% of normal. Immunohistochemical studies demonstrated that γ2 protein levels were also variably reduced. Pharmacological studies using autoradiography on frozen brain sections demonstrated that binding of the benzodiazepine site ligand Ro15-4513 was decreased in mutant mice compared to controls. Behaviorally, knockdown mice displayed enhanced anxiety-like behaviors on the elevated plus maze and forced novelty exploration tests. Surprisingly, mutant mice had an unaltered response to hypnotic doses of the benzodiazepine site ligands diazepam, midazolam and zolpidem as well as ethanol and pentobarbital. Lastly, we demonstrated that the γ2 knockdown mouse line can be used to create γ2 global knockout mice by crossing to a general deleter cre-expressing mouse line. Conclusion We conclude that: 1) insertion of a neomycin resistance gene into intron 8 of the γ2 gene variably reduced the amount of γ2

Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia dulcis Linn.

PubMed Central

Moniruzzaman, Md.; Atikur Rahman, Md.; Ferdous, Afia

2015-01-01

Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects. However, scientific information on SD regarding the neuropharmacological effect is limited. This study evaluated the sedative and hypnotic effect of the ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose, the whole plants of S. dulcis were extracted with ethanol following maceration process and tested for the presence of phytochemical constituents. The sedative and hypnotic activity were then investigated using hole cross, open field, hole-board, rota-rod, and thiopental sodium-induced sleeping time determination tests in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1 mg/kg was used as a reference drug in all the experiments. We found that EESD produced a significant dose-dependent inhibition of locomotor activity of mice both in hole cross and open field tests (P < 0.05). Besides, it also decreased rota-rod performances and the number of head dips in hole-board test. Furthermore, EESD significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Taken together, our study suggests that EESD may possess sedative principles with potent hypnotic properties. PMID:25861372

Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia dulcis Linn.

PubMed

Moniruzzaman, Md; Atikur Rahman, Md; Ferdous, Afia

2015-01-01

Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects. However, scientific information on SD regarding the neuropharmacological effect is limited. This study evaluated the sedative and hypnotic effect of the ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose, the whole plants of S. dulcis were extracted with ethanol following maceration process and tested for the presence of phytochemical constituents. The sedative and hypnotic activity were then investigated using hole cross, open field, hole-board, rota-rod, and thiopental sodium-induced sleeping time determination tests in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1 mg/kg was used as a reference drug in all the experiments. We found that EESD produced a significant dose-dependent inhibition of locomotor activity of mice both in hole cross and open field tests (P < 0.05). Besides, it also decreased rota-rod performances and the number of head dips in hole-board test. Furthermore, EESD significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Taken together, our study suggests that EESD may possess sedative principles with potent hypnotic properties.

In vivo proton MRS to quantify anesthetic effects of pentobarbital on cerebral metabolism and brain activity in rat.

PubMed

Du, Fei; Zhang, Yi; Iltis, Isabelle; Marjanska, Malgorzata; Zhu, Xiao-Hong; Henry, Pierre-Gilles; Chen, Wei

2009-12-01

To quantitatively investigate the effects of pentobarbital anesthesia on brain activity, brain metabolite concentrations and cerebral metabolic rate of glucose, in vivo proton MR spectra, and electroencephalography were measured in the rat brain with various doses of pentobarbital. The results show that (1) the resonances attributed to propylene glycol, a solvent in pentobarbital injection solution, can be robustly detected and quantified in the brain; (2) the concentration of most brain metabolites remained constant under the isoelectric state (silent electroencephalography) with a high dose of pentobarbital compared to mild isoflurane anesthesia condition, except for a reduction of 61% in the brain glucose level, which was associated with a 37% decrease in cerebral metabolic rate of glucose, suggesting a significant amount of "housekeeping" energy for maintaining brain cellular integrity under the isoelectric state; and (3) electroencephalography and cerebral metabolic activities were tightly coupled to the pentobarbital anesthesia depth and they can be indirectly quantified by the propylene glycol resonance signal at 1.13 ppm. This study indicates that in vivo proton MR spectroscopy can be used to measure changes in cerebral metabolite concentrations and cerebral metabolic rate of glucose under varied pentobarbital anesthesia states; moreover, the propylene glycol signal provides a sensitive biomarker for quantitatively monitoring these changes and anesthesia depth noninvasively. (c) 2009 Wiley-Liss, Inc.

Cognitive Expectancies for Hypnotic Use among Older Adult Veterans with Chronic Insomnia.

PubMed

Fung, Constance H; Martin, Jennifer L; Josephson, Karen; Fiorentino, Lavinia; Dzierzewski, Joseph M; Jouldjian, Stella; Song, Yeonsu; Rodriguez Tapia, Juan Carlos; Mitchell, Michael N; Alessi, Cathy A

2018-01-01

To examine relationships between cognitive expectancies about sleep and hypnotics and use of medications commonly used for insomnia (hypnotics). We analyzed baseline data from older veterans who met diagnostic criteria for insomnia and were enrolled in a trial comparing CBTI delivered by a supervised, sleep educator to an attention control condition (N = 159; 97% male, mean age 72 years). We classified individuals as hypnotic users (N = 23) vs. non-users (N = 135) based upon medication diaries. Associations between hypnotic status and Dysfunctional Beliefs and Attitudes about Sleep-16 (DBAS) total score (0-10, higher = worse) and two DBAS medication item scores (Item 1: "…better off taking a sleeping pill rather than having a poor night's sleep;" Item 2: "Medication… probably the only solution to sleeplessness"; 0-10, higher = worse) were examined in logistic regression models. Higher scores on the DBAS medication items (both odds ratios = 1.3; p-values < .001) were significantly associated with hypnotic use. DBAS-16 total score was not associated with hypnotic use. Cognitive expectancy (dysfunctional beliefs) about hypnotics was associated with hypnotic use in older adults with chronic insomnia disorder. Strategies that specifically target dysfunctional beliefs about hypnotics are needed and may impact hypnotic use in older adults.

Intracerebroventricular injection of L-serine analogs and derivatives induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks.

PubMed

Asechi, Mari; Tomonaga, Shozo; Tachibana, Tetsuya; Han, Li; Hayamizu, Kohsuke; Denbow, D Michael; Furuse, Mitsuhiro

2006-06-03

Four experiments were conducted to clarify the central functions of L-serine and its analogs on an acute stressful condition. Intracerebroventricular (i.c.v.) injection of L-serine (0.21, 0.42 and 0.84 micromol) attenuated stress responses in a dose-dependent fashion, as well as induced sleep, in Experiment 1. The effects of L- and D-serine in Experiment 2, those of L-serine, phosphoserine, acetylserine and L-cysteine in Experiment 3 and those of L-serine, glycine and lysophosphatidylserine in Experiment 4 were compared at an equimolar basis (0.84 micromol). D-Serine, proposed as an endogenous agonist of N-methyl-D-aspatate (NMDA) receptor, did not have sedative and hypnotic effects as observed with L-serine. In contrast, all the analogs and derivatives of L-serine had a sedative effect, although with a different manner in several behavioral markers of stress such as spontaneous activity and distress vocalizations. No significant changes in plasma corticosterone concentration were observed in any experiment. Taken together, the i.c.v. injection of L-serine analogs and its derivatives have sedative and hypnotic effects under an acute stressful condition, which does not involve the hypothalamic-pituitary-adrenal axis. In conclusion, L-serine may be effective in improving anxiety or sleep disorders induced by psychological stressor.

Effects of pentobarbital on plasma glucose and free fatty acids in the rat.

NASA Technical Reports Server (NTRS)

Furner, R. L.; Neville, E. D.; Talarico, K. S.; Feller, D. D.

1972-01-01

Hyperglycemia and hypolipemia were observed in rats after the injection of sodium pentobarbital. The observed changes were independent of whether the blood was collected by decapitation or by needle puncture of the aorta. The hyperglycemic response was caused by two factors including the stress of the injection per se and the pharmacological action of the drug. Hyperlipemia was observed at 5 min postinjection. However, pentobarbital decreased plasma free fatty acids by 15 min postinjection. Both the hyperglycemia and hypolipemia responses were dose dependent.

Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats.

PubMed

Shinomiya, Kazuaki; Inoue, Toshio; Utsu, Yoshiaki; Tokunaga, Shin; Masuoka, Takayoshi; Ohmori, Asae; Kamei, Chiaki

2005-05-01

In the present study, we investigated hypnotic activities of chamomile and passiflora extracts using sleep-disturbed model rats. A significant decrease in sleep latency was observed with chamomile extract at a dose of 300 mg/kg, while passiflora extract showed no effects on sleep latency even at a dose of 3000 mg/kg. No significant effects were observed with both herbal extracts on total times of wakefulness, non-rapid eye movement (non-REM) sleep and REM sleep. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3 mg/kg showed a significant antagonistic effect on the shortening in sleep latency induced by chamomile extract. No significant effects were observed with chamomile and passiflora extracts on delta activity during non-REM sleep. In conclusion, chamomile extract is a herb having benzodiazepine-like hypnotic activity.

An unusual case of relay pentobarbital toxicosis in a dog.

PubMed

Bischoff, Karyn; Jaeger, Robin; Ebel, Joseph G

2011-09-01

Sodium pentobarbital and phenytoin are common constituents of veterinary euthanasia solutions in the United States. Relay, or secondary, barbiturate toxicosis has been reported in carnivorous animals that have fed from the carcasses of euthanized livestock. This case report presents barbiturate toxicosis in a dog. A 2-year-old female spayed Australian shepherd presented comatose 2 h after ingesting an unknown substance on the beach. The material was retrieved from the stomach by gastric lavage and visually identified as fish or other animal tissue. The dog recovered with symptomatic and supportive therapy and was released on the third day of hospitalization. Tissue found on the beach near where the dog walked and a urine sample from the dog were analyzed by gas chromatography/mass spectrometry. Both samples were positive for pentobarbital and phenytoin. The tissue was consistent with mammalian blubber based on gross and histological examination. Three weeks previously, a juvenile humpback whale had stranded on the beach where the dog had ingested the unknown substance. The whale had been euthanized with a barbiturate solution, necropsied, and removed from the beach. It was not definitively determined that the pentobarbital-containing blubber ingested by the dog was from the euthanized whale, but that was the most likely source. Although attempts were made to remove the whale's remains from the beach, practical considerations made complete removal challenging, if not impossible.

Gene expression in the rat cerebral cortex: comparison of recovery sleep and hypnotic-induced sleep.

PubMed

Wisor, J P; Morairty, S R; Huynh, N T; Steininger, T L; Kilduff, T S

2006-08-11

Most hypnotic medications currently on the market target some aspect of GABAergic neurotransmission. Although all such compounds increase sleep, these drugs differentially affect the activity of the cerebral cortex as measured by the electroencephalogram. Whereas benzodiazepine medications such as triazolam tend to suppress slow wave activity in the cortex, the GABA(B) ligand gamma-hydroxybutyrate greatly enhances slow wave activity and the non-benzodiazepine, zolpidem, which binds to the omega1 site on the GABA(A) receptor/Cl(-) ionophore complex, is intermediate in this regard. Our previous studies have demonstrated that a small number of genes exhibit increased expression in the cerebral cortex of the mouse and rat during recovery sleep after sleep deprivation: egr-3, fra-2, grp78, grp94, ngfi-b, and nr4a3. Using these genes as a panel of biomarkers associated with sleep, we asked whether hypnotic medications induce similar molecular changes in the rat cerebral cortex to those observed when both sleep continuity and slow wave activity are enhanced during recovery sleep. We find that, although each drug increases the expression of a subset of genes in the panel of biomarkers, no drug fully replicates the molecular changes in the cortex associated with recovery sleep. Furthermore, high levels of slow wave activity in the cortex are correlated with increased expression of fra-2 whereas the expression of grp94 is correlated with body temperature. These results demonstrate that sleep-related changes in gene expression may be affected by physiological covariates of sleep and wakefulness rather than by vigilance state per se.

The Hypnotic Induction in the Broad Scheme of Hypnosis: A Sociocognitive Perspective.

PubMed

Lynn, Steven Jay; Maxwell, Reed; Green, Joseph P

2017-04-01

Researchers and clinicians typically divide hypnosis into two distinct parts: the induction and the suggestions that follow. We suggest that this distinction is arbitrary and artificial. Different definitions of hypnosis ascribe different roles to the hypnotic induction, yet none clearly specifies the mechanisms that mediate or moderate subjective and behavioral responses to hypnotic suggestions. Researchers have identified few if any differences in responding across diverse hypnotic inductions, and surprisingly little research has focused on the specific ingredients that optimize responsiveness. From a sociocognitive perspective, we consider the role of inductions in the broader scheme of hypnosis and suggest that there is no clear line of demarcation between prehypnotic information, the induction, suggestions, and other constituents of the hypnotic context. We describe research efforts to maximize responses to hypnotic suggestions, which encompass the induction and other aspects of the broader hypnotic framework, and conclude with a call for more research on inductions and suggestions to better understand their role within hypnotic interventions in research and clinical contexts.

Cross-evidence for hypnotic susceptibility through nonlinear measures on EEGs of non-hypnotized subjects

NASA Astrophysics Data System (ADS)

Chiarucci, Riccardo; Madeo, Dario; Loffredo, Maria I.; Castellani, Eleonora; Santarcangelo, Enrica L.; Mocenni, Chiara

2014-07-01

Assessment of hypnotic susceptibility is usually obtained through the application of psychological instruments. A satisfying classification obtained through quantitative measures is still missing, although it would be very useful for both diagnostic and clinical purposes. Aiming at investigating the relationship between the cortical brain activity and the hypnotic susceptibility level, we propose the combined use of two methodologies - Recurrence Quantification Analysis and Detrended Fluctuation Analysis - both inherited from nonlinear dynamics. Indicators obtained through the application of these techniques to EEG signals of individuals in their ordinary state of consciousness allowed us to obtain a clear discrimination between subjects with high and low susceptibility to hypnosis. Finally a neural network approach was used to perform classification analysis.

Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus).

PubMed

Zatroch, Katie K; Knight, Cameron G; Reimer, Julie N; Pang, Daniel S J

2017-02-21

The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume and IP euthanasia has been described as unreliable, with misinjections leading to variable success in ensuring a timely death. The aims of this study were to assess and improve efficacy and consistency of IP euthanasia. In a randomized, blinded study, 51 adult female Sprague-Dawley rats (170-495 g) received one of four treatments: low-dose low-volume (LL) IP pentobarbital (n = 13, 200 mg/kg pentobarbital), low-dose high-volume (LH) IP pentobarbital (n = 14, 200 mg/kg diluted 1:3 with phosphate buffered saline), high-dose high-volume (HH, n = 14, 800 mg/kg pentobarbital), or saline. Times to loss of righting reflex (LORR) and cessation of heartbeat (CHB) were recorded. To identify misinjections, necropsy examinations were performed on all rats. Video recordings of LL and HH groups were analyzed for pain-associated behaviors. Between-group comparisons were performed with 1-way ANOVA and Games-Howell post hoc tests. Variability in CHB was assessed by calculating the coefficient of variation (CV). The fastest euthanasia method (CHB) was HH (283.7 ± 38.0 s), compared with LL (485.8 ± 140.7 s, p = 0.002) and LH (347.7 ± 72.0 s, p = 0.039). Values for CV were: HH, 13.4%; LH, 20.7%; LL, 29.0%. LORR time was longest in LL (139.5 ± 29.6 s), compared with HH (111.6 ± 19.7 s, p = 0.046) and LH (104.2 ± 19.3 s, p = 0.01). Misinjections occurred in 17.0% (7/41) of euthanasia attempts. Pain-associated behavior incidence ranged from 36% (4/11, LL) to 46% (5/11, HH). These data illustrate refinement of the IP pentobarbital euthanasia technique. Both dose and volume contribute to speed of death, with a dose of 800 mg/kg (HH) being the most effective method. An increase in volume alone does not significantly reduce variability. The

Hidden Hypnotic Patterns: Implications for Counseling and Supervision.

ERIC Educational Resources Information Center

Gunnison, Hugh; Renick, T. F.

1985-01-01

Examines the hypothesis that subtle hypnotic patterns used by Milton H. Erickson are found in the person-centered approach to counseling of Carl Rogers. Points out that counselors and supervisors should be aware of the possible hypnotic elements in simple suggestions. Presents examples of counselor-client and supervisor-trainee dialogue to…

Effects of delta9-tetrahydrocannabinol and pentobarbital on a cortical response evoked during conditioning.

PubMed

Boyd, E S; Boyd, E H; Brown, L E

1976-05-05

A surface-negative wave, evoked by tone cues, appeared in monkey post-arcuate cortex as the monkey learned that the cue signaled the availability of reward. This evoked activity was depressed, concomitantly with changes in the animal's behavioral responding, by doses of delta9-tetrahydrocannabinol (delta9-THC) as low as 0.032 mg/kg and of pentobarbital as low as 4 mg/kg. Pentobarbital tended to increase the latency of the evoked wave, an effect not seen with delta9-THC.

Suggestibility, expectancy, trance state effects, and hypnotic depth: II. Assessment via the PCI-HAP.

PubMed

Pekala, Ronald J; Kumar, V K; Maurer, Ronald; Elliott-Carter, Nancy; Moon, Edward; Mullen, Karen

2010-04-01

This study sought to determine if self-reported hypnotic depth (srHD) could be predicted from the variables of the Phenomenology of Consciousness Inventory - Hypnotic Assessment Procedure (PCI-HAP) (Pekala, 1995a, 1995b; Pekala & Kumar, 2007; Pekala et al., 2010), assessing several of the processes theorized by researchers to be associated with hypnotism: trance (altered state effects), suggestibility, and expectancy. One hundred and eighty participants completed the PCI-HAP. Using regression analyses, srHD scores were predicted from the PCI-HAP pre-hypnotic and post-hypnotic assessment items, and several other variables. The results suggested that the srHD scores were found to be a function of imagoic suggestibility, expectancy (both estimated hypnotic depth and expected therapeutic efficacy), and trance state and eye catalepsy effects; effects that appear to be additive and not (statistically) interactive. The results support the theorizing of many investigators concerning the involvement of the aforementioned component processes with this particular aspect of hypnotism, the self-reported hypnotic depth score.

Marijuana Usage and Hypnotic Susceptibility

ERIC Educational Resources Information Center

Franzini, Louis R.; McDonald, Roy D.

1973-01-01

Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

Hypnotic responsiveness: expectancy, attitudes, fantasy proneness, absorption, and gender.

PubMed

Green, Joseph P; Lynn, Steven Jay

2011-01-01

This study examines the effect of providing information linking participants' attitudes toward hypnosis with later hypnotic performance. Using total scale scores from McConkey's Opinions About Hypnosis scale, as well as subscale scores, the authors found a weak association between attitudes and performance among 460 student participants; however, the correlation was unaffected by prehypnotic information specifically connecting attitudes and performance. A brief, 3-item measure of hypnotic expectancies generated the strongest correlation with hypnotic responsiveness. The authors also found that the association between fantasy proneness and hypnotizability was unaffected by the order of scale administration. Finally, the study highlighted gender differences across measures of fantasy proneness, absorption, expectancy, and hypnotizability.

Placebo versus "standard" hypnosis rationale: attitudes, expectancies, hypnotic responses, and experiences.

PubMed

Accardi, Michelle; Cleere, Colleen; Lynn, Steven Jay; Kirsch, Irving

2013-10-01

In this study participants were provided with either the standard rationale that accompanies the Harvard Group Scale of Hypnotic Susceptibility: A (Shor & Orne, 1962) or a rationale that presented hypnosis as a nondeceptive placebo, consistent with Kirsch's (1994) sociocognitive perspective of hypnosis. The effects of the placebo and standard rationales were highly comparable with respect to hypnotic attitudes; prehypnotic expectancies; objective, subjective, and involuntariness measures of hypnotic responding; as well as a variety of subjective experiences during hypnosis, as measured by the Phenomenology of Consciousness Inventory (Pekala, 1982). Differences among correlations were not evident when measures were compared across groups. However, indices of hypnotic responding were correlated with attitudes in the hypnosis but not the placebo condition, and, generally speaking, the link between subjective experiences during hypnosis and measures of hypnotic responding were more reliable in the placebo than the hypnosis group. Researcher findings are neutral with respect to providing support for altered state versus sociocognitive models of hypnosis.

Hypnotic Taper with or without Self-Help Treatment of Insomnia: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Belleville, Genevieve; Guay, Catherine; Guay, Bernard; Morin, Charles M.

2007-01-01

This study aimed to assess the efficacy of a minimal intervention focusing on hypnotic discontinuation and cognitive-behavioral treatment (CBT) for insomnia. Fifty-three adult chronic users of hypnotics were randomly assigned to an 8-week hypnotic taper program, used alone or combined with a self-help CBT. Weekly hypnotic use decreased in both…

DANGEROUS AND HYPNOTIC DRUG ACT

PubMed Central

Whelan, William M.

1961-01-01

It is unprofessional conduct within the meaning of the Medical Practice Act to prescribe a dangerous drug without either a medical examination by a physician or other medical indications. Dangerous and hypnotic drugs are specifically defined by both state and federal law and distribution is strictly regulated. A physician may administer to his own patients such amounts of dangerous drugs as are necessary for the immediate needs of the patient. The physician may obtain such needed amounts of these drugs by an order placed with a pharmacist marked “for administration to immediate needs of patients.” A licensed physician may also prescribe dangerous and hypnotic drugs for patients and such prescriptions may be refilled on the specific authorization of the physician. A physician who dispenses dangerous and hypnotic drugs to patients must obtain a hypnotic drug license; he must use specific purchase orders when purchasing; the drugs must be labeled in the manner provided by law; and all records of sale shall be open to inspection by authorized officers of the law and kept for three years. By the Principles of Medical Ethics physicians are bound to limit the source of their professional income to medical services actually rendered. Recent decisions of the Judicial Council answer questions concerning a physician's interest in a corporation which purchases, packages and sells medicines under a corporate name. Also answered are questions as to the measures that exist to prevent physicians from abusing the privilege of owning a pharmacy, and whether a physician can ethically rent space in a building owned by him to a pharmacist with a percentage of the income of the pharmacy as rental. The public welfare of California and the nation as determined by legislation strictly regulates the distribution of dangerous drugs. It is in the best interest of the medical profession and its patients that these laws be understood and carefully observed. PMID:13784776

Smoking Cessation: Uni-Modal and Multi-Modal Hypnotic and Non-Hypnotic Approaches.

ERIC Educational Resources Information Center

Habicht, Manuela H.

A survey of Queensland's population in 1993 determined that 24% of the adults were smokers. National data compiled in 1992 indicated that 72% of the drug-related deaths were related to tobacco use. In light of the need for effective smoking cessation approaches, a literature review was undertaken to determine the efficacy of hypnotic and…

Effect of hypnotic suggestion on the delayed-type hypersensitivity response.

PubMed

Locke, S E; Ransil, B J; Zachariae, R; Molay, F; Tollins, K; Covino, N A; Danforth, D

1994-07-06

To determine whether individuals selected for good general health, high hypnotizability, and the ability to alter skin temperature under hypnotic suggestion can influence the delayed-type hypersensitivity (DTH) response to varicella-zoster (VZ) antigen under hypnotic suggestion. A blinded clinical trial using a repeated measures design with subjects serving as their own controls. Subjects were randomly assigned to undergo a predetermined sequence of four different experimental conditions, occurring at weekly intervals, with each condition including VZ skin testing: (1) hypnosis with suggestions to enhance the DTH response to VZ antigen; (2) hypnosis with suggestions to suppress the DTH response; (3) hypnosis with suggestions for relaxation only; and (4) skin testing without hypnosis. A National Institutes of Health-supported clinical research center in a teaching hospital. A stratified sample of 24 ambulatory, healthy, highly hypnotizable, volunteer college students selected for their above-average ability to alter skin temperature after hypnotic suggestions and their positive baseline responses to VZ antigen. There were 11 males and 13 females with a mean +/- SD age of 22 +/- 6 years. The mean +/- SD hypnotizability score (Harvard Group Scale of Hypnotic Susceptibility) was 11 +/- 1. Intradermal skin testing with VZ antigen (Mantoux method) and hypnotic suggestion. Areas of induration of the DTH response measured at 24 and 48 hours after injection of antigen. The area of the DTH response was not affected by the experimental interventions. The area of erythema was likewise unaffected. Our subjects were unable to alter their DTH responses using hypnotic suggestion.

The Existence of a Hypnotic State Revealed by Eye Movements

PubMed Central

Kallio, Sakari; Hyönä, Jukka; Revonsuo, Antti; Sikka, Pilleriin; Nummenmaa, Lauri

2011-01-01

Hypnosis has had a long and controversial history in psychology, psychiatry and neurology, but the basic nature of hypnotic phenomena still remains unclear. Different theoretical approaches disagree as to whether or not hypnosis may involve an altered mental state. So far, a hypnotic state has never been convincingly demonstrated, if the criteria for the state are that it involves some objectively measurable and replicable behavioural or physiological phenomena that cannot be faked or simulated by non-hypnotized control subjects. We present a detailed case study of a highly hypnotizable subject who reliably shows a range of changes in both automatic and volitional eye movements when given a hypnotic induction. These changes correspond well with the phenomenon referred to as the “trance stare” in the hypnosis literature. Our results show that this ‘trance stare’ is associated with large and objective changes in the optokinetic reflex, the pupillary reflex and programming a saccade to a single target. Control subjects could not imitate these changes voluntarily. For the majority of people, hypnotic induction brings about states resembling normal focused attention or mental imagery. Our data nevertheless highlight that in some cases hypnosis may involve a special state, which qualitatively differs from the normal state of consciousness. PMID:22039474

Anxiolytic, sedative, and hypnotic activities of aqueous extract of Morinda citrifolia fruit

PubMed Central

Kannan, Sridharan; Manickam, Shanti; RajaMohammed, Meher Ali

2014-01-01

Morinda citrifolia (Indian mulberry or noni) fruit has been long used as a folk medicine for a wide range of health purposes as it is claimed to have analgesic, antiinflammatory, antioxidant, detoxifier, and cell-rejuvenator properties. A recent study has revealed central nervous system suppressant nature of its extract. Hence, the present study has evaluated the anxiolytic, sedative, and hypnotic effects of the aqueous extracts of Morinda citrifolia in rodents in comparison to diazepam. Anxiety was assessed by ‘Isolation-induced aggression’ model, sedation by ‘Spontaneous locomotor activity using actophotometer’ and hypnotic activity by ‘Prolongation of ketamine-induced sleeping time’. Six male mice were used for each of the groups and postdose, all the six that received diazepam had shown an inhibition of aggression, whereas in the test group, five of six mice and none in the control group had shown an inhibition of aggression (P = 0.0007). Similarly, for the sedative activity, the total number of spontaneous locomotor activity at 30 min following drug administration was found to be 364.67 ± 10.74, 123.16 ± 8.33, and 196.67 ± 3.7, while at 60 min it was found to be 209 ± 12.98, 49 ± 5.78, and 92 ± 2.5 (mean ± SD) for the control, standard, and test groups of mice respectively (P < 0.001). Hypnotic activity was measured by prolongation of ketamine-induced sleeping time wherein the onset and duration of loss of righting reflex were compared among each group of mice. The time in minutes for the onset in control, standard, and test groups was 4.01 ± 0.22, 1.23 ± 0.05, and 2.23 ± 0.07, respectively. The duration of loss of righting reflex was 44.23 ± 0.59, 56.03 ± 1.34, and 50.57 ± 0.36, respectively. Both these were statistically significant (P < 0.001). However, more clinical studies are needed to assess the long-term effects of the extract in humans. PMID:24948855

Effect of ketamine, pentobarbital, and morphine on Tc-99m-DISIDA hepatobiliary kinetics

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

Durakovic, A.; Dubois, A.

1985-05-01

The purpose of this study was to evaluate hapatobiliary kinetics of Tc-99m-DISIDA in dogs after administration of anesthetic sedative or narcotic agents. Four groups of six male Beagle dogs were studied as a non-treated control group and after parenteral administration of ketamine (30 mg/kg IM), pentobarbital (25 mg/kg IV) or morphine (1 mg/kg IV). Each animal was injected with 4 mCi Tc-99m-DISIDA and hepatobiliary scintigraphic studies were obtained using a gamma camera with parallel hole multipurpose collimator and an A/sup 3/ MDS computer. The authors determined; peak activity of Tc-99m-DISIDA in the liver, visualization and peak activity of gallbladder, andmore » intestinal visualization of Tc-99m-DISIDA. Total bilirubin, LDH, SGOT and SGPT were not modified significantly after any drug compared to control. The results showed that two commonly used anesthetics and sedatives (ketamine and pentobarbital) have dramatic and opposite effects on extrahepatic biliary kinetics. Furthermore, ketamine, but not pentobarbital, significantly accelerates intrahepatic biliary kinetics. Finally, as expected, morphine delayed extrahepatic biliary kinetics. Thus, studies of biliary kinetics should be interpreted with caution when measurements are made after administration of anesthetic, sedative or narcotic agents.« less

Synthesis, anticonvulsant, sedative and anxiolytic activities of novel annulated pyrrolo[1,4]benzodiazepines.

PubMed

Sorra, Kumaraswamy; Chen, Chien-Shu; Chang, Chi-Fen; Pusuluri, Srinivas; Mukkanti, Khagga; Wu, Chi-Rei; Chuang, Ta-Hsien

2014-09-18

Four new pentacyclic benzodiazepine derivatives (PBDTs 13-16) were synthesized by conventional thermal heating and microwave-assisted intramolecular cyclocondensation. Their anticonvulsant, sedative and anxiolytic activities were evaluated by drug-induced convulsion models, a pentobarbital-induced hypnotic model and an elevated plus maze in mice. PBDT 13, a triazolopyrrolo[2,1-c][1,4]benzodiazepin-8-one fused with a thiadiazolone ring, exhibited the best anticonvulsant, sedative and anxiolytic effects in our tests. There was no significant difference in potency between PBDT 13 and diazepam, and we proposed that the action mechanism of PBDT 13 could be similar to that of diazepam via benzodiazepine receptors.

Hypnotic induction is followed by state-like changes in the organization of EEG functional connectivity in the theta and beta frequency bands in high-hypnotically susceptible individuals

PubMed Central

Jamieson, Graham A.; Burgess, Adrian P.

2014-01-01

Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information) between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs) and 11 low susceptible (lows) participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH) and the imaginary component of coherence (iCOH), which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1–3.9 Hz), theta (4–7.9 Hz) alpha (8–12.9 Hz), beta1 (13–19.9 Hz), beta2 (20–29.9 Hz) and gamma (30–45 Hz). The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized “hypnotic-state.” PMID:25104928

Effects of three hypnotics on the sleep-wakefulness cycle in sleep-disturbed rats.

PubMed

Shinomiya, Kazuaki; Shigemoto, Yuki; Omichi, Junji; Utsu, Yoshiaki; Mio, Mitsunobu; Kamei, Chiaki

2004-04-01

New sleep disturbance model in rats is useful for estimating the characteristics of some hypnotics. The present study was undertaken to investigate the utility of a sleep disturbance model by placing rats on a grid suspended over water using three kinds of hypnotics, that is, short-acting benzodiazepine (triazolam), intermediate-acting benzodiazepine (flunitrazepam) and long-acting barbiturate (phenobarbital). Electrodes for measurement of EEG and EMG were implanted into the frontal cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalogram. SleepSign ver.2.0 was used for EEG and EMG analysis. Total times of wakefulness, non-REM and REM sleep were measured from 0900 to 1500 hours. In rats placed on the grid suspended over water up to 1 cm under the grid surface, not only triazolam but also flunitrazepam and phenobarbital caused a shortening of sleep latency. Both flunitrazepam and phenobarbital were effective in increasing of total non-REM sleep time in rats placed on sawdust or the grid, and the effects of both drugs in rats placed on the grid were larger than those in rats placed on sawdust. Measurement of the hourly non-REM sleep time was useful for investigating the peak time and duration of effect of the three hypnotics. Phenobarbital showed a decrease in total REM sleep time in rats placed on the grid, although both triazolam and flunitrazepam were without effect. The present insomnia model can be used as a sleep disturbance model for testing not only the sleep-inducing effects but also the sleep-maintaining effects including non-REM sleep and REM sleep of hypnotics.

Effects of hypnotic drugs on performance before and after sleep

NASA Technical Reports Server (NTRS)

Kales, A.; Bixler, E. O.; Kales, J. D.

1975-01-01

The effects of various hypnotics on sleep stage parameters and on the parameters of effectiveness were evaluated along with the effects of several commonly used yet distinctly different hypnotics on daytime performance. The effects on daytime performance of two nonhypnotics commonly used in the space program were also examined.

The neurophysiology of pain perception and hypnotic analgesia: implications for clinical practice.

PubMed

Jensen, Mark P

2008-10-01

Although there remains much to be learned, a great deal is now known about the neurophysiological processes involved in the experience of pain. Research confirms that there is no single focal "center" in the brain responsible for the experience of pain. Rather, pain is the end product of a number of integrated networks that involve activity at multiple cortical and subcortical sites. Our current knowledge about the neurophysiological mechanisms of pain has important implications for understanding the mechanisms underlying the effects of hypnotic analgesia treatments, as well as for improving clinical practice. This article is written for the clinician who uses hypnotic interventions for pain management. It begins with an overview of what is known about the neurophysiological basis of pain and hypnotic analgesia, and then discusses how clinicians can use this knowledge for (1) organizing the types of suggestions that can be used when providing hypnotic treatment, and (2) maximizing the efficacy of hypnotic interventions in clients presenting with pain problems.

A causal model explaining the relationships governing beliefs, attitudes, and hypnotic responsiveness.

PubMed

Shimizu, Takahiro

2014-01-01

The author developed a new scale aimed at measuring beliefs about "hypnotic states" and investigated the influence of such beliefs and attitudes on hypnotic responses in a large sample of Japanese undergraduate students. Exploratory factor analysis of this new questionnaire examining beliefs about hypnotic states yielded four factors: Dissociative or Depersonalized Experience, Loss of Self-Control, Therapeutic Expectation, and Arousing Extraordinary Ability. The results of structural equation modeling showed that Therapeutic Expectation and Arousing Extraordinary Ability influenced hypnotizability through attitudes toward hypnosis, while also directly affecting subjective experiences without mediating attitudes. Present findings suggest that it is more effective to enhance therapeutic expectations than to correct misconceptions about hypnotic states in modification of patients' beliefs before initiating treatment.

Feasibility of Music and Hypnotic Suggestion to Manage Chronic Pain.

PubMed

Johnson, Alisa J; Kekecs, Zoltan; Roberts, R Lynae; Gavin, Russell; Brown, Kathleen; Elkins, Gary R

2017-01-01

The authors investigated the feasibility and possible effects of hypnotic suggestion and music for chronic pain. Ten people completed the 2-week intervention that consisted of daily listening to hypnotic suggestions combined with music. Averaged subjective pain intensity, pain bothersomeness, overall distress, anxiety, and depression decreased from baseline to endpoint. Participants rated pre- and postlistening pain intensity and pain bothersomeness decreased for each session. Information provided during end-of-study interviews indicated all participants were satisfied with treatment and felt they benefited from being in the study. Means and standard deviations are reported for outcome measures and a case study is provided. This preliminary study supports the use of a combined hypnotic suggestion and music intervention for chronic pain.

A dangerous method? The German discourse on hypnotic suggestion therapy around 1900

PubMed Central

Maehle, Andreas-Holger

2017-01-01

In the late nineteenth century, German-speaking physicians and psychiatrists intensely debated the benefits and risks of treatment by hypnotic suggestion. While practitioners of the method sought to provide convincing evidence for its therapeutic efficacy in many medical conditions, especially nervous disorders, critics pointed to dangerous side effects, including the triggering of hysterical attacks or deterioration of nervous symptoms. Other critics claimed that patients merely simulated hypnotic phenomena in order to appease their therapist. A widespread concern was the potential for abuses of hypnosis, either by giving criminal suggestions or in the form of sexual assaults on hypnotized patients. Official inquiries by the Prussian Minister for Religious, Educational and Medical Affairs in 1902 and 1906 indicated that relatively few doctors practised hypnotherapy, whereas the method was increasingly used by lay healers. Although the Ministry found no evidence for serious harm caused by hypnotic treatments, whether performed by doctors or by lay healers, many German doctors seem to have regarded hypnotic suggestion therapy as a problematic method and abstained from using it.

An update on age, hypnotic suggestibility, and gender: a brief report.

PubMed

Page, Roger A; Green, Joseph P

2007-04-01

This study assessed the relationship of age and hypnotic suggestibility in an effort to partially update the findings of Morgan and Hilgard (1973). A total of 2,660 undergraduates were administered the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A; Shor & Orne, 1962) over a 7 year period. Consistent with Morgan and Hilgard's results, we found a general trend for hypnotic suggestibility scores to decrease from age 17 to 40, and then increase thereafter. We also found that female participants scored higher on the HGSHS: A compared with males across the various age ranges that we sampled.

The Risk of Pneumonia in Older Adults Using Nonbenzodiazepine Hypnotics.

PubMed

Jung, Stephen; Spence, Michele M; Escasa, Nina M; Lee, Eric A; Hui, Rita L; Gibbs, Nancy E

2016-08-01

Previous studies have shown an increased risk of pneumonia with benzodiazepines (BZD) and an increased risk of any infection with non-BZD hypnotics, but no analysis has specifically investigated the risk of pneumonia with non-BZD hypnotic use. To evaluate the risk of pneumonia associated with non-BZD hypnotic use in the elderly. This was a retrospective case-control study of members aged 65 years and older enrolled in an integrated health care system. Cases were identified as patients aged 65 years and older with a diagnosis of pneumonia from January 2011 to December 2012. Controls were matched in a 4:1 ratio to cases based on age, gender, and active enrollment. Non-BZD hypnotic exposure was evaluated for all cases and controls 1 year before the index date. Proximity of exposure to index date and duration of use were analyzed. Conditional logistic regression adjusted for covariates was performed. We identified 51,029 cases with pneumonia and matched 188,391 controls without pneumonia. Of the cases with pneumonia, 5.5% (2,790) of cases had exposure to a non-BZD hypnotic, compared with 3.4% (6,345) of controls. Non-BZD hypnotic exposure was associated with an increased risk of pneumonia (OR = 1.14; 95% CI = 1.08-1.20). When exposure was stratified by proximity to index date, only current exposure was associated with an increased risk of pneumonia (OR = 1.27; 95% CI = 1.18-1.36). Short-term exposure was associated with a relatively higher risk of pneumonia (OR = 1.57; 95% CI = 1.39-1.77) compared with long-term use (OR = 1.16; 95% CI = 1.06-1.25). Current use of non-BZD hypnotics in older adults is associated with an increased risk of pneumonia. The findings of this study provide additional support for reducing the use of non-BZD hypnotics in older adults and for pursuing safer alternatives for treating insomnia. No outside funding supported this study. At the time of this study, Jung was a PGY2 resident in drug information at Kaiser Permanente Drug Information

Recurrence quantification analysis of electroencephalograph signals during standard tasks of Waterloo-Stanford group scale of hypnotic susceptibility.

PubMed

Yargholi, Elahe'; Nasrabadi, Ali Motie

2015-01-01

The purpose of this study was to apply RQA (recurrence quantification analysis) on hypnotic electroencephalograph (EEG) signals recorded after hypnotic induction while subjects were doing standard tasks of the Waterloo-Stanford Group Scale (WSGS) of hypnotic susceptibility. Then recurrence quantifiers were used to analyse the influence of hypnotic depth on EEGs. By the application of this method, the capability of tasks to distinguish subjects of different hypnotizability levels was determined. Besides, medium hypnotizable subjects showed the highest disposition to be inducted by hypnotizer. Similarities between brain governing dynamics during tasks of the same type were also observed. The present study demonstrated two remarkable innovations; investigating the EEGs of the hypnotized as doing mental tasks of Waterloo-Stanford Group Scale (WSGS) and applying RQA on hypnotic EEGs.

[Determining factors for the use of anxiolytic and hypnotic drugs in the elderly].

PubMed

Téllez-Lapeira, Juan M; López-Torres Hidalgo, Jesús; Gálvez-Alcaraz, Luis; Párraga-Martínez, Ignacio; Boix-Gras, Clotilde; García-Ruiz, Antonio

To estimate the prevalence of self-reported anxiety/hypnotics use in adults 65 years and older and identify potential factors that determine the use of these drugs. Cross-sectional study conducted on a study population of 1,161 non-institutionalised adults 65 years old and older with enough ability to conduct a personal interview. Participants were randomly selected from health care registers. The main outcomes of interest included consumption of anxiolytics, hypnotics and other drugs (filed by ATC classification system), mood (based on the Yesavage geriatric depression scale), cognitive status (Pfeiffer questionnaire), physical-functional assessment of basic activities of daily living (Katz index), health problems (ICPC-2 classification WONCA), and sociodemographic variables. The prevalence of self-reported anxiety/hypnotics consumption was 16.6% (95% CI: 14.5 - 18.7), of which 90.5% were benzodiazepines (BZD), mainly lorazepam (39.4% of BZD). Long half-life BZD accounted for 24.7% of BZD. Hypnotics accounted for 27.5% of anxiolytics/hypnotics. The use of sedatives/hypnotics was independently associated with other drugs (non-psychotropics) consumption (OR 6.8, 95% CI: 2.1-22.0), presence of established depression (OR: 2.5; 95% CI: 1.0 -5.9), presence of 4 or more comorbidities (OR: 2.0; 95% CI: 1.4-2.9), being female (OR 2.1, 95% CI: 1.5-3.1) and being dependent for basic activities of daily living (OR: 1.8, 95% CI: 1.1-2.9). The prevalence of sedatives/hypnotics use in the elderly from Albacete is high. Several factors were identified as potential determinants of sedatives/hypnotics use in our study population. It will be important to evaluate the misuse of these drugs in order to develop effective, efficient and safe prescription strategies. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit

PubMed Central

Kripke, Daniel F.

2016-01-01

This is a review of hypnotic drug risks and benefits, reassessing and updating advice presented to the Commissioner of the Food and Drug Administration (United States FDA). Almost every month, new information appears about the risks of hypnotics (sleeping pills). This review includes new information on the growing USA overdose epidemic, eight new epidemiologic studies of hypnotics’ mortality not available for previous compilations, and new emphasis on risks of short-term hypnotic prescription. The most important risks of hypnotics include excess mortality, especially overdose deaths, quiet deaths at night, infections, cancer, depression and suicide, automobile crashes, falls, and other accidents, and hypnotic-withdrawal insomnia. The short-term use of one-two prescriptions is associated with greater risk per dose than long-term use. Hypnotics are usually prescribed without approved indication, most often with specific contraindications, but even when indicated, there is little or no benefit. The recommended doses objectively increase sleep little if at all, daytime performance is often made worse, not better, and the lack of general health benefits is commonly misrepresented in advertising. Treatments such as the cognitive behavioral treatment of insomnia and bright light treatment of circadian rhythm disorders might offer safer and more effective alternative approaches to insomnia. PMID:27303633

The "hypnotic state" and eye movements: Less there than meets the eye?

PubMed Central

Nordhjem, Barbara; Marcusson-Clavertz, David; Holmqvist, Kenneth

2017-01-01

Responsiveness to hypnotic procedures has been related to unusual eye behaviors for centuries. Kallio and collaborators claimed recently that they had found a reliable index for "the hypnotic state" through eye-tracking methods. Whether or not hypnotic responding involves a special state of consciousness has been part of a contentious debate in the field, so the potential validity of their claim would constitute a landmark. However, their conclusion was based on 1 highly hypnotizable individual compared with 14 controls who were not measured on hypnotizability. We sought to replicate their results with a sample screened for High (n = 16) or Low (n = 13) hypnotizability. We used a factorial 2 (high vs. low hypnotizability) x 2 (hypnosis vs. resting conditions) counterbalanced order design with these eye-tracking tasks: Fixation, Saccade, Optokinetic nystagmus (OKN), Smooth pursuit, and Antisaccade (the first three tasks has been used in Kallio et al.'s experiment). Highs reported being more deeply in hypnosis than Lows but only in the hypnotic condition, as expected. There were no significant main or interaction effects for the Fixation, OKN, or Smooth pursuit tasks. For the Saccade task both Highs and Lows had smaller saccades during hypnosis, and in the Antisaccade task both groups had slower Antisaccades during hypnosis. Although a couple of results suggest that a hypnotic condition may produce reduced eye motility, the lack of significant interactions (e.g., showing only Highs expressing a particular eye behavior during hypnosis) does not support the claim that eye behaviors (at least as measured with the techniques used) are an indicator of a "hypnotic state.” Our results do not preclude the possibility that in a more spontaneous or different setting the experience of being hypnotized might relate to specific eye behaviors. PMID:28846696

The relationship between the hypnotic induction profile and the stanford hypnotic susceptibility scale, form C: revisited.

PubMed

Frischholz, Edward J; Tryon, Warren W; Spiegel, Herbert; Fisher, Stanley

2015-01-01

Hilgard's comment raises some important issues, although many of these have little to do with the primary purpose of the study under discussion. This purpose was to objectively examine the relationship between three conceptually and operationally different procedures for measuring hypnotic responsivity. Hilgard's concern over the magnitude of the correlation between the HIP and SHSS:C is unfounded. A cross-validated correlation of .66 was found between the HIP and SHSS:C in a new sample of 44 student volunteers. This demonstrates that the HIP correlates about the same with SHSS:C as the Harvard Group Scale of Hypnotic Susceptibility. Hilgard's conception of the Eye-Roll (ER) hypothesis is clarified. Evidence which utilizes all cases in the correlational analysis is presented in support of the ER hypothesis. Happily, we all agree on a new methodology which will be definitive in testing the validity of the ER hypothesis.

Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.

PubMed

Tasker, Robert C; Goodkin, Howard P; Sánchez Fernández, Iván; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2016-10-01

To describe pediatric patients with convulsive refractory status epilepticus in whom there is intention to use an IV anesthetic for seizure control. Two-year prospective observational study evaluating patients (age range, 1 mo to 21 yr) with refractory status epilepticus not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Nine pediatric hospitals in the United States. In a cohort of 111 patients with refractory status epilepticus (median age, 3.7 yr; 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. The median (interquartile range) ICU length of stay was 10 (3-20) days. Up to four "cycles" of serial anesthetic therapy were used, and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9-34) hours for the first cycle and longer when a second cycle was required (30 [4-120] hr; p = 0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam nonresponders, transition to a second agent occurred after a median of 1 day. Most patients (94%) experienced seizure termination with these two therapies. Midazolam and pentobarbital remain the mainstay of continuous infusion therapy for refractory status epilepticus in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure, may be possible in a multicenter

Not all group hypnotic suggestibility scales are created equal: individual differences in behavioral and subjective responses.

PubMed

Barnes, Sean M; Lynn, Steven Jay; Pekala, Ronald J

2009-03-01

To examine the influence of hypnotic suggestibility testing as a source of individual differences in hypnotic responsiveness, we compared behavioral and subjective responses on three scales of hypnotic suggestibility: The Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS: A; Shor, R. E., Orne, E. C. (1962). Harvard Group Scale of Hypnotic Susceptibility. Berlin: Consulting Psychologists Press); the Carleton University Responsiveness to Suggestion Scale (CURSS; Spanos, N. P., Radtke, H. L., Hodgins, D. C., Stam, H. J., Bertrand, L. D. (1983b). The Carleton University Responsiveness to Suggestion Scale: Normative data and psychometric properties. Psychological Reports, 53, 523-535); and the Group Scale of Hypnotic Ability (GSHA; Hawkins, R., Wenzel, L. (1999). The Group Scale of Hypnotic Ability and response booklet. Australian Journal of Clinical and Experimental Hypnosis, 27, 20-31). Behavioral and subjective responses to the CURSS were significantly different than those on the HGSHS: A and GSHA. More participants were classified as "low suggestible" on the CURSS and they reported subjective experiences more similar to everyday mentation. Attitudes and expectancies of participants who received the GSHA were less predictive of responding, but rates of responding and subjective experiences were similar on the GSHA and the HGSHS: A. Discussion focuses on implications for the use of group hypnotic suggestibility scales.

Dissociated control as a signature of typological variability in high hypnotic suggestibility.

PubMed

Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

2011-09-01

This study tested the prediction that dissociative tendencies modulate the impact of a hypnotic induction on cognitive control in different subtypes of highly suggestible individuals. Low suggestible (LS), low dissociative highly suggestible (LDHS), and high dissociative highly suggestible (HDHS) participants completed the Stroop color-naming task in control and hypnosis conditions. The magnitude of conflict adaptation (faster response times on incongruent trials preceded by an incongruent trial than those preceded by a congruent trial) was used as a measure of cognitive control. LS and LDHS participants displayed marginally superior up-regulation of cognitive control following a hypnotic induction, whereas HDHS participants' performance declined. These findings indicate that dissociative tendencies modulate the influence of a hypnotic induction on cognitive control in high hypnotic suggestibility and suggest that HS individuals are comprised of distinct subtypes with dissimilar cognitive profiles. Copyright © 2010 Elsevier Inc. All rights reserved.

Cerebral and brainstem electrophysiologic activity during euthanasia with pentobarbital sodium in horses.

PubMed

Aleman, M; Williams, D C; Guedes, A; Madigan, J E

2015-01-01

An overdose of pentobarbital sodium administered i.v. is the most commonly used method of euthanasia in veterinary medicine. Determining death after the infusion relies on the observation of physical variables. However, it is unknown when cortical electrical activity and brainstem function are lost in a sequence of events before death. To examine changes in the electrical activity of the cerebral cortex and brainstem during an overdose of pentobarbital sodium solution for euthanasia. Our testing hypothesis is that isoelectric pattern of the brain in support of brain death occurs before absence of electrocardiogram (ECG) activity. Fifteen horses requiring euthanasia. Prospective observational study. Horses with neurologic, orthopedic, and cardiac illnesses were selected and instrumented for recording of electroencephalogram, electrooculogram, brainstem auditory evoked response (BAER), and ECG. Physical and neurologic (brainstem reflexes) variables were monitored. Loss of cortical electrical activity occurred during or within 52 seconds after the infusion of euthanasia solution. Cessation of brainstem function as evidenced by a lack of brainstem reflexes and disappearance of the BAER happened subsequently. Despite undetectable heart sounds, palpable arterial pulse, and mean arterial pressure, recordable ECG was the last variable to be lost after the infusion (5.5-16 minutes after end of the infusion). Overdose of pentobarbital sodium solution administered i.v. is an effective, fast, and humane method of euthanasia. Brain death occurs within 73-261 seconds of the infusion. Although absence of ECG activity takes longer to occur, brain death has already occurred. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial

PubMed Central

Pérez-Bárcena, Jon; Llompart-Pou, Juan A; Homar, Javier; Abadal, Josep M; Raurich, Joan M; Frontera, Guillem; Brell, Marta; Ibáñez, Javier; Ibáñez, Jordi

2008-01-01

Introduction Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. Methods This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation ≤ 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. Results A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis – undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital – thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. Conclusions Thiopental appeared to be more effective than

Outcomes in Children Treated with Pentobarbital Infusion for Refractory and Super-Refractory Status Epilepticus.

PubMed

Erklauer, Jennifer; Graf, Jeanine; McPherson, Mona; Anderson, Anne; Wilfong, Angus; Minard, Charles G; Loftis, Laura

2018-03-26

Functional neurologic outcome for children with refractory and super-refractory status epilepticus has not been well defined. Retrospective chart review including children age 0-17 years who received pentobarbital infusion from 2003 to 2016 for status epilepticus. Outcomes were defined in terms of mortality, need for new medical technology assistance at hospital discharge and functional neurologic outcome determined by pediatric cerebral performance category score (PCPC). Potential patient characteristics associated with functional neurologic outcome including age, sex, ethnicity, etiology of the status epilepticus, and duration of pentobarbital infusion were evaluated. Forty children met inclusion criteria. In-hospital mortality was 30% (12/40). Of survivors, 21% (6/28) returned to baseline PCPC while half (14/28) declined in function ≥ 2 PCPC categories at hospital discharge. 25% (7/28) of survivors required tracheostomy and 27% (7/26) required new gastrostomy. Seizures persisted at discharge for most patients with new onset status epilepticus while the majority of patients with known epilepsy returned to baseline seizure frequency. Etiology (p = 0.015), PCPC at admission (p = 0.0006), new tracheostomy (p = 0.012), and new gastrostomy tube (p = 0.012) were associated with increase in PCPC score ≥ 2 categories in univariable analysis. Duration of pentobarbital infusion (p = 0.005) and length of hospital stay (p = 0.056) were longer in patients who demonstrated significant decline in neurologic function. None of these variables maintained statistical significance when multiple logistic regression model adjusting for PCPC score at admission was applied. At long-term follow-up, 36% (8/22) of children demonstrated improvement in PCPC compared to discharge and 23% (5/22) showed deterioration including three additional deaths. Mortality in this population was high. The majority of children experienced some degree of disability at discharge. Despite

Neuro-Hypnotism: Prospects for Hypnosis and Neuroscience

PubMed Central

Kihlstrom, John F.

2012-01-01

The neurophysiological substrates of hypnosis have been subject to speculation since the phenomenon got its name. Until recently, much of this research has been geared toward understanding hypnosis itself, including the biological bases of individual differences in hypnotizability, state-dependent changes in cortical activity occurring with the induction of hypnosis, and the neural correlates of response to particular hypnotic suggestions (especially the clinically useful hypnotic analgesia). More recently, hypnosis has begun to be employed as a method for manipulating subjects' mental states, both cognitive and affective, to provide information about the neural substrates of experience, thought, and action. This instrumental use of hypnosis is particularly well-suited for identifying the neural correlates of conscious and unconscious perception and memory, and of voluntary and involuntary action. PMID:22748566

Sleep-Promoting Effects and Possible Mechanisms of Action Associated with a Standardized Rice Bran Supplement.

PubMed

Yang, Hyejin; Yoon, Minseok; Um, Min Young; Lee, Jaekwang; Jung, Jonghoon; Lee, Changho; Kim, Yun-Tai; Kwon, Sangoh; Kim, Boknam; Cho, Suengmok

2017-05-18

Natural sleep aids are becoming more popular due to the widespread occurrence of sleep disorders. The objective of this study was to assess the sleep-promoting effects of rice bran-a product that is considered as a functional ingredient. To evaluate the sleep-promoting effects of a standardized rice bran supplement (RBS), we employed a pentobarbital-induced sleep test and conducted analyses of sleep architecture. In addition, the effect of RBS on a caffeine-induced sleep disturbance was investigated. Oral administration of RBS (500 and 1000 mg/kg) produced a significant decrease in sleep latency and increase in sleep duration in pentobarbital-induced sleep in mice. Moreover, both RBS (1000 mg/kg) and doxepin hydrochloride (histamine H₁ receptor antagonist, 30 mg/kg) counteracted a caffeine-induced sleep disturbance in mice. In terms of sleep phases, RBS (500 mg/kg) promoted non-rapid eye movement sleep for the first 3 h following its administration. Lastly, we unveiled a possible mechanism for RBS action as the hypnotic effect of RBS was blocked by a histamine H₁ receptor agonist. The present study revealed sleep-promoting effects of RBS using various animal assays. Such effects seem to be mediated through the histaminergic system. Our findings suggest that RBS may be a promising natural aid for relieving sleep problems.

Thirteen days: Joseph Delboeuf versus Pierre Janet on the nature of hypnotic suggestion.

PubMed

LeBlanc, André

2004-01-01

The problem of post-hypnotic suggestion was introduced in 1884. Give a hypnotic subject the post-hypnotic command to return in 13 days. Awake, the subject remembers nothing yet nonetheless fulfills the command to return. How then does the subject count 13 days without knowing it? In 1886, Pierre Janet proposed the concept of dissociation as a solution, arguing that a second consciousness kept track of time outside of the subject's main consciousness. Joseph Delboeuf, in 1885, and Hippolyte Bernheim, in 1886, proposed an alternative solution, arguing that subjects occasionally drifted into a hypnotic state in which they were reminded of the suggestion. This article traces the development of these competing solutions and describes some of Delboeuf's final reflections on the problem of simulation and the nature of hypnosis. Copyright 2004 Wiley Periodicals, Inc.

The Computer-Assisted Hypnosis Scale: Standardization and Norming of a Computer-Administered Measure of Hypnotic Ability.

ERIC Educational Resources Information Center

Grant, Carolyn D.; Nash, Michael R.

1995-01-01

In a counterbalanced, within subjects, repeated measures design, 130 undergraduates were administered the Computer-Assisted Hypnosis Scale (CAHS) and the Stanford Hypnotic Susceptibility Scale and were hypnotized. The CAHS was shown to be a psychometrically sound instrument for measuring hypnotic ability. (SLD)

Discrete response patterns in the upper range of hypnotic suggestibility: A latent profile analysis.

PubMed

Terhune, Devin Blair

2015-05-01

High hypnotic suggestibility is a heterogeneous condition and there is accumulating evidence that highly suggestible individuals may be comprised of discrete subtypes with dissimilar cognitive and phenomenological profiles. This study applied latent profile analysis to response patterns on a diverse battery of difficult hypnotic suggestions in a sample of individuals in the upper range of hypnotic suggestibility. Comparisons among models indicated that a four-class model was optimal. One class was comprised of very highly suggestible (virtuoso) participants, two classes included highly suggestible participants who were alternately more responsive to inhibitory cognitive suggestions or posthypnotic amnesia suggestions, and the fourth class consisted primarily of medium suggestible participants. These results indicate that there are discrete response profiles in high hypnotic suggestibility. They further provide a number of insights regarding the optimization of hypnotic suggestibility measurement and have implications for the instrumental use of hypnosis for the modeling of different psychological conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Gilles de la Tourette's criminal women: the many faces of fin de siècle hypnotism.

PubMed

Bogousslavsky, Julien; Walusinski, Olivier

2010-09-01

Gilles de la Tourette is now known for the disease which now bears his name, but his activities in the management of hysterics and in hypnotism, which gained him most of his lifetime reputation, have been largely forgotten. As one of the closest followers of Jean-Martin Charcot, he always remained faithful to his mentor's views, and was one of the most vehement defenders of La Salpêtrière school during the quarrel with Hippolyte Bernheim and the Nancy school on the question of the specificity of hypnotic susceptibility in hysteria. This controversy became critical during medico-legal assessment of crimes supposedly committed under hypnotic suggestion. Gilles de la Tourette's involvement in criminal hypnotism was striking, as shown by his own experiments, the most famous of which being his suggested poisoning of a colleague by Blanche Wittman, the celebrated Charcot's hysteric patient in the 1887 Brouillet's painting. Gilles de la Tourette also acted as expert in murder trials, and his Epilogue in the Gouffé's trunk case, where he affirmed that no murder in real life could be due to hypnotism, and considered that Gabrielle Bompard, the murderer's accomplice, was not under hypnotic suggestion, had a considerable impact. Finally, he was confronted to the issue of murder under hypnotism in his private life, since in 1893, a former patient, Rose Kamper, came and shot him in the head at his home, claiming that hypnotism sessions had changed her own person, and that she had been hypnotized "at distance". These acts from three very different "hysterical" women highlight the Salpêtrière's theories on hypnotism and their inner contradictions in the fin de siècle ambiance, a few years before Joseph Babinski renewed the concepts on hysteria.

Mediation and Moderation of Psychological Pain Treatments: Response Expectancies and Hypnotic Suggestibility

ERIC Educational Resources Information Center

Milling, Leonard S.; Reardon, John M.; Carosella, Gina M.

2006-01-01

The mediator role of response expectancies and the moderator role of hypnotic suggestibility were evaluated in the analogue treatment of pain. Approximately 1,000 participants were assessed for hypnotic suggestibility. Later, as part of a seemingly unrelated experiment, 188 of these individuals were randomly assigned to distraction,…

Residual effects of hypnotics: an update.

PubMed

Hindmarch, I

1991-07-01

The sedative/hypnotic benzodiazepines introduced worldwide in the early 1960s were acclaimed for their low chemical toxicity and safety in clinical use. A decade later, some researchers and clinicians found that while all the drugs had undoubted potency and efficacy as sleep inducers and maintainers, the trade-off in residual effects (e.g., excessive daytime tiredness, poor concentration, impaired psychomotor performance, lowered mental abilities) was cause for concern. These sequelae not only affected patients' safety and ability to perform daytime tasks, but were also counter-therapeutic; the daytime sleep that was produced interfered with the natural nocturnal sleep. In a recent study, the degree to which patient abilities were impaired was measured by a number of psychomotor tests. Benzodiazepines with a duration of clinical effect of less than 8 to 10 hours produced fewer, less frequent residual effects than those with a measurable activity in excess of the normal nocturnal sleep period.

Refractory Status Epilepticus in Children: intention-to-treat with continuous infusions of midazolam and pentobarbital

PubMed Central

Tasker, Robert C; Goodkin, Howard P; Fernández, Iván Sánchez; Chapman, Kevin E; Abend, Nicholas S; Arya, Ravindra; Brenton, James N; Carpenter, Jessica L; Gaillard, William D; Glauser, Tracy A; Goldstein, Joshua; Helseth, Ashley R; Jackson, Michele C; Kapur, Kush; Mikati, Mohamad A; Peariso, Katrina; Wainwright, Mark S; Wilfong, Angus A; Williams, Korwyn; Loddenkemper, Tobias

2016-01-01

Objective To describe pediatric patients with convulsive refractory status epilepticus (RSE) in whom there is intention-to-use an intravenous anesthetic for seizure control. Design Two-year prospective observational study evaluating patients (age range one month to 21 years) with RSE not responding to two antiepileptic drug classes and treated with continuous infusion of anesthetic agent. Setting Nine pediatric hospitals in the United States. Patients In a cohort of 111 patients with RSE (median age 3.7 years, 50% male), 54 (49%) underwent continuous infusion of anesthetic treatment. Main Results The median (interquartile range, IQR) intensive care unit length-of-stay was 10 (3–20) days. Up to four ‘cycles’ of serial anesthetic therapy were used and seizure termination was achieved in 94% by the second cycle. Seizure duration in controlled patients was 5.9 (1.9–34) hours for the first cycle, and longer when a second cycle was required (30 [4,−120] hours, p=0.048). Midazolam was the most frequent first-line anesthetic agent (78%); pentobarbital was the most frequently used second-line agent after midazolam failure (82%). An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint. In midazolam non-responders, transition to a second agent occurred after a median of one day. Most patients (94%) experienced seizure termination with these two therapies. Conclusions Midazolam and pentobarbital remains the mainstay of continuous infusion therapy for RSE in the pediatric patient. The majority of patients experience seizure termination within a median of 30 hours. These data have implications for the design and feasibility of future intervention trials. That is, testing a new anesthetic anticonvulsant after failure of both midazolam and pentobarbital is unlikely to be feasible in a pediatric study, whereas a decision to test an alternative to pentobarbital, after midazolam failure

The effect of high mesencephalic transection (cerveau isolé) and pentobarbital on basal forebrain mechanisms of EEG synchronization.

PubMed

Obál, F; Benedek, G; Szikszay, M; Obál, F

1979-01-01

A study was made of the effects of high mesencephalic transection (cerveau isolé) and low doses of pentobarbital on the cortical synchronizations elicited in acute immobilized cats by (a) low frequency stimulation of the lateral hypothalamus (HL) and nucleus ventralis anterior thalami (VA) and (b) by low and high frequency stimulation of the laterobasal preoptic region (RPO) and olfactory tubercle (TbOf). The results obtained were as follows: (1) The synchronizations induced by basal forebrain stimulations were found to survive in acute cerveau isolé cats, moreover, even a facilitation of the synchronizing effect were observed. (2) A gradual facilitation was observed upon TbOf and RPO stimulation, while in the case of VA and HL stimulations, the facilitation appeared immediately after the transection. (3) Low doses of pentobarbital depressed the cortical effects of TbOf stimulation, while an increase of the synchronizing effect of low frequency VA and HL stimulation was found. The observations suggested that (i) the synchronizing mechanism in the ventral part of the basal forebrain (RPO and TbOf) differs from that of the thalamus and HL; (ii) the basal forebrain synchronizing mechanism is effective without the contribution of the brain stem; (iii) the mechanism responsible for the synchronizing effect of low frequency HL stimulation is similar as that described for the thalamus.

Guaifenesin alone or in combination with ketamine or sodium pentobarbital as an anesthetic in rabbits.

PubMed Central

Olson, M E; McCabe, K; Walker, R L

1987-01-01

Guaifenesin was administered alone and in combination with ketamine or sodium pentobarbital to adult New Zealand white rabbits. A solution of 5% guaifenesin in 5% dextrose given intravenously at a dosage of 200 mg/kg, abolished the pedal, palpebral and corneal reflexes for up to 15 minutes with little influence on cardiopulmonary function. Guaifenesin (200 mg/kg, intravenously) and ketamine (50 mg/kg, intramuscularly) produced effective and safe surgical anesthesia for over 30 minutes. This combination mildly depressed respiratory rate but heart rate and arterial blood pressure were not significantly affected. Guaifenesin (200 mg/kg, intravenously) was combined with sodium pentobarbital (20 mg/kg, intravenously) to produce surgical anesthesia for a period of more than 30 minutes. This combination depressed respiratory rate, produced a tachycardia and decreased arterial blood pressure. PMID:3651894

High prevalence of insomnia and hypnotic use in patients visiting their general practitioner.

PubMed

Bjorvatn, Bjørn; Meland, Eivind; Flo, Elisabeth; Mildestvedt, Thomas

2017-02-01

Sleep problems are common in the general population, but there are few prevalence studies among patients visiting their GP. Since sleep problems frequently co-occur with existing psychological and somatic conditions, the prevalence is likely to be higher in patients visiting their GPs compared to the prevalence in the general population. To estimate the prevalence of insomnia [based on the Diagnostic and Statistical Manual for Mental disorders (DSM)-version IV] and hypnotic use among patients in general practice and to evaluate whether the prevalence depended on sex and age. Questionnaire data were collected by 66 medical students while deployed in different general practices during their last year of school. A total of 1346 (response rate 74%) consecutive and unselected patients visiting their GPs answered the validated Bergen Insomnia Scale (BIS) and single questions on self-reported sleep problems and hypnotic use. The prevalence of insomnia according to BIS was 53.6%. Sleep problems (based on the single question) were self-reported by 55.8%, with 18.0% reporting to experience sleep problems a lot/very much. Hypnotic use was reported by 16.2% (daily use by 5.5%). Insomnia and hypnotic use were all more prevalent in females compared with males. Hypnotic use increased with age, whereas the prevalence of insomnia was highest in the younger age groups. Insomnia and hypnotic use were very prevalent among patients visiting their GPs. As insomnia can be effectively treated, we maintain that the diagnosis has a high pay-off and should earn greater awareness in GP's diagnostic evaluation and management. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hypnotism as a Function of Trance State Effects, Expectancy, and Suggestibility: An Italian Replication.

PubMed

Pekala, Ronald J; Baglio, Francesca; Cabinio, Monia; Lipari, Susanna; Baglio, Gisella; Mendozzi, Laura; Cecconi, Pietro; Pugnetti, Luigi; Sciaky, Riccardo

2017-01-01

Previous research using stepwise regression analyses found self-reported hypnotic depth (srHD) to be a function of suggestibility, trance state effects, and expectancy. This study sought to replicate and expand that research using a general state measure of hypnotic responsivity, the Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure (PCI-HAP). Ninety-five participants completed an Italian translation of the PCI-HAP, with srHD scores predicted from the PCI-HAP assessment items. The regression analysis replicated the previous research results. Additionally, stepwise regression analyses were able to predict the srHD score equally well using only the PCI dimension scores. These results not only replicated prior research but suggest how this methodology to assess hypnotic responsivity, when combined with more traditional neurophysiological and cognitive-behavioral methodologies, may allow for a more comprehensive understanding of that enigma called hypnosis.

Dissociative tendencies and individual differences in high hypnotic suggestibility.

PubMed

Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

2011-03-01

Inconsistencies in the relationship between dissociation and hypnosis may result from heterogeneity among highly suggestible individuals, in particular the existence of distinct highly suggestible subtypes that are of relevance to models of psychopathology and the consequences of trauma. This study contrasted highly suggestible subtypes high or low in dissociation on measures of hypnotic responding, cognitive functioning, and psychopathology. Twenty-one low suggestible (LS), 19 low dissociative highly suggestible (LDHS), and 11 high dissociative highly suggestible (HDHS) participants were administered hypnotic suggestibility scales and completed measures of free recall, working memory capacity, imagery, fantasy-proneness, psychopathology, and exposure to stressful life events. HDHS participants were more responsive to positive and negative hallucination suggestions and experienced greater involuntariness during hypnotic responding. They also exhibited impaired working memory capacity, elevated pathological fantasy and dissociative symptomatology, and a greater incidence of exposure to stressful life events. In contrast, LDHS participants displayed superior object visual imagery. These results provide further evidence for two highly suggestible subtypes: a dissociative subtype characterised by deficits in executive functioning and a predisposition to psychopathology, and a subtype that exhibits superior imagery and no observable deficits in functioning.

Hypnotic Relaxation Therapy and Sexual Function in PostmenopausalWomen: Results of a Randomized Clinical Trial.

PubMed

Johnson, Aimee K; Johnson, Alisa J; Barton, Debra; Elkins, Gary

2016-01-01

Sexual dysfunction is a common problem for postmenopausal women. This study, as part of a larger randomized controlled trial, examined the effect of hypnotic relaxation therapy on sexual dysfunction, a secondary study outcome, in postmenopausal women. Sexual function was assessed using the Sexual Activity Questionnaire (SAQ). Significant improvement in sexual pleasure and discomfort were reported following 5 weekly sessions of hypnotic relaxation therapy, compared with those receiving an attention control. Total SAQ scores showed significant improvement in the hypnotic relaxation therapy treatment group while holding baseline SAQ scores constant. Improvements showed a slight increase at the Week 12 follow-up. The results of this analysis provide initial support for the use of hypnotic relaxation therapy to improve sexual function in postmenopausal women.

A Simple Hypnotic Approach to Treat Test Anxiety in Medical Students and Residents.

ERIC Educational Resources Information Center

Hebert, Stephen W.

1984-01-01

A simple hypnotic procedure to treat test anxiety is described that was used successfully with medical students and residents at the Wake Forest University Medical Center. A light trace is obtained and then the student is told to take such a hypnotic "journey" the evening prior to the test. (MLW)

Stability of thiopental and pentobarbital in human plasma determined with a new easy and specific gas chromatography-mass spectrometry assay.

PubMed

Martens-Lobenhoffer, J

1999-08-01

A gas chromatographic-mass spectrometric (GC-MS) assay for the determination of thiopental and its main metabolite pentobarbital in human plasma is presented in this study. The sample preparation consists only in the addition of the internal standard barbital and an acidic extraction with ethyl acetate. Analytical separation is accomplished on a RTX-1 15 m x 0.25 mm capillary column with a film thickness of 0.5 micron. The effluent is observed by a mass selective detector operating in the single ion monitoring mode. The limits of detection are 5 ng/ml for pentobarbital and 10 ng/ml for thiopental, the intra-day variabilities are 2.2% and 4.0% and the inter-day variabilities are 3.3% and 7.1% at concentrations of 5 micrograms/ml, respectively. Applying this assay, the stability of thiopental and pentobarbital in human plasma was tested at concentrations of 5 micrograms/ml each. Thiopental is stable in human plasma at least over 41 days stored at -20 degrees C and 5 degrees C, respectively. A decay of about 2%/day is observed under storage at ambient temperature (19-20 degrees C). Pentobarbital is stable under all storage conditions. Methanolic solutions of thiopental are stable for 83 days under storage at 5 degrees C. Aqueous solutions of thiopental-sodium are stable for at least 23 days under storage at 5 degrees C or ambient temperature.

Sleep-Promoting Effects and Possible Mechanisms of Action Associated with a Standardized Rice Bran Supplement

PubMed Central

Yang, Hyejin; Yoon, Minseok; Um, Min Young; Lee, Jaekwang; Jung, Jonghoon; Lee, Changho; Kim, Yun-Tai; Kwon, Sangoh; Kim, Boknam; Cho, Suengmok

2017-01-01

Natural sleep aids are becoming more popular due to the widespread occurrence of sleep disorders. The objective of this study was to assess the sleep-promoting effects of rice bran—a product that is considered as a functional ingredient. To evaluate the sleep-promoting effects of a standardized rice bran supplement (RBS), we employed a pentobarbital-induced sleep test and conducted analyses of sleep architecture. In addition, the effect of RBS on a caffeine-induced sleep disturbance was investigated. Oral administration of RBS (500 and 1000 mg/kg) produced a significant decrease in sleep latency and increase in sleep duration in pentobarbital-induced sleep in mice. Moreover, both RBS (1000 mg/kg) and doxepin hydrochloride (histamine H1 receptor antagonist, 30 mg/kg) counteracted a caffeine-induced sleep disturbance in mice. In terms of sleep phases, RBS (500 mg/kg) promoted non-rapid eye movement sleep for the first 3 h following its administration. Lastly, we unveiled a possible mechanism for RBS action as the hypnotic effect of RBS was blocked by a histamine H1 receptor agonist. The present study revealed sleep-promoting effects of RBS using various animal assays. Such effects seem to be mediated through the histaminergic system. Our findings suggest that RBS may be a promising natural aid for relieving sleep problems. PMID:28524102

On-the-road driving performance and driving-related skills in older untreated insomnia patients and chronic users of hypnotics.

PubMed

Leufkens, T R M; Ramaekers, J G; de Weerd, A W; Riedel, W J; Vermeeren, A

2014-07-01

Many older adults report sleep problems and use of hypnotics. Several studies have shown that hypnotics can have acute adverse effects on driving the next morning. It is unclear however whether driving of chronic hypnotic users is impaired. Therapeutic effects on insomnia and development of tolerance may reduce the residual effects on driving. The present study aimed to compare actual driving performance and driving-related skills of chronic hypnotic users to good sleepers. To determine whether insomnia itself affects driving performance, driving and driving-related skills were compared between insomnia patients who do not or infrequently use hypnotics and good sleepers. Twenty-two frequent users of hypnotics (using hypnotics ≥ 4 nights per week for more than 3 months), 20 infrequent users (using hypnotics ≤ 3 nights per week), and 21 healthy, age-matched controls participated in this study. On the night before testing, all subjects were hospitalized for an 8-h sleep recorded by polysomnography. Frequent hypnotic users used their regular medication at bedtime (2330 hours), while infrequent users and controls received no medication. Cognitive performance (word learning, digit span, tracking, divided attention, vigilance, and inhibitory control) was assessed 8.5 h and driving performance between 10 and 11 h after bedtime and dosing. Polysomnographic recordings did not significantly differ between the groups, but the insomnia patients, treated or untreated, still reported subjective sleep complaints. Results show no differences in driving performance and driving-related skills between both groups of insomnia patients and controls. Driving performance in chronic users of hypnotics and untreated insomnia patients is not impaired. For chronic users, this may be due to prescription of relatively safe drugs and low doses. For untreated insomniacs, this corroborates previous findings showing an absence of neuropsychological deficits in this group of patients.

Assessment of Carbon Dioxide, Carbon Dioxide/Oxygen, Isoflurane and Pentobarbital Killing Methods in Adult Female Sprague-Dawley Rats.

PubMed

Chisholm, Jessica M; Pang, Daniel S J

2016-01-01

Exposure to carbon dioxide (CO2) gas as a killing method is aversive and exposure to high concentrations is likely to be painful. Bradycardia during exposure to CO2 is associated with nociception and pain. However, it is unclear if bradycardia occurs before loss of consciousness as definitions of loss of consciousness vary in the literature. The objectives of this study were to explore the relationship between recumbency, loss of righting reflex (LORR) and a quiescent electromyograph as measures of loss of consciousness, and identify the onset of bradycardia in relation to these measures. Our primary hypothesis was that CO2 exposure would result in bradycardia, which would precede LORR. Thirty-two adult, female Sprague-Dawley rats were instrumented with a telemetry device and randomly assigned to one of four killing methods (concentrations of 100% CO2, CO2 (70%)/O2 (30%), isoflurane (5%) and intraperitoneal pentobarbital (200 mg/kg). Time to achieve recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph, heart rate and apnea were recorded. The general order of progression was recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph and apnea. Recumbency preceded LORR in the majority of animals (CO2; 7/8, CO2/O2; 8/8, isoflurane; 5/8, pentobarbital; 4/8). Bradycardia occurred before recumbency in the CO2 (p = 0.0002) and CO2/O2 (p = 0.005) groups, with a 50% reduction in heart rate compared to baseline. The slowest (time to apnea) and least consistent killing methods were CO2/O2 (1180 ± 658.1s) and pentobarbital (875 [239 to 4680]s). Bradycardia, and consequently nociception and pain, occurs before loss of consciousness during CO2 exposure. Pentobarbital displayed an unexpected lack of consistency, questioning its classification as an acceptable euthanasia method in rats.

HYPNOTIC TACTILE ANESTHESIA: Psychophysical and Signal-Detection Analyses

PubMed Central

Tataryn, Douglas J.; Kihlstrom, John F.

2017-01-01

Two experiments that studied the effects of hypnotic suggestions on tactile sensitivity are reported. Experiment 1 found that suggestions for anesthesia, as measured by both traditional psychophysical methods and signal detection procedures, were linearly related to hypnotizability. Experiment 2 employed the same methodologies in an application of the real-simulator paradigm to examine the effects of suggestions for both anesthesia and hyperesthesia. Significant effects of hypnotic suggestion on both sensitivity and bias were found in the anesthesia condition but not for the hyperesthesia condition. A new bias parameter, C′, indicated that much of the bias found in the initial analyses was artifactual, a function of changes in sensitivity across conditions. There were no behavioral differences between reals and simulators in any of the conditions, though analyses of postexperimental interviews suggested the 2 groups had very different phenomenal experiences. PMID:28230465

Effects of Pentobarbital on Respiratory Functional Dynamics in Chronically Instrumented Guinea Pigs

DTIC Science & Technology

1991-01-01

inferior cerebellar peduncle; 10, inferior olive; LRN. lateral reticular nu- cleus; NSTTN. nucleus spinal tract of the trigeminal nerve ; STTN, spinal tract...reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP 06 15 sodium pentobarbital; respiration; chronic single unit 06 04 recording...diaphragmatic EMG; guinea pigs 19. ABSTRACT (Continue on reverse if necessary and identify by block number) CHANG. F.-C. T. Effects of pentobarhital

New benzodiazepine and Z-hypnotic users and disability pension: an eight-year nationwide observational follow-up study.

PubMed

Tvete, Ingunn F; Bjørner, Trine; Skomedal, Tor

2017-09-01

To compare how newly initiated treatment with benzodiazepines, Z-hypnotics or both associates with the reception of disability pension among 40,661 individuals of a working age. Prescription register study. Norwegian nationwide prescriptions socio-economic and disability status data. Cox regression analyses. New benzodiazepine or Z-hypnotic users. Time to receive disability pension given benzodiazepine or Z-hypnotic use or both. Additional analyses focused on the benzodiazepine first redeemed. Among new users 8.65% of Z-hypnotic users, 12.29% of benzodiazepines users and 13.96% of combined Z-hypnotic and benzodiazepine users became disability pensioners. Z-hypnotic users were weaker associated with becoming disability pensioners (HR = 0.78, CI: 0.73-0.84) and combined users were stronger associated (HR = 1.09, CI: 1.01-1.17), than benzodiazepine users. Women had higher risk than men for becoming disability pensioners. Higher age, lower education, previous drug use and psychiatrist as first prescriber were risk factors. Comparing first benzodiazepine redeemed; clonazepam initiators were stronger associated with becoming disability pensioners than diazepam initiators were (HR = 2.22, CI: 1.81-2.71). No differences between other benzodiazepine users were found. Adjusting for known risk factors gave lower risk for Z-hypnotic users compared to benzodiazepine users for receiving disability pension. Combined use increased the risk further. Clonazepam initiators are especially at risk. These findings may be helpful in prescribing situations to identify and guide individuals at risk for becoming disability pensioners.

Protracted ethanol withdrawal in rats: Tolerance to the anxiolytic effects of diazepam and pentobarbital but not phenobarbital

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

Lai, H.; Prather, P.L.

1990-02-26

Anxiety is a common symptom during ethanol withdrawal contributing to its continuous abuse and alcoholism. Ethanol withdrawal in rats produces an interoceptive discriminative stimulus (IDS) similar to that produced by the anxiogenic drug pentylenetetrazol (PTZ). This stimulus peaks at 12 hours after last dose of ethanol and thereafter the IDS is detected for several days (protracted withdrawal) by sensitization to a probe drug. previously, the authors have shown that during the protracted withdrawal, the IDS is enhanced by GABA receptor antagonists suggesting alteration of brain GABA systems. This report provides further evidence that chronic ethanol alters GABAergic systems. Rats weremore » trained to discriminate PTZ (20 mg/kg, ip) from saline. Diazepam, pentobarbital and phenobarbital blocked the PTZ-IDS dose dependently. Ethanol, 4.5% w/v, was then given in a nutritionally complete diet for a week. On termination of the ethanol diet, rats exhibited signs and symptoms of withdrawal which returned to baseline within 3 days. During the protracted withdrawal period, the authors then redetermined the blockade of the PTZ-IDS. Significant tolerance was observed to the effectiveness of diazepam and pentobarbital, but not to phenobarbital. Since diazepam and pentobarbital produce significantly more enhancement of GABAergic activity than does phenobarbital, these data further suggest alteration of brain GABAergic systems during protracted withdrawal from ethanol.« less

Comparison of tribromoethanol, ketamine/acetylpromazine, Telazol/xylazine, pentobarbital, and methoxyflurane anesthesia in HSD:ICR mice.

PubMed

Gardner, D J; Davis, J A; Weina, P J; Theune, B

1995-04-01

Variation in the duration of surgical anesthesia in mice prompted an evaluation of various commonly used anesthetics. Using biotelemetric technology, we evaluated the effects of six anesthetic regimens (tribromoethanol, ketamine and acetylpromazine in combination, Telazol and xylazine in two combinations, pentobarbital, and methoxyflurane) on temperature and activity. Six groups of four male HSD:ICR mice received one of the anesthetic regimens or an equivalent volume of saline. Induction time (time from anesthetic administration until righting reflex loss) and duration of anesthesia (loss of response to interdigital toe pinch) were evaluated. Methoxyflurane and both doses of Telazol combinations resulted in the shortest and most repeatable induction times. None of the mice in the ketamine/acetylpromazine- and pentobarbital-treated groups lost the interdigital toe pinch reflex. Duration of anesthesia was superior in the two Telazol/xylazine-treated groups. A direct correlation existed between duration of anesthesia and magnitude and duration of temperature reduction. Duration of anesthesia can be used to predict extent of hypothermia.

The Feasibility of Hypnotic Analgesia in Ameliorating Pain and Anxiety Among Adults Undergoing Needle Electromyography

PubMed Central

Slack, David; Nelson, Lonnie; Patterson, David; Burns, Stephen; Hakimi, Kevin; Robinson, Lawrence

2017-01-01

Objective Our hypothesis was that hypnotic analgesia reduces pain and anxiety during electromyography [EMG]. Design Prospective randomized controlled clinical trial at outpatient electrodiagnostic clinics in teaching hospitals. Just prior to EMG, 26 subjects were randomized to one of three 20 minute audio programs: (EDU) education about EMG (n=8); (HYP-C) hypnotic induction without analgesic suggestion (n=10) or; (HYP-ANLG) hypnotic induction with analgesic suggestion (n=8). The blinded electromyographer provided a post-hypnotic suggestion at the start of EMG. After EMG, subjects rated worst and average pain, and anxiety using visual analog scales. Results Mean values for the EDU, HYP-C and HYP-ANLG groups were not significantly different (mean ± sd): worst pain 67 ± 25, 42 ± 18, 49 ± 30: average pain 35 ± 26, 27 ± 14, 25 ± 22; anxiety 44 ± 41, 42 ± 23, 22 ± 24. When hypnosis groups were merged [n=18] and compared with the EDU condition [n=8], average and worst pain and anxiety were less for the hypnosis group than EDU, but this was statistically significant only for worst pain [hypnosis - 46 ± 24 vs. EDU - 67 ± 35, p=0.049] with a 31% average reduction. Conclusions A short hypnotic induction appears to reduce worst pain during EMG. PMID:18971768

Understanding hypnosis metacognitively: rTMS applied to left DLPFC increases hypnotic suggestibility.

PubMed

Dienes, Zoltan; Hutton, Sam

2013-02-01

According to the cold control theory of hypnosis (Dienes and Perner, 2007), hypnotic response occurs because of inaccurate higher order thoughts of intending. The dorsolateral prefrontal cortex (DLPFC) is a region likely involved in constructing accurate higher order thoughts. Thus, disrupting DLPFC with low frequency repetitive transcranial magnetic stimulation (rTMS) should make it harder to be aware of intending to perform an action. That is, it should be easier to respond to a hypnotic suggestion. Twenty-four medium hypnotisable subjects received low frequency rTMS to the left DLPFC and to a control site, the vertex, in counterbalanced order. The hypnotist was blind to which site had been stimulated. Subjects rated how strongly they expected to respond to each suggestion, and gave ratings on a 0-5 scale of the extent to which they experienced the response, for four suggestions (magnetic hands, arm levitation, rigid arm and taste hallucination). The experimenter also rated behavioural response. Low frequency rTMS to the DLPFC rather than vertex increased the degree of combined behavioural and subjective response. Further, subjects did not differ in their expectancy that they would respond in the two conditions, so the rTMS had an effect on hypnotic response above and beyond expectancies. The results support theories, including cold control theory, postulating a component of hypofrontality in hypnotic response. Copyright © 2012 Elsevier Ltd. All rights reserved.

Cancer Palliation: Layered Hypnotic Approaches Mending Symptoms, Minding Hope, and Meaning.

PubMed

Handel, Daniel L; Néron, Sylvain

2017-07-01

Advanced cancer often produces significant symptoms such as pain, anxiety, insomnia, nausea, and cachexia; many symptoms require medication adjustments in dose and route of administration, and most patients have significant symptom burdens near the end of life. Treatment strategies that integrate mind-body approaches, such as hypnosis, to improve symptoms are increasingly being studied and utilized. The current article addresses the role for adjunctive hypnotic approaches to relieve suffering from pain and other symptoms, while fostering hope, even in the midst of advancing illness, similar to Snyder's (2002) metaphorical painting of "a personal rainbow of the mind" (p. 269). We describe specific clinical indications, technical modifications, and imagistic language used in formulating hypnotic suggestions in the face of illness progression. Furthermore, we specifically describe formulation of layered hypnotic suggestions with intent to intentionally weave suggestions to modify symptoms and link to suggestions to enhance hope and alter time perception. This approach offers the opportunity to transform an experience often defined by its losses to one in which hidden opportunities for growth and change emerge within this transitional life experience.

Age, Sex, and Dose Effects of Nonbenzodiazepine Hypnotics on Hip Fracture in Nursing Home Residents.

PubMed

Dore, David D; Zullo, Andrew R; Mor, Vincent; Lee, Yoojin; Berry, Sarah D

2018-04-01

The Food and Drug Administration recommends a reduced dose of nonbenzodiazepine hypnotics in women, yet little is known about the age-, sex-, and dose-specific effects of these drugs on risk of hip fracture, especially among nursing home (NH) residents. We estimated the age-, sex-, and dose-specific effects of nonbenzodiazepine hypnotics on the rate of hip fracture among NH residents. Case-crossover study in US NHs. A total of 691 women and 179 men with hip fracture sampled from all US long-stay NH residents. Measures of patient characteristics were obtained from linked Medicare and the Minimum Data Set (2007-2008). The outcome was hospitalization for hip fracture with surgical repair. We estimated rate ratios (RRs) and 95% confidence intervals (CIs) from conditional logistic regression models for nonbenzodiazepine hypnotics (vs nonuse) comparing 0 to 29 days before hip fracture (hazard period) with 60 to 89 and 120 to 149 days before hip fracture (control periods). We stratified analyses by age, sex, and dose. The average RR of hip fracture was 1.7 (95% CI 1.5-1.9) for any use. The RR of hip fracture was higher for residents aged ≥90 years vs <70 years (2.2 vs 1.3); however, the CIs overlapped. No differences in the effect of the hypnotic on risk of hip fracture were evident by sex. Point estimates for hip fracture were greater with high-dose versus low-dose hypnotics (RR 1.9 vs 1.6 for any use), but these differences were highly compatible with chance. The rate of hip fracture in NH residents due to use of nonbenzodiazepine hypnotics was greater among older patients than among younger patients and, possibly, with higher doses than with lower doses. When clinicians are prescribing a nonbenzodiazepine hypnotic to any NH resident, doses of these drugs should be kept as low as possible, especially among those with advanced age. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Hypnotic color blindness and performance on the Stroop test.

PubMed

Mallard, D; Bryant, R A

2001-10-01

A suggestion for hypnotic color blindness was investigated by administering a reverse Stroop color-naming task. Prior to the suggestion for color blindness, participants learned associations between color names and shapes. Following the color blindness suggestion, participants were required to name the shapes when they appeared in colors that were either congruent or incongruent with the learned associations. The 18 high hypnotizable participants who passed the suggestion were slower to name (a) shapes in which the color name was incongruent with the color in which it was printed, (b) "unseen" rather than "seen" shapes, and (c) color-incongruent shapes that were printed in the color in which they were "color-blind." These patterns are discussed in terms of potential cognitive and social mechanisms that may mediate responses to hypnotic color blindness.

Hypnotics use but not insomnia increased the risk of dementia in traumatic brain injury patients.

PubMed

Chiu, Hsiao-Yean; Lin, En-Yuan; Wei, Li; Lin, Jiann-Her; Lee, Hsin-Chien; Fan, Yen-Chun; Tsai, Pei-Shan

2015-12-01

This study was intended to determine whether the use of hypnotics is associated with dementia in traumatic-brain-injury (TBI) patients. Data retrieved from the Longitudinal Health Insurance Database 2000. TBI patients who received a diagnosis of insomnia at 2 or more independent examinations after the index date of TBI were included. The comparison cohort consisted of randomly selected TBI patients who were matched to insomnia cohort patients based on sex and age. The 2 cohorts of TBI patients were subsequently divided into the following 4 study groups: hypnotics users with insomnia (TBI-IH, N=599), insomniacs who did not use hypnotics (TBI-I, N=931), hypnotics users without insomnia (TBI-H, N=199), and people without insomnia who did not use hypnotics (TBI-C, N=4271). Cox proportional-hazards regression models were used to determine the difference in dementia-free survival among the 4 study groups, after adjusting for the propensity score. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the TBI-IH and TBI-H groups showed that they had a higher risk of dementia (aHRs: 1.86 and 3.98; 95% CIs: 1.15-3.00 and 2.44-6.47, respectively), compared with that of the TBI-C group. However, the risk of dementia in the TBI-I group was not significantly different from that of the TBI-C group (aHR: 1.36; 95% CI: 0.85-2.19). This study suggests that the use of hypnotics is associated with an increased risk of dementia in TBI patients with or without insomnia, whereas insomnia alone is not. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Sleep quality, use of hypnotics and sleeping habits in different age-groups among older people.

PubMed

Hägg, Miriam; Houston, Britta; Elmståhl, Sölve; Ekström, Henrik; Wann-Hansson, Christine

2014-12-01

Sleep disturbances are common among older people (>65 years). Further, long-term use of sedative hypnoticsin older people is associated with morbidity and mortality. However, older people represent a large span of life years, and few studies have included the oldest-old above 85 years. To investigate and compare sleep quality, use of hypnotics and sleeping habits in different age groups of the older population in the Scania region, Sweden and in relation to sociodemographic- and functional status. A cross-sectional population-based study including 2931 people aged 60-93 years from five different municipalities in Scania was performed during 2001-2004. The sample was divided into age groups, young old (60-72 years), old-old (78-84 years) and oldest-old (87-93) years. Data constitutes of sleep related questions, sociodemographic- and functional status from the study 'Good Ageing in Skane'. Descriptive statistics were used to describe sleep quality, hypnotics use and sleeping habitsin relation to sociodemographic- and functional status. The aim was to investigate associations, not the magnitude of associations between variables. In all age groups, those who used hypnotics and were living alone had significantly poorer sleep quality and shortest sleeping time than nonhypnotic users and those who lived together. A significant increase of hypnotics and frequency of use was seen with increasing age. Frequency of napping increased significantly with degree of dependence in all age groups and with increasing age. Insomnia is still a problem and hypnotic use has not improved sleep for a large number of older people. Hypnotics are effective as short-term treatment, however, nonpharmacological interventions and psychological and behavioural therapies should be considered for treating older people with chronic insomnia.

Alert Hypnotic Inductions: Use in Treating Combat Post-Traumatic Stress Disorder.

PubMed

Eads, Bruce; Wark, David M

2015-10-01

Alert hypnosis can be a valuable part of the treatment protocol for the resolution of post-traumatic stress disorder (PTSD). Research indicates that combat veterans with PTSD are more hypnotically susceptible than the general population. For that reason, it is hypothesized that they should be better able to use hypnosis in treatment. As opposed to the traditional modality, eyes-open alert hypnosis allows the patient to take advantage of hypnotic phenomena while participating responsibly in work, social life, and recreation. Three case studies are reported on combat veterans with PTSD who learned to overcome their symptoms using alert hypnosis.

Effect-site concentrations of remifentanil causing bradycardia in hypnotic and non-hypnotic patients.

PubMed

Hayashi, Kazuko; Tanaka, Akiko

2016-12-01

Although the induction of anaesthesia with remifentanil often causes bradycardia, the relationship between the effect-site concentration (Ce) of remifentanil and instantaneous heart rate (HR) has remained unclear. The present study examined the relationship between instantaneous HR and remifentanil Ce at the induction of anaesthesia with and without propofol hypnosis, to facilitate safe management of anaesthesia induction with remifentanil. Instantaneous HR was calculated every 5 s using an electrocardiographic real-time analysis system (MemCalc/Makin2; GMS, Tokyo, Japan). At the beginning of anaesthesia induction, continuous infusion of remifentanil (1 μg min -1  kg -1 ) preceded hypnosis with propofol in 13 patients [non-hypnosis group; mean age, 67.8 (17.5) years], while propofol bolus (30-50 mg) was injected together with continuous remifentanil medication in 18 patients [hypnosis group; mean age, 62.9 (16.5) years]. Remifentanil Ce was estimated every 5 s using the three-compartment model proposed by Minto et al. and the relationship between estimated remifentanil Ce and instantaneous HR was examined. In the hypnosis group, HR was significantly lower than basal HR when remifentanil Ce was increased to 3.5 ng ml -1 (p < 0.05), whereas no significant HR reduction was found in the non-hypnosis group until remifentanil Ce reached >5 ng ml -1 (p < 0.05). The induction of anaesthesia using remifentanil with propofol hypnotics significantly reduces HR even in a low remifentanil Ce insufficient to suppress the cardiovascular response at tracheal intubation. Preparations to treat bradycardia are recommended for the safe management of anaesthesia induction when remifentanil is combined with hypnotics.

Personality Disorder Features and Insomnia Status amongst Hypnotic-Dependent Adults

PubMed Central

Ruiter, Megan E.; Lichstein, Kenneth L.; Nau, Sidney D.; Geyer, James

2012-01-01

Objective To determine the prevalence of personality disorders and their relation to insomnia parameters among persons with chronic insomnia with hypnotic dependence. Methods Eighty-four adults with chronic insomnia with hypnotic dependence completed the SCID-II personality questionnaire, two-weeks of sleep diaries, polysomnography, and measures of insomnia severity, impact, fatigue severity, depression, anxiety, and quality of life. Frequencies, between-subjects t-tests and hierarchical regression models were conducted. Results Cluster C personality disorders were most prevalent (50%). Obsessive-compulsive personality disorder (OCPD) was most common (n=39). These individuals compared to participants with no personality disorders did not differ in objective and subjective sleep parameters. Yet, they had poorer insomnia-related daytime functioning. OCPD and Avoidant personality disorders features were associated with poorer daytime functioning. OCPD features were related to greater fatigue severity, and overestimation of time awake was trending. Schizotypal and Schizoid features were positively associated with insomnia severity. Dependent personality disorder features were related to underestimating time awake. Conclusions Cluster C personality disorders were highly prevalent in patients with chronic insomnia with hypnotic dependence. Features of Cluster C and A personality disorders were variously associated with poorer insomnia-related daytime functioning, fatigue, and estimation of nightly wake-time. Future interventions may need to address these personality features. PMID:22938862

Personality disorder features and insomnia status amongst hypnotic-dependent adults.

PubMed

Ruiter, Megan E; Lichstein, Kenneth L; Nau, Sidney D; Geyer, James D

2012-10-01

To determine the prevalence of personality disorders and their relation to insomnia parameters among persons with chronic insomnia with hypnotic dependence. Eighty-four adults with chronic insomnia with hypnotic dependence completed the SCID-II personality questionnaire, two-weeks of sleep diaries, polysomnography, and measures of insomnia severity, impact, fatigue severity, depression, anxiety, and quality of life. Frequencies, between-subjects t-tests and hierarchical regression models were conducted. Cluster C personality disorders were most prevalent (50%). Obsessive-Compulsive personality disorder (OCPD) was most common (n=39). These individuals compared to participants with no personality disorders did not differ in objective and subjective sleep parameters. Yet, they had poorer insomnia-related daytime functioning. OCPD and Avoidant personality disorders features were associated with poorer daytime functioning. OCPD features were related to greater fatigue severity, and overestimation of time awake was trending. Schizotypal and Schizoid features were positively associated with insomnia severity. Dependent personality disorder features were related to underestimating time awake. Cluster C personality disorders were highly prevalent in patients with chronic insomnia with hypnotic dependence. Features of Cluster C and A personality disorders were variously associated with poorer insomnia-related daytime functioning, fatigue, and estimation of nightly wake-time. Future interventions may need to address these personality features. Copyright © 2012 Elsevier B.V. All rights reserved.

Oxytocin impedes the effect of the word blindness post-hypnotic suggestion on Stroop task performance.

PubMed

Parris, Benjamin A; Dienes, Zoltan; Bate, Sarah; Gothard, Stace

2014-07-01

The ability to enhance sensitivity to relevant (post)hypnotic suggestions has implications for creating clinically informed analogues of psychological and neuropsychological conditions and for the use of hypnotic interventions in psychological and medical conditions. The aim of this study was to test the effect of oxytocin inhalation on a post-hypnotic suggestion that previously has been shown to improve the selectivity of attention in the Stroop task. In a double-blind placebo-controlled between-subjects study, medium hypnotizable individuals performed the Stroop task under normal conditions and when they had been given a post-hypnotic suggestion that they would perceive words as meaningless symbols. In line with previous research, Stroop interference was substantially reduced by the suggestion in the placebo condition. However, contrary to expectations, oxytocin impeded the effect of the word blindness suggestion on performance. The results are explained in terms of the requirement for the re-implementation of the word blindness suggestion on a trial-by-trial basis and the need to sustain activation of the suggestion between trials. The findings contrast with a recent study showing a beneficial effect of oxytocin on sensitivity to (post)hypnotic suggestions but are consistent with findings showing a detrimental effect of oxytocin on memory processes. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Mirror agnosia and the mirrored-self misidentification delusion: a hypnotic analogue.

PubMed

Connors, Michael H; Cox, Rochelle E; Barnier, Amanda J; Langdon, Robyn; Coltheart, Max

2012-05-01

Mirrored-self misidentification is the delusional belief that one's reflection in the mirror is a stranger. Current theories suggest that one pathway to the delusion is mirror agnosia (a deficit in which patients are unable to use mirror knowledge when interacting with mirrors). This study examined whether a hypnotic suggestion for mirror agnosia can recreate features of the delusion. Ten high hypnotisable participants were given either a suggestion to not understand mirrors or to see the mirror as a window. Participants were asked to look into a mirror and describe what they saw. Participants were tested on their understanding of mirrors and received a series of challenges. Participants then received a detailed postexperimental inquiry. Three of five participants given the suggestion to not understand mirrors reported seeing a stranger and maintained this belief when challenged. These participants also showed signs of mirror agnosia. No participants given the suggestion to see a window reported seeing a stranger. Results indicate that a hypnotic suggestion for mirror agnosia can be used to recreate the mirrored-self misidentification delusion. Factors influencing the effectiveness of hypnotic analogues of psychopathology, such as participants' expectations and interpretations, are discussed.

Benzodiazepine-like hypnotics and the associated risk of road traffic accidents.

PubMed

Orriols, L; Philip, P; Moore, N; Castot, A; Gadegbeku, B; Delorme, B; Mallaret, M; Lagarde, E

2011-04-01

The aim of the study was to investigate the association between the use of benzodiazepine or benzodiazepine-like hypnotics and the risk of road traffic accidents. Data from three French national databases were matched: the health-care insurance database, police reports, and the police database of injury-related traffic accidents. A total of 72,685 drivers involved in injury-related road traffic accidents in France, from 2005 to 2008, were included in the study. The risk of being responsible for a traffic accident was higher in users of benzodiazepine hypnotics (odds ratio (OR) = 1.39 (1.08-1.79)) and in the 155 drivers to whom a dosage of more than one pill of zolpidem a day had been dispensed during the 5 months before the collision (OR = 2.46 (1.70-3.56)). No association was found between the use of zopiclone and risk of traffic accidents. Although this study did not find any association between the use of zolpidem as recommended and causation of traffic accidents, the potential risk related to possible abuse of the drug and risky driving behaviors should be further investigated. The results related to benzodiazepine hypnotics are consistent with those of previous studies.

Are You Suggesting That's My Hand? The Relation Between Hypnotic Suggestibility and the Rubber Hand Illusion.

PubMed

Walsh, E; Guilmette, D N; Longo, M R; Moore, J W; Oakley, D A; Halligan, P W; Mehta, M A; Deeley, Q

2015-01-01

Hypnotic suggestibility (HS) is the ability to respond automatically to suggestions and to experience alterations in perception and behavior. Hypnotically suggestible participants are also better able to focus and sustain their attention on an experimental stimulus. The present study explores the relation between HS and susceptibility to the rubber hand illusion (RHI). Based on previous research with visual illusions, it was predicted that higher HS would lead to a stronger RHI. Two behavioral output measures of the RHI, an implicit (proprioceptive drift) and an explicit (RHI questionnaire) measure, were correlated against HS scores. Hypnotic suggestibility correlated positively with the implicit RHI measure contributing to 30% of the variation. However, there was no relation between HS and the explicit RHI questionnaire measure, or with compliance control items. High hypnotic suggestibility may facilitate, via attentional mechanisms, the multisensory integration of visuoproprioceptive inputs that leads to greater perceptual mislocalization of a participant's hand. These results may provide insight into the multisensory brain mechanisms involved in our sense of embodiment.

Consumer hypnotic-like suggestibility: possible mechanism in compulsive purchasing.

PubMed

Prete, M Irene; Guido, Gianluigi; Pichierri, Marco

2013-08-01

The authors hypothesize a concept, Consumer Hypnotic-Like Suggestibility (CHLS), defined as an altered state of consciousness, as a state causing a tendency to respond positively to messages aimed at inducing consumers to make unplanned purchases. This study aims to investigate the associations of CHLS with interpersonal variables and compulsive purchasing--a frequent and uncontrollable preoccupation with buying or impulses to buy. A study was conducted on a sample of 232 subjects (n = 111 men; M age = 41 yr.), through the administration of a questionnaire, which measured: CHLS, compulsive purchasing, consumer susceptibility to interpersonal influence (the necessity to enhance one's image in the opinion of others through the consumption of products), and consumer atmospherics, i.e., environmental stimuli known to influence purchasing decisions. Modeling and mediation analyses suggested that internal and external drivers--Consumer Susceptibility to Interpersonal Influence and atmospherics--are positively related to CHLS which affects compulsive purchasing.

Self-mutilating behavior in patients with dissociative disorders: the role of innate hypnotic capacity.

PubMed

Ebrinc, Servet; Semiz, Umit B; Basoglu, Cengiz; Cetin, Mesut; Agargun, Mehmet Y; Algul, Ayhan; Ates, Alpay

2008-01-01

Despite the fact that the assumption of a relationship between self-mutilation and dissociative disorders (DD) has a long history, there is little empirical evidence to support this premise. The present study examined this relationship and investigated whether this commonality is associated with innate hypnotic capacity. Fifty patients diagnosed with DD and 50 control subjects with major depression were assessed by using a self-mutilation questionnaire, Dissociative Experiences Scale, Traumatic Experiences Checklist, and the Eye-Roll Sign for their self-mutilating behaviors, dissociative symptoms, early trauma, and innate hypnotic capacity, respectively. We have found that 82% of the present sample of patients with DD injured themselves. They had higher scores on trauma, dissociation and eye-roll measurements than controls. In addition, DD patients with self-mutilation were more likely to have high scores of trauma, dissociation and eye-roll than those without self-mutilation. Innate hypnotic capacity was a strong predictor of self-mutilating behavior in DD patients. This study strongly supports the assumption that patients with DD are at high risk for self-mutilating behavior and points to the necessity of routine screening for self-mutilating behavior as well as the hypnotic capacity which may constitute a high risk for self-injury in this patient group.

Chaos-chaos transition of left hemisphere EEGs during standard tasks of Waterloo-Stanford Group Scale of hypnotic susceptibility.

PubMed

Yargholi, Elahe'; Nasrabadi, Ali Motie

2015-01-01

A recent study, recurrence quantification analysis of EEG signals during standard tasks of Waterloo-Stanford Group Scale of hypnotic susceptibility investigated recurrence quantifiers (RQs) of hypnotic electroencephalograph (EEG) signals recorded after hypnotic induction while subjects were doing standard tasks of Waterloo-Stanford Group Scale (WSGS) of hypnotic susceptibility to distinguish subjects of different hypnotizability levels. Following the same analysis, the current study determines the capability of different RQs to distinguish subjects of low, medium and high hypnotizability level and studies the influence of hypnotizability level on underlying dynamic of tasks. Besides, EEG channels were sorted according to the number of their RQs, which differed significantly among subjects of different hypnotizability levels. Another valuable result was determination of major brain regions in observing significant differences in various task types (ideomotors, hallucination, challenge and memory).

Effects of hypnotic bromovalerylurea on microglial BV2 cells.

PubMed

Kawasaki, Shun; Abe, Naoki; Ohtake, Fumito; Islam, Afsana; Choudhury, Mohammed Emamussalehin; Utsunomiya, Ryo; Kikuchi, Satoshi; Nishihara, Tasuku; Kuwabara, Jun; Yano, Hajime; Watanabe, Yuji; Aibiki, Mayuki; Yorozuya, Toshihiro; Tanaka, Junya

2017-06-01

An old sedative and hypnotic bromovalerylurea (BU) has anti-inflammatory effects. BU suppressed nitric oxide (NO) release and proinflammatory cytokine expression by lipopolysaccharide (LPS)-treated BV2 cells, a murine microglial cell line. However, BU did not inhibit LPS-induced nuclear translocation of nuclear factor-κB and subsequent transcription. BU suppressed LPS-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppressed the NO release much more weakly than that of BU, although filgotinib almost completely prevented LPS-induced STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 did not affect the suppressive effects of BU on LPS-induced NO release by BV2 cells. A combination of BU and filgotinib synergistically suppressed the NO release. The mitochondrial complex I inhibitor rotenone, which did not prevent STAT1 phosphorylation or IRF1 expression, suppressed proinflammatory mediator expression less significantly than BU. BU and rotenone reduced intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppressed NO release by LPS-treated BV2 cells as strongly as BU. These results suggest that anti-inflammatory actions of BU may be attributable to the synergism of inhibition of JAK1/STAT1-dependent pathways and reduction in iATP level. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Reassessment of hypnotic symptom removal by Freud and Bernheim.

PubMed

Ball, Thomas S

2006-10-01

As demonstrations of clinical efficacy, cases reported by Freud and Bernheim reveal an intrinsic advantage of hypnotic symptom removal over therapies requiring extended periods to achieve significant outcomes. They also lend support to Weitzenhoffer's survey of therapeutic results achieved during the classical (pre-1900) period.

Hypnotic susceptibility and affective states in bipolar I and II disorders.

PubMed

Zhang, Bingren; Wang, Jiawei; Zhu, Qisha; Ma, Guorong; Shen, Chanchan; Fan, Hongying; Wang, Wei

2017-11-09

Highly hypnotizable individuals have impaired executive function, elevated motor impulsivity and increased emotional sensitivity, which are sometimes found in bipolar disorder patients. It is then reasonable to assume that certain aspects of hypnotic susceptibility differ with the types of bipolar disorder. The Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) test, the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32) and the Plutchick-van Praag Depression Inventory (PVP) were applied to 62 patients with bipolar I disorder, 33 bipolar II disorder, and 120 healthy volunteers. The passing rate of the SHSS:C 'Moving hands apart' item was higher in bipolar I patients than in controls, whereas for 'Mosquito hallucination' the rate was lower. Bipolar I and II patients scored significantly higher on MDQ, HCL-32 and PVP scales than controls. The passing rates of 'Mosquito hallucination' in controls, 'Arm rigidity' in bipolar I, and 'Age regression' in bipolar II predicted the respective MDQ scores. In contrast to cognitive suggestions, bipolar I patients followed motor suggestions more often under hypnosis. Furthermore, both bipolar disorder patients and healthy volunteers demonstrated associations between mania levels and certain hypnotic susceptibility features. Our study aids in better understanding the altered conscious states in bipolar disorders, and encourages the use of related psychotherapy for these patients.

Study of Sedative-Hypnotic Effects of Aloe vera L. Aqueous Extract through Behavioral Evaluations and EEG Recording in Rats

PubMed Central

Abdollahnejad, Fatemeh; Mosaddegh, Mahmoud; Nasoohi, Sanaz; Mirnajafi-Zadeh, Javad; Kamalinejad, Mohammad; Faizi, Mehrdad

2016-01-01

In this study, we investigated the sedative and hypnotic effects of the aqueous extract of Aloe vera on rats. In order to evaluate the overall hypnotic effects of the Aloe vera extract, open field and loss of righting reflex tests were primarily used. The sedative and hypnotic effects of the extract were then confirmed by detection of remarkable raise in the total sleeping time through analysis of electroencephalographic (EEG) recordings of animals. Analysis of the EEG recordings showed that there is concomitant change in Rapid Eye Movement (REM) and None Rapid Eye Movement (NREM) sleep in parallel with the prolonged total sleeping time. Results of the current research show that the extract has sedative-hypnotic effects on both functional and electrical activities of the brain. PMID:27610170

Hypnotic clever hands: Agency and automatic responding.

PubMed

Polito, Vince; Barnier, Amanda J; Connors, Michael H

2018-06-01

The Clever Hands task (Wegner, Fuller, & Sparrow, 2003) is a behavioral illusion in which participants make responses to a trivia quiz for which they have no sense of agency. Sixty high hypnotizable participants completed two versions of the Clever Hands task. Quiz One was a replication of the original study. Quiz Two was a hypnotic adaptation using three suggestions that were based on clinical disruptions to the sense of agency. The suggestions were for: random responding, thought insertion, and alien control. These suggestions led to differences in accuracy (action production) and estimates of accuracy (action projection). Specifically, whereas the random responding suggestion had little effect, the two clinically based suggestions had opposite impacts on action production: the thought insertion suggestion led to an increase in the rate of correct responses (although participants still believed they were responding randomly); while the alien control suggestion led to a reduction in the rate of correct answers and a pattern of results that more closely approximated randomness. Contrary to theoretical accounts that claim that hypnosis affects executive monitoring rather than executive control, this result indicates that specific hypnotic suggestions can also influence the implicit processes involved in action production. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Relationship between hypnosis and personality trait in participants with high or low hypnotic susceptibility

PubMed Central

Zhang, Yingchun; Wang, Yunke; Shen, Chanchan; Ye, Yingying; Shen, Si; Zhang, Bingren; Wang, Jiawei; Chen, Wei; Wang, Wei

2017-01-01

Background The relationship between normal personality and hypnotic susceptibility is important for understanding mental processing and mental disorders, but it is less consistent in normal people or in patients with a psychiatric disorder. We have hypothesized that the correlation exists but varies in individuals with different levels of hypnotizability. Participants and methods We invited 72 individuals with high (HIGH group) and 47 individuals with low (LOW group) hypnotic susceptibilities to undertake tests of NEO-PI-R and the Stanford Hypnotic Susceptibility Scale, Form C (SHSSC). Results The HIGH group scored significantly higher than the LOW group did on openness to experience and its facet openness to feelings. In the LOW group, SHSSC total was positively predicted by openness to ideas; age regression was positively predicted by openness to experience and negatively predicted by extraversion; anosmia to ammonia was negatively predicted by agreeableness; and negative visual hallucination was positively predicted by openness to experience. In the HIGH group, hallucinated voice was positively predicted by openness to experience and negatively predicted by agreeableness, and posthypnotic amnesia was positively predicted by extraversion and negatively predicted by openness to experience. Conclusion The associations between normal personality traits and hypnotic susceptibility items were weak and different in the two groups, which imply that managing mental or somatoform disorders might be through adjusting hypnotizability and mobilizing personality functions. PMID:28435270

Concurrent Use of Hypnotic Drugs and Chinese Herbal Medicine Therapies among Taiwanese Adults with Insomnia Symptoms: A Population-Based Study.

PubMed

Lee, Kuei-Hua; Tsai, Yueh-Ting; Lai, Jung-Nien; Lin, Shun-Ku

2013-01-01

Background. The increased practice of traditional Chinese medicine (TCM) worldwide has raised concerns regarding herb-drug interactions. The purpose of our study is to analyze the concurrent use of Chinese herbal products (CHPs) among Taiwanese insomnia patients taking hypnotic drugs. Methods. The usage, frequency of services, and CHP prescribed among 53,949 insomnia sufferers were evaluated from a random sample of 1 million beneficiaries in the National Health Insurance Research Database. A logistic regression method was used to identify the factors that were associated with the coprescription of a CHP and a hypnotic drug. Cox proportional hazards regressions were performed to calculate the hazard ratios (HRs) of hip fracture between the two groups. Results. More than 1 of every 3 hypnotic users also used a CHP concurrently. Jia-Wei-Xiao-Yao-San (Augmented Rambling Powder) and Suan-Zao-Ren-Tang (Zizyphus Combination) were the 2 most commonly used CHPs that were coadministered with hypnotic drugs. The HR of hip fracture for hypnotic-drug users who used a CHP concurrently was 0.57-fold (95% CI = 0.47-0.69) that of hypnotic-drug users who did not use a CHP. Conclusion. Exploring potential CHP-drug interactions and integrating both healthcare approaches might be beneficial for the overall health and quality of life of insomnia sufferers.

Mind styles and the hypnotic induction profile: measure and match to enhance medical treatment.

PubMed

Greenleaf, Marcia

2006-07-01

Modern medical technology and economic impositions tend to dehumanize the medical patient. This paper describes a targeted use of the hypnotic modality for relationship building, symptom management, and restoring a sense of self to the patient. To humanize medical care one patient at a time, examples are given for the use of the Hypnotic Induction Profile, the Eye Roll sign and AOD (Apollonian-Odyssean-Dionysian) Mind-Style Questionnaire as a basis for choosing bio-psycho-social treatment strategies. This trio of assessments can be used together, in approximately 10 to 15 minutes, or separately, if treatment decisions need to be made in a few minutes or less. The hypothesis presented is that matching treatment strategies, with or without formal hypnosis, to hypnotic capacity and mind style can increase respectful care and efficacy of treatment outcome. Clinical examples will illustrate this approach to enhance recovery, morale, and maximize patients' ability to become active partners on their own behalf.

Dispositional mindfulness, anticipation and abstinence symptoms related to hypnotic dependence among insomniac women who seek treatment: A cross-sectional study.

PubMed

Barros, Víviam Vargas; Opaleye, Emérita Sátiro; Demarzo, Marcelo; Bowen, Sarah; Curado, Daniela Fernández; Hachul, Helena; Noto, Ana Regina

2018-01-01

Dispositional mindfulness can be described as the mental ability to pay attention to the present moment, non-judgmentally. There is evidence of inverse relation between dispositional mindfulness and insomnia and substance use, but as of yet, no studies evaluating the specific association between dispositional mindfulness and the components of hypnotic use disorder. To evaluate the association between dispositional mindfulness and the components of dependence among female chronic hypnotic users. Seventy-six women, chronic users of hypnotics, who resorted to Mindfulness-Based Relapse Prevention for the cessation of hypnotic use were included in the study. The Five Facet Mindfulness Questionnaire (FFMQ) evaluated the levels and facets of mindfulness, and the subscales of the Benzodiazepine Dependence Questionnaire (BENDEP) assessed dependence on hypnotics. We also evaluated sociodemographic variables and symptoms of insomnia and anxiety. The associations between the FFMQ facets and the BENDEP subscales were evaluated with binomial logistic regression, adjusted for income, schooling, anxiety, and insomnia. We observed associations between facets of the FFMQ and specific aspects of hypnotic dependence. The facet "observing" was inversely associated with the "concern about lack of availability of the hypnotic" [aOR = 0.87 95% CI (0.79-0.97)], and the facet "non-reacting to inner experience" with "noncompliance with the prescription recommendations" [aOR = 0.86 95% CI (0.75-0.99)]. The total score of the FFMQ was inversely associated to those two dependence subscales [aOR = 0.94 95% CI (0.89-0.99)]. "Observing" and "non-reactivity to inner experience" were also inversely associated with the "impairments related to the withdrawal symptoms" [aOR = 0.84 95% CI (0.73-0.97)] and [aOR = 0.78 95% CI (0.63-0.96)], respectively. The FFMQ was not associated with "awareness of problematic hypnotic use". Dispositional mindfulness, specifically the facets "observing" and "non

Crime, hysteria and belle époque hypnotism: the path traced by Jean-Martin Charcot and Georges Gilles de la Tourette.

PubMed

Bogousslavsky, Julien; Walusinski, Olivier; Veyrunes, Denis

2009-01-01

Hysteria and hypnotism became a favorite topic of studies in the fin de siècle neurology that emerged from the school organized at La Salpêtrière by Jean-Martin Charcot, where he had arrived in 1861. Georges Gilles de la Tourette started working with Charcot in 1884 and probably remained his most faithful student, even after his mentor's death in 1893. This collaboration was particularly intense on 'criminal hypnotism', an issue on which Hippolyte Bernheim and his colleagues from the Nancy School challenged the positions taken by the Salpêtrière School. Bernheim claimed that hypnotism was not a diagnostic feature of hysteria and that there were real-life examples of murders suggested under hypnosis, while hypnosis susceptibility was identified with hysteria by Charcot and Gilles de la Tourette, who saw rape as the only crime associated with hypnotism. The quarrel was particularly virulent during a series of famous criminal cases which took place between 1888 and 1890. At the time, it was considered that La Salpêtrière had succeeded over Nancy, since the role of hypnotism was discarded during these famous trials. However, the theories of Charcot and Gilles de la Tourette were also damaged by the fight, which probably triggered the conceptual evolution leading to Joseph Babinski's revision of hysteria in 1901. Gilles de la Tourette's strong and public interest in hypnotism nearly cost him his life, when a young woman who claimed to have been hypnotized against her will shot him in the head at his own home in 1893. It was subsequently shown that hypnotism had nothing to do with it. The delusional woman was interned at Sainte-Anne for mental disturbance, thus escaping trial. Ironically, Gilles de la Tourette may have been partly responsible, since he had been one of the strongest proponents of placing mentally-ill criminals in asylums instead of prisons. 2009 S. Karger AG, Basel

Zopiclone as a preoperative night hypnotic: a double-blind comparison with temazepam and placebo.

PubMed

Whitehead, C; Sanders, L; Appadurai, I; Power, I; Rosen, M; Robinson, J

1994-04-01

We have examined the hypnotic effects of zopiclone 7.5 mg and temazepam 20 mg compared with placebo in a double-blind, randomized, clinical study of 60 patients on the night before operation. Evaluation was both subjective (visual analogue scales and a sleep questionnaire), to measure the quality of sleep, and objective (critical flicker fusion, object recall and paired associates tasks), to measure residual impairment. We found that zopiclone was an effective single-dose hypnotic with similar residual effects to the benzodiazepine and it may therefore provide a suitable alternative to benzodiazepines.

Postural instability and consequent falls and hip fractures associated with use of hypnotics in the elderly: a comparative review.

PubMed

Allain, Hervé; Bentué-Ferrer, Danièle; Polard, Elisabeth; Akwa, Yvette; Patat, Alain

2005-01-01

The aim of this review is to establish the relationship between treatment with hypnotics and the risk of postural instability and as a consequence, falls and hip fractures, in the elderly. A review of the literature was performed through a search of the MEDLINE, Ingenta and PASCAL databases from 1975 to 2005. We considered as hypnotics only those drugs approved for treating insomnia, i.e. some benzodiazepines and the more recently launched 'Z'-compounds, i.e. zopiclone, zolpidem and zaleplon. Large-scale surveys consistently report increases in the frequency of falls and hip fractures when hypnotics are used in the elderly (2-fold risk). Benzodiazepines are the major class of hypnotics involved in this context; falls and fractures in patients taking Z-compounds are less frequently reported, and in this respect, zolpidem is considered as at risk in only one study. It is important to note, however, that drug adverse effect relationships are difficult to establish with this type of epidemiological data-mining. On the other hand, data obtained in laboratory settings, where confounding factors can be eliminated, prove that benzodiazepines are the most deleterious hypnotics at least in terms of their effects on body sway. Z-compounds are considered safer, probably because of their pharmacokinetic properties as well as their selective pharmacological activities at benzodiazepine-1 (BZ(1)) receptors. The effects of hypnotics on balance, gait and equilibrium are the consequence of differential negative impacts on vigilance and cognitive functions, and are highly dose- and time-dependent. Z-compounds have short half-lives and have less cognitive and residual effects than older medications. Some practical rules need to be followed when prescribing hypnotics in order to prevent falls and hip fractures as much as possible in elderly insomniacs, whether institutionalised or not. These are: (i) establish a clear diagnosis of the sleep disorder; (ii) take into account chronic

Hypnotics and the Occurrence of Bone Fractures in Hospitalized Dementia Patients: A Matched Case-Control Study Using a National Inpatient Database.

PubMed

Tamiya, Hiroyuki; Yasunaga, Hideo; Matusi, Hiroki; Fushimi, Kiyohide; Ogawa, Sumito; Akishita, Masahiro

2015-01-01

Preventing falls and bone fractures in hospital care is an important issue in geriatric medicine. Use of hypnotics is a potential risk factor for falls and bone fractures in older patients. However, data are lacking on the association between use of hypnotics and the occurrence of bone fracture. We used a national inpatient database including 1,057 hospitals in Japan and included dementia patients aged 50 years or older who were hospitalized during a period of 12 months between April 2012 and March 2013. The primary outcome was the occurrence of bone fracture during hospitalization. Use of hypnotics was compared between patients with and without bone fracture in this matched case-control study. Of 140,494 patients, 830 patients suffered from in-hospital fracture. A 1:4 matching with age, sex and hospital created 817 cases with fracture and 3,158 matched patients without fracture. With adjustment for the Charlson comorbidity index, emergent admission, activities of daily living, and scores for level walking, a higher occurrence of fractures were seen with short-acting benzodiazepine hypnotics (odds ratio, 1.43; 95% confidence interval, 1.19-1.73; P<0.001), ultrashort-acting non-benzodiazepine hypnotics (1.66; 1.37-2.01; P<0.001), hydroxyzine (1.45; 1.15-1.82, P=0.001), risperidone and perospirone (1.37; 1.08-1.73; P=0.010). Other drug groups were not significantly associated with the occurrence of in-hospital fracture. Short-acting benzodiazepine hypnotics and ultrashort-acting non-benzodiazepine hypnotics may increase risk of bone fracture in hospitalized dementia patients.

Next-day residual effects of hypnotics in DSM-IV primary insomnia: a driving simulator study with simultaneous electroencephalogram monitoring.

PubMed

Staner, Luc; Ertlé, Stéphane; Boeijinga, Peter; Rinaudo, Gilbert; Arnal, Marie Agnès; Muzet, Alain; Luthringer, Rémy

2005-10-01

Most studies that investigated the next-day residual effects of hypnotic drugs on daytime driving performances were performed on healthy subjects and after a single drug administration. In the present study, we further examine whether the results of these studies could be generalised to insomniac patients and after repeated drug administration. Single and repeated (7 day) doses of zolpidem (10 mg), zopiclone (7.5 mg), lormetazepam (1 mg) or placebo were administered at bedtime in a crossover design to 23 patients (9 men and 14 women aged 38.8+/-2.0 years) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) primary insomnia. Driving tests were performed 9-11 h post-dose. Results showed that treatment effects were evidenced for subjective sleep, for driving abilities, and for electroencephalogram (EEG) recorded before (resting EEG) and during the driving simulation test (driving EEG). Compared to placebo, zopiclone increased the number of collisions and lormetazepam increased deviation from speed limit and deviation from absolute speed, whereas zolpidem did not differentiate from placebo on these analyses. EEG recordings showed that in contrast to zolpidem, lormetazepam and zopiclone induced typical benzodiazepine-like alterations, suggesting that next-day poor driving performance could relate to a prolonged central nervous system effect of these two hypnotics. The present results corroborate studies on healthy volunteers showing that residual effects of hypnotics increase with their half-lives. The results further suggest that drugs preserving physiological EEG rhythms before and during the driving simulation test 9-11 h post-dose, such as zolpidem, do not influence next-day driving abilities.

The Impact of Hypnotic Suggestions on Reaction Times in Continuous Performance Test in Adults with ADHD and Healthy Controls

PubMed Central

Virta, Maarit; Hiltunen, Seppo; Mattsson, Markus; Kallio, Sakari

2015-01-01

Attention is one of the key factors in both hypnotic processes and patients with ADHD. In addition, the brain areas associated with hypnosis and ADHD overlap in many respects. However, the use of hypnosis in ADHD patients has still received only minor attention in research. The main purpose of the present work was to investigate whether hypnosis and hypnotic suggestions influence the performance of adult ADHD (n = 27) and control participants (n = 31) in the continuous performance test (CPT). The hypnotic susceptibility of the participants was measured by the Harvard Group Scale of Hypnotic Susceptibility (HGSHS:A) and the attentional task was a three minute long auditory version of the CPT. The CPT task was administered four times: before hypnosis (CPT1), after a hypnotic induction (CPT2), after suggestions about speed and accuracy (CPT3), and after the termination of hypnosis (CPT4). The susceptibility of the groups measured by HGSHS:A did not differ. There was a statistically significant decrease in reaction times in both ADHD and control groups between CPT2 and CPT3. The differences between CPT1 and CPT2, even though non-significant, were different in the two groups: in the ADHD group reaction times decreased whereas in the control group they increased. Both groups made very few errors in the short CPT. This study indicates that hypnotic suggestions have an effect on reaction times in the sustained attention task both in adult ADHD patients and control subjects. The theoretical and clinical implications are discussed. PMID:25962151

Differential frontal-parietal phase synchrony during hypnosis as a function of hypnotic suggestibility.

PubMed

Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

2011-10-01

Spontaneous dissociative alterations in awareness and perception among highly suggestible individuals following a hypnotic induction may result from disruptions in the functional coordination of the frontal-parietal network. We recorded EEG and self-reported state dissociation in control and hypnosis conditions in two sessions with low and highly suggestible participants. Highly suggestible participants reliably experienced greater state dissociation and exhibited lower frontal-parietal phase synchrony in the alpha2 frequency band during hypnosis than low suggestible participants. These findings suggest that highly suggestible individuals exhibit a disruption of the frontal-parietal network that is only observable following a hypnotic induction. Copyright © 2011 Society for Psychophysiological Research.

Hypnotics use in children 0-18 months: moderate agreement between mother-reported survey data and prescription registry data.

PubMed

Holdø, Ingvild; Bramness, Jørgen G; Handal, Marte; Torgersen, Leila; Reichborn-Kjennerud, Ted; Ystrøm, Eivind; Nordeng, Hedvig; Skurtveit, Svetlana

2017-01-01

Different methods in pharmacoepidemiology can be used to study hypnotic use in children. But neither questionnaire-based data nor prescription records can be considered a "gold standard". This study aimed to investigate the agreement between mother-reported questionnaire-based data and prescription record data for hypnotic drugs in children aged 0-18 months. The agreement was compared to the agreement for a group of antiepileptic drugs. Prescription record data were collected from the Norwegian prescription database for 47,413 children also surveyed in the Norwegian mother and child cohort between 2005 and 2009. Agreement between in the two data sources was calculated using Cohens Kappa. Multinomial logistic regression was used to calculate the effect of sociodemographic variables on discrepancies in data sources. The agreement between mother-reported and dispensed hypnotics was less than 50% for all hypnotics. Sensitivity of reporting increased with number of filled prescriptions. The agreement of antiepileptic drugs was 92.9% in the same population. Of several sociodemographic factors only paternal educational level and maternal work situation was significantly related to agreement between prescription record and survey data. There was a moderate agreement between reported use and dispensed hypnotic drugs for infants and toddlers. Results indicate that sociodemographic factors play only a minor role in explaining discrepancy.

Quality of life and social determinants of anxiolytics and hypnotics use in women in Poland: a population-based study.

PubMed

Zagozdzon, Pawel; Kolarzyk, Emilia; Marcinkowski, Jerzy T

2013-05-01

The majority of studies show a substantially higher consumption of anxiolytics and antidepressants among women than among men and in the age bracket above 45 years. To analyse association between the use of hypnotics/anxiolytics, and various characteristics of Polish women, including health-related quality of life. One thousand, five hundred and sixty (1,560) women aged 45-60 years completed a questionnaire dealing with the use of hypnotics/anxiolytics, demographic characteristics, environmental and work stress exposure, and self-reported quality of life (SF-36 form). The following variables were revealed as the predictors of hypnotic/anxiolytic use on univariate analysis: age; social pension; stress at work and environmental stress; hormone replacement therapy; headache; palpitations; mood swings or increased muscular tension; anger; duration of symptoms longer than one week; consulting a specialist; and low physical and mental health-related quality of life. The significant protective factors included: vocational and tertiary education; job satisfaction; and home as place of rest. The independent predictors of anxiolytic/hypnotic use included consulting a specialist and symptoms lasting more than one week, while job satisfaction and home as place of rest were the independent protective factors. The use of hypnotic/anxiolytic medication is strongly associated with environmental and psychosocial characteristics of women between 40 and 65 years of age.

Observed differences in learning ability of heart rate self-regulation as a function of hypnotic susceptibility

NASA Technical Reports Server (NTRS)

Cowings, P. S.

1977-01-01

Three groups of eight male and female subjects (aged 20-27 yr) categorized by low and high hypnotic susceptibility were taught to control their heart rates by means of an appropriate autogenic therapy/biofeedback technique. The experimental groups were trained by autogenic therapy and biofeedback, while the control group received only biofeedback. Significant differences are observed in all psychological test scores between subjects of high and low hypnotic susceptibility. The results confirm that (1) there are qualitative and quantitative differences between the performance of individuals with high and low hypnotic susceptibility; (2) interindividual-variability tests yield data relevant to individual performance in visceral learning tasks; (3) the combined autogenic therapy/biofeedback/verbal feedback technique is suitable for conditioning large stable autonomic responses in humans; and (4) this kind of conditioning is effective in eliminating or alleviating physiological reactions to some environmental stressors.

Hungarian norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.

PubMed

Költő, András; Gősi-Greguss, Anna C; Varga, Katalin; Bányai, Éva I

2015-01-01

Hungarian norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) are presented. The Hungarian translation of the HGSHS:A was administered under standard conditions to 434 participants (190 males, 244 females) of several professions. In addition to the traditional self-scoring, hypnotic behavior was also recorded by trained observers. Female participants proved to be more hypnotizable than males and so were psychology students and professionals as compared to nonpsychologists. Hypnotizability varied across different group sizes. The normative data-including means, standard deviations, and indicators of reliability-are comparable with previously published results. The authors conclude that measuring observer-scores increases the ecological validity of the scale. The Hungarian version of the HGSHS:A seems to be a reliable and valid measure of hypnotizability.

NEUROPEPTIDE MODULATION OF CHEMICALLY INDUCED SKIN IRRITATION

EPA Science Inventory

This study was designed to demonstrate that the early symptoms of chemically-induced skin irritation are neurally mediated. everal approaches were used to affect nerve transmission in adult Balb/c female mice. hese included general anesthesia (i.e., sodium pentobarbital), systemi...

[Prevalence of the use of hypnotics and sedatives among the working population and associated work-related stress factors].

PubMed

Colell, Esther; Sánchez-Niubò, Albert; Domingo-Salvany, Antònia; Delclós, Jordi; Benavides, Fernando G

2014-01-01

To explore the prevalence of the use of hypnotics and sedatives in a sample of the Spanish working population and to examine its association with certain work-related stress factors. Using data from the 2007 Spanish Household Survey on Alcohol and Drugs (Encuesta Domiciliaria sobre Alcohol y Drogas en España [EDADES]), we analyzed the distribution of the use of hypnotics and sedatives in the previous month in the working population aged 16 to 64 years old (n=13,005). Associations with exposure to certain work-related stress factors (noxious working environment, precariousness, workload, and social support) were examined using logistic regression modelling. The prevalence of the use of hypnotics and sedatives among women in the previous month doubled that of men (6.5% and 3.3%, respectively), while use among the oldest age group was twice that of the youngest group in both sexes (10.2% in women and 5.5% in men older than 45 years), and was four times higher among those reporting poor health (18.9% in women and 11% in men). Concerning work-related stress, exposure to moderate (OR: 1.96; 95%CI: 1.31-2.92) and high (OR: 1.95; 95%CI: 1.14-3.34) levels of precariousness in men and moderate levels in women (OR: 1.43; 95%CI: 1.03-1.99) was associated with the use of hypnotics and sedatives. The prevalence of the use of hypnotics and sedatives was high in women and in workers older than 45 years. Further research is needed on the relationship between the use of hypnotics and sedatives and workers' health, and on the role that work-related stress factors play in this association. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Hypnotic illusions and clinical delusions: a hypnotic paradigm for investigating delusions of misidentification.

PubMed

Cox, Rochelle E; Barnier, Amanda J

2009-01-01

In 2 experiments, the authors created a hypnotic analogue of delusions of misidentification and explored their impact on autobiographical memory. In Experiment 1, to establish the paradigm, high and low hypnotizable participants were given a suggestion to become someone similar or dissimilar to themselves. In Experiment 2, to further test the paradigm and to examine autobiographical remembering, highs were given a suggestion to become a same-sex sibling, administered 2 challenges to the temporary delusion, and asked to generate autobiographical memories. For high hypnotizable participants, the suggested delusions of misidentification were compelling and resistant to challenge. During these temporary delusions, participants generated specific autobiographical memories that reflected previously experienced events viewed from the perspective of the suggested identity. These findings highlight the instrumental value of hypnosis to the investigation and understanding of delusions and autobiographical memory.

Effect of hypnotic suggestion on knee extensor neuromuscular properties in resting and fatigued states

PubMed Central

Antonini Philippe, Roberta; Guglielmo, Luiz Guilherme A.

2018-01-01

Purpose The aim of this study was to investigate whether hypnotic suggestions can alter knee extensor neuromuscular function at rest and during exercise. Methods Thirteen healthy volunteers (8 men and 5 women, 27 ± 3 years old) took part in this counterbalanced, crossover study including two experimental (hypnosis and control) sessions. Knee extensor neuromuscular function was tested before and after hypnosis suggestion by using a combination of voluntary contraction, transcutaneous femoral nerve electrical stimulation and transcranial magnetic stimulation (TMS). A fatiguing exercise (sustained submaximal contraction at 20% maximal voluntary contraction (MVC) force) was also performed to evaluate the potential influence of hypnosis on the extent and origin of neuromuscular adjustments. Results Hypnosis did not (p>0.05) alter MVC force or knee extensor neural properties. Corticospinal excitability, assessed with the amplitude of knee extensor motor evoked potentials, was also unchanged (p>0.05), as was the level of intracortical inhibition assessed with paired pulse TMS (short-interval intracortical inhibition, SICI). Time to task failure (~300 s) was not different (p>0.05) between the two sessions; accordingly, hypnosis did not influence neuromuscular adjustments measured during exercise and at task failure (p>0.05). Conclusion Hypnotic suggestions did not alter neuromuscular properties of the knee extensor muscles under resting condition or during/after exercise, suggesting that hypnosis-induced improvement in exercise performance and enhanced corticospinal excitability might be limited to highly susceptible participants. PMID:29684047

An Intersubjective View of Empathy and Hypnotic Trance: Response to Wickramasekera II.

PubMed

Henning, Janna A

2016-01-01

In response to Wickramasekera II's description of his empathic involvement theory of hypnosis in "Mysteries of hypnosis and the self are revealed by the psychology and neuroscience of empathy" (Wickramasekera II, 2015), Henning offers further reflections on what empathy might be and what it allows therapists to do, particularly in conditions of hypnotic trance. She defines her intersubjective view of hypnotic trance as an experience in which client and therapist mutually engage in a shared state of consciousness, and a mutual bidirectional or multidirectional exchange of verbal and nonverbal, as well as conscious and unconscious, material occurs, and which may include shared taking on of roles and expectations in each party, as suggested by the other, particularly when both client and therapist are highly hypnotizable. Research on the concept of "mutual hypnosis," or co-trance, is reviewed, and barriers to scholarly discussions about intersubjectivity in therapy relationships are described. Concepts from other disciplines and traditions, including quantum physics, transpersonal psychology, contemplative Christianity, and shamanistic practices and trance in other cultures are then offered to clarify the processes of intersubjectivity, and perspectives about empathy and hypnotic co-trance are offered from the context of the author's own clinical work as a trauma therapist. Finally, suggestions are provided for future research approaches and methods to further explore and understand these phenomena.

A preconscious neural mechanism of hypnotically altered colors: a double case study.

PubMed

Koivisto, Mika; Kirjanen, Svetlana; Revonsuo, Antti; Kallio, Sakari

2013-01-01

Hypnotic suggestions may change the perceived color of objects. Given that chromatic stimulus information is processed rapidly and automatically by the visual system, how can hypnotic suggestions affect perceived colors in a seemingly immediate fashion? We studied the mechanisms of such color alterations by measuring electroencephalography in two highly suggestible participants as they perceived briefly presented visual shapes under posthypnotic color alternation suggestions such as "all the squares are blue". One participant consistently reported seeing the suggested colors. Her reports correlated with enhanced evoked upper beta-band activity (22 Hz) 70-120 ms after stimulus in response to the shapes mentioned in the suggestion. This effect was not observed in a control condition where the participants merely tried to simulate the effects of the suggestion on behavior. The second participant neither reported color alterations nor showed the evoked beta activity, although her subjective experience and event-related potentials were changed by the suggestions. The results indicate a preconscious mechanism that first compares early visual input with a memory representation of the suggestion and consequently triggers the color alteration process in response to the objects specified by the suggestion. Conscious color experience is not purely the result of bottom-up processing but it can be modulated, at least in some individuals, by top-down factors such as hypnotic suggestions.

Dispositional mindfulness, anticipation and abstinence symptoms related to hypnotic dependence among insomniac women who seek treatment: A cross-sectional study

PubMed Central

Demarzo, Marcelo; Curado, Daniela Fernández; Hachul, Helena

2018-01-01

Introduction Dispositional mindfulness can be described as the mental ability to pay attention to the present moment, non-judgmentally. There is evidence of inverse relation between dispositional mindfulness and insomnia and substance use, but as of yet, no studies evaluating the specific association between dispositional mindfulness and the components of hypnotic use disorder. Objective To evaluate the association between dispositional mindfulness and the components of dependence among female chronic hypnotic users. Design and method Seventy-six women, chronic users of hypnotics, who resorted to Mindfulness-Based Relapse Prevention for the cessation of hypnotic use were included in the study. The Five Facet Mindfulness Questionnaire (FFMQ) evaluated the levels and facets of mindfulness, and the subscales of the Benzodiazepine Dependence Questionnaire (BENDEP) assessed dependence on hypnotics. We also evaluated sociodemographic variables and symptoms of insomnia and anxiety. The associations between the FFMQ facets and the BENDEP subscales were evaluated with binomial logistic regression, adjusted for income, schooling, anxiety, and insomnia. Results We observed associations between facets of the FFMQ and specific aspects of hypnotic dependence. The facet “observing” was inversely associated with the “concern about lack of availability of the hypnotic” [aOR = 0.87 95% CI (0.79–0.97)], and the facet “non-reacting to inner experience” with “noncompliance with the prescription recommendations” [aOR = 0.86 95% CI (0.75–0.99)]. The total score of the FFMQ was inversely associated to those two dependence subscales [aOR = 0.94 95% CI (0.89–0.99)]. “Observing” and “non-reactivity to inner experience” were also inversely associated with the “impairments related to the withdrawal symptoms” [aOR = 0.84 95% CI (0.73–0.97)] and [aOR = 0.78 95% CI (0.63–0.96)], respectively. The FFMQ was not associated with “awareness of problematic

The Effect of Two Benzodiazepine Receptor Agonist Hypnotics on Sleep-Dependent Memory Consolidation

PubMed Central

Hall-Porter, Janine M.; Schweitzer, Paula K.; Eisenstein, Rhody D.; Ahmed, Hasan Ali H.; Walsh, James K.

2014-01-01

Introduction: Numerous studies have demonstrated that sleep promotes memory consolidation, but there is little research on the effect of hypnotics on sleep-dependent memory consolidation. We compared bedtime administration of zolpidem-ER 12.5 mg (6- to 8-h duration of action), middle-of-the-night administration of zaleplon 10 mg (3- to 4-h duration of action), and placebo to examine the effect of different durations of hypnotic drug exposure on memory consolidation during sleep. Methods: Twenty-two participants with no sleep complaints underwent 3 conditions in a counterbalanced crossover study: (1) zolpidem-ER 12.5 mg (bedtime dosing), (2) zaleplon 10 mg (middle-of-the-night dosing), and (3) placebo. Memory testing was conducted before and after an 8-h sleep period, using a word pair association task (WPT; declarative memory) and a finger-tapping task (FTT; procedural memory). Results: ANOVA revealed a significant condition effect for the WPT (p = 0.025) and a trend for the FTT (p = 0.067), which was significant when sex was added to the model (p = 0.014). Improvement in memory performance following sleep was lower with bedtime dosing of zolpidem-ER compared to placebo and middle-of-the-night dosing of zaleplon. There were no differences between placebo and zaleplon. Conclusions: The results suggest that in some circumstances hypnotics may have the potential to reduce the degree of sleep-dependent memory consolidation and that drug-free sleep early in the night may ameliorate this effect. Citation: Hall-Porter JM; Schweitzer PK; Eisenstein RD; Ahmed HAH; Walsh JK. The effect of two benzodiazepine receptor agonist hypnotics on sleep-dependent memory consolidation. J Clin Sleep Med 2014;10(1):27-34. PMID:24426817

ANXIETY REDUCTION AMONG BREAST-CANCER SURVIVORS RECEIVING HYPNOTIC RELAXATION THERAPY FOR HOT FLASHES

PubMed Central

Johnson, Alisa J.; Marcus, Joel; Hickman, Kimberly; Barton, Debra; Elkins, Gary

2017-01-01

Anxiety is common among breast-cancer survivors. This analysis examined the effect of a hypnotic relaxation therapy, developed to reduce hot flashes, on anxiety levels of female breast-cancer survivors. Anxiety was assessed using a numeric analog scale and the Hospital Anxiety and Depression Scale-Anxiety subscale. Significant reductions in anxiety were found from pre- to postintervention for each weekly session and were predictive of overall reductions in anxiety from baseline to after the last intervention. In this analysis, hypnotizability did not significantly predict for anxiety reductions measured before and after each session or from baseline to exit. These data provide initial support for the use of hypnotic relaxation therapy to reduce anxiety among breast-cancer survivors. PMID:27585723

Anxiety Reduction Among Breast-Cancer Survivors Receiving Hypnotic Relaxation Therapy for Hot Flashes.

PubMed

Johnson, Alisa J; Marcus, Joel; Hickman, Kimberly; Barton, Debra; Elkins, Gary

2016-01-01

Anxiety is common among breast-cancer survivors. This analysis examined the effect of a hypnotic relaxation therapy, developed to reduce hot flashes, on anxiety levels of female breast-cancer survivors. Anxiety was assessed using a numeric analog scale and the Hospital Anxiety and Depression Scale-Anxiety subscale. Significant reductions in anxiety were found from pre- to postintervention for each weekly session and were predictive of overall reductions in anxiety from baseline to after the last intervention. In this analysis, hypnotizability did not significantly predict for anxiety reductions measured before and after each session or from baseline to exit. These data provide initial support for the use of hypnotic relaxation therapy to reduce anxiety among breast-cancer survivors.

Continuing Versus New Prescriptions for Sedative-Hypnotic Medications: United States, 2005–2012

PubMed Central

Spira, Adam P.; Depp, Colin A.; Mojtabai, Ramin

2016-01-01

Objectives. To assess trends in continuing and new prescriptions for sedative-hypnotic medications, including benzodiazepines (BZDs) and non-BZD receptor agonists (nBZRAs). Methods. Data came from the National Ambulatory Medical Care Survey and comprised 287 288 randomly sampled patient visits. Physicians reported medications prescribed and whether they were “continuing” or “new” prescriptions. We assessed trends in continuing BZD, new BZD, continuing nBZRA, and new nBZRA prescriptions from 2005 to 2012. Results. Proportions of visits with continuing prescriptions increased from 3.4% in 2005 to 4.7% in 2012 (P < .01) for BZDs, and from 1.0% to 1.7% (P < .01) for nBZRAs. We noted no changes in new prescriptions. We observed the same patterns across patient age and physician specialties, except psychiatry. Despite no growth over time, the prevalence of visits involving continuing and new BZD and nBZRA prescriptions was much higher in psychiatry than in primary care and other specialties. Conclusions. Increased sedative-hypnotic prescribing in recent years may be attributable to long-term growth in continuing prescriptions, rather than new prescriptions. Public Health Implications. Findings call for renewed efforts to limit continuing prescribing of sedative-hypnotics to reduce their use in the population. PMID:27631754

Norms of German adolescents for the Harvard Group Scale of Hypnotic Susceptibility, Form A.

PubMed

Peter, Burkhard; Geiger, Emilia; Prade, Tanja; Vogel, Sarah; Piesbergen, Christoph

2015-01-01

The Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) has not been explicitly tested on an adolescent population. In this study, the German version of the HGSHS:A was administered to 99 German adolescents aged 15 to 19. In contrast to other studies, the gender distribution was relatively balanced: 57% female and 43% male. Results were comparable to 14 earlier studies with regard to distribution, mean, and standard deviation. Some peculiarities in contrast to the 14 previous studies are pointed out. It is concluded that the HGSHS:A can be used as a valid and reliable instrument to measure hypnotic suggestibility in adolescent samples.

Sedative and Hypnotic Activities of the Methanolic and Aqueous Extracts of Lavandula officinalis from Morocco

PubMed Central

Alnamer, Rachad; Alaoui, Katim; Bouidida, El Houcine; Benjouad, Abdelaziz; Cherrah, Yahia

2012-01-01

We evaluate the sedative and hypnotic activities of the methanolic and aqueous extract of Lavandula officinalis L. on central nervous system (CNS). In this study, the effect of the methanolic and aqueous extracts of this plant was investigated in a battery of behavioural models in mice. Stems and flowers of Lavandula officinalis L. have several therapeutic applications in folk medicine in curing or managing a wide range of diseases, including insomnia. The methanolic extract produced significant sedative effect at the doses of 200, 400, and 600 mg/kg (by oral route), compared to reference substance diazepam (DZP), and an hypnotic effect at the doses of 800 and 1000 mg/kg while the treatment of mice with the aqueous extract at the doses of 200 and 400 mg/kg via oral pathway significantly reduced in both the reestablishment time and number of head dips during the traction and hole-board tests. In conclusion, these results suggest that the methanolic and aqueous extracts of Lavandula officinalis possess potent sedative and hypnotic activities, which supported its therapeutic use for insomnia. PMID:22162677

Flumazenil antagonizes the central effects of zolpidem, an imidazopyridine hypnotic.

PubMed

Patat, A; Naef, M M; van Gessel, E; Forster, A; Dubruc, C; Rosenzweig, P

1994-10-01

Zolpidem is a new imidazopyridine-hypnotic that selectively binds to the central omega 1-receptor subtype. A double-blind, randomized, three-way, crossover placebo-controlled study was carried out in nine healthy male volunteers to assess the possible antagonism of central nervous system--depressant effects of zolpidem by flumazenil. Subjects received zolpidem (0.21 mg/kg) or placebo, intravenously, followed 17 minutes later by flumazenil (0.04 mg/kg) or placebo. Vigilance and performance were assessed by a trained anesthetist with use of ciliary reflex, response to a verbal instruction, subjective sedation, a tracking task, and a free recall task. Zolpidem produced a clinically relevant hypnotic effect in five subjects and significantly impaired performance in all nine subjects up to 90 minutes after dosing. Flumazenil rapidly antagonized clinical sedation in the five subjects who were asleep and significantly reversed the performance decrement within 3 minutes, without any escape phenomenon. Flumazenil did not change zolpidem plasma concentrations, confirming the pharmacodynamic nature of the interaction. Flumazenil may thus be a safe and effective antidote in patients with zolpidem overdosage.

76 FR 19375 - Safety and Efficacy of Hypnotic Drugs; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Safety and Efficacy of Hypnotic Drugs; Public Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public meeting. The Food and Drug Administration (FDA) is announcing a public meeting to...

Insomnia and hypnotic medications are associated with suicidal ideation in a community population.

PubMed

Pigeon, Wilfred R; Woosley, Julie A; Lichstein, Kenneth L

2014-01-01

Suicidal ideation (SI), a significant predictor of suicide, is associated with sleep disturbance, which is seldom assessed using stringent diagnostic criteria and validated sleep instruments in community samples. Cross-sectional data, including sleep diaries and validated instruments, from 767 community adults were used to identify variables associated with SI and subsequently entered into a regression model to predict SI. Suicidal ideation was endorsed by 9.3% of the sample. This group differed from non-ideators on several variables, but only insomnia diagnosis, depression severity, and hypnotic medication use predicted SI. Findings confirm an association of insomnia with SI using stringent criteria and controlling for depression. If treating insomnia is a conceivable pathway to reduce SI, the apparent risk posed by hypnotics may limit treatment options.

Cognitive Skill and Traditional Trance Hypnotic Inductions: A Within-Subjects Comparison.

ERIC Educational Resources Information Center

Vickery, Anne R.; And Others

1985-01-01

Compared a traditional trance hypnotic induction and a cognitive skill induction using a within-subjects design with college students (N=40). The skill induction enhanced responses to suggestions and produced marginally significant increments in behavioral responses when preceded by the trance induction, but there were no significant differences…

Enhanced visual memory during hypnosis as mediated by hypnotic responsiveness and cognitive strategies.

PubMed

Crawford, H J; Allen, S N

1983-12-01

To investigate the hypothesis that hypnosis has an enhancing effect on imagery processing, as mediated by hypnotic responsiveness and cognitive strategies, four experiments compared performance of low and high, or low, medium, and high, hypnotically responsive subjects in waking and hypnosis conditions on a successive visual memory discrimination task that required detecting differences between successively presented picture pairs in which one member of the pair was slightly altered. Consistently, hypnotically responsive individuals showed enhanced performance during hypnosis, whereas nonresponsive ones did not. Hypnotic responsiveness correlated .52 (p less than .001) with enhanced performance during hypnosis, but it was uncorrelated with waking performance (Experiment 3). Reaction time was not affected by hypnosis, although high hypnotizables were faster than lows in their responses (Experiments 1 and 2). Subjects reported enhanced imagery vividness on the self-report Vividness of Visual Imagery Questionnaire during hypnosis. The differential effect between lows and highs was in the anticipated direction but not significant (Experiments 1 and 2). As anticipated, hypnosis had no significant effect on a discrimination task that required determining whether there were differences between pairs of simultaneously presented pictures. Two cognitive strategies that appeared to mediate visual memory performance were reported: (a) detail strategy, which involved the memorization and rehearsal of individual details for memory, and (b) holistic strategy, which involved looking at and remembering the whole picture with accompanying imagery. Both lows and highs reported similar predominantly detail-oriented strategies during waking; only highs shifted to a significantly more holistic strategy during hypnosis. These findings suggest that high hypnotizables have a greater capacity for cognitive flexibility (Batting, 1979) than do lows. Results are discussed in terms of several

High Prevalence of Inappropriate Benzodiazepine and Sedative Hypnotic Prescriptions among Hospitalized Older Adults.

PubMed

Pek, Elisabeth Anna; Remfry, Andrew; Pendrith, Ciara; Fan-Lun, Chris; Bhatia, R Sacha; Soong, Christine

2017-05-01

Benzodiazepines and sedative hypnotics are commonly used to treat insomnia and agitation in older adults despite significant risk. A clear understanding of the extent of the problem and its contributors is required to implement effective interventions. To determine the proportion of hospitalized older adults who are inappropriately prescribed benzodiazepines or sedative hypnotics, and to identify patient and prescriber factors associated with increased prescriptions. Single-center retrospective observational study. Urban academic medical center. Medical-surgical inpatients aged 65 or older who were newly prescribed a benzodiazepine or zopiclone. Our primary outcome was the proportion of patients who were prescribed a potentially inappropriate benzodiazepine or sedative hypnotic. Potentially inappropriate indications included new prescriptions for insomnia or agitation/anxiety. We used a multivariable random-intercept logistic regression model to identify patient- and prescriber-level variables that were associated with potentially inappropriate prescriptions. Of 1308 patients, 208 (15.9%) received a potentially inappropriate prescription. The majority of prescriptions, 254 (77.4%), were potentially inappropriate. Of these, most were prescribed for insomnia (222; 87.4%) and during overnight hours (159; 62.3%). Admission to a surgical or specialty service was associated with significantly increased odds of potentially inappropriate prescription compared to the general internal medicine service (odds ratio [OR], 6.61; 95% confidence interval [CI], 2.70-16.17). Prescription by an attending physician or fellow was associated with significantly fewer prescriptions compared to first-year trainees (OR, 0.28; 95% CI, 0.08-0.93). Nighttime prescriptions did not reach significance in initial bivariate analyses but were associated with increased odds of potentially inappropriate prescription in our regression model (OR, 4.48; 95% CI, 2.21-9.06). The majority of newly

Increased response time of primed associates following an "episodic" hypnotic amnesia suggestion: a case of unconscious volition.

PubMed

Smith, Caleb Henry; Oakley, David A; Morton, John

2013-12-01

Following a hypnotic amnesia suggestion, highly hypnotically suggestible subjects may experience amnesia for events. Is there a failure to retrieve the material concerned from autobiographical (episodic) memory, or is it retrieved but blocked from consciousness? Highly hypnotically suggestible subjects produced free-associates to a list of concrete nouns. They were then given an amnesia suggestion for that episode followed by another free association list, which included 15 critical words that had been previously presented. If episodic retrieval for the first trial had been blocked, the responses on the second trial should still have been at least as fast as for the first trial. With semantic priming, they should be faster. In fact, they were on average half a second slower. This suggests that the material had been retrieved but blocked from consciousness. A goal-oriented information processing framework is outlined to interpret these and related data. Copyright © 2013 Elsevier Inc. All rights reserved.

Effectiveness of a CBT Intervention for Persistent Insomnia and Hypnotic Dependency in an Outpatient Psychiatry Clinic.

PubMed

Taylor, Hannah Lund; Rybarczyk, Bruce D; Nay, William; Leszczyszyn, David

2015-07-01

To test cognitive-behavioral therapy for insomnia (CBT-I) in patients who not only receive psychiatric treatment in a outpatient psychiatry clinic but also continue to experience chronic insomnia despite receiving pharmacological treatment for sleep. CBT-I included an optional module for discontinuing hypnotic medications. Patients were randomized to 5 sessions of individual CBT-I (n = 13) or treatment as usual (n = 10). Sleep parameters were assessed using sleep diaries at pre- and posttreatment. Questionnaires measuring depression, anxiety, and health-related quality of life were also administered. CBT-I was associated with significant improvement in sleep, with 46% obtaining normal global sleep ratings after treatment. However, no changes in secondary outcomes (depression, anxiety, quality of life) were obtained and no patients elected to discontinue their hypnotic medications. Patients with complex, chronic psychiatric conditions can obtain sleep improvements with CBT-I beyond those obtained with pharmacotherapy alone; however, sleep interventions alone may not have the same effect on mental health outcomes in samples with more severe and chronic psychiatric symptoms and dependency on hypnotic medications. © 2015 Wiley Periodicals, Inc.

An unanticipated allergic reaction to a hypnotic suggestion for anesthesia: a brief communication and commentary.

PubMed

Guttman, Kenneth; Ball, Thomas S

2013-01-01

During a demonstration of hypnotically induced anesthesia and following a suggestion for a Novocain-like numbness, a totally unanticipated and dramatic swelling of 1 cheek appeared. The participant had forgotten to inform the psychologist that she had experienced the identical reaction to Novocain when she received an injection a few weeks earlier. The swelling was quickly removed by a countersuggestion based upon a simulated injection of the antidote previously administered by the dentist. This case report is relevant to current research and theorizing on the interaction of hypnosis with the immune system. The fact that it was retrospectively recognized as a single-case time-series B-A-B design significantly enhances its scientific value beyond that afforded by the traditional case report.

A Sleep Education and Hypnotics Reduction Program for Hospitalized Patients at a General Hospital

PubMed Central

Youn, Soyoung; Park, Boram; Lee, Suyeon; Kim, Changnam

2018-01-01

Objective We applied a program of sleep education and hypnotics reduction for inpatients (the i-sleep program). This study explored whether the i-sleep program is effective for reducing the prescription rate of sleeping pills to inpatients in a general hospital. Methods We estimated the proportion of inpatients prescribed hypnotics at admission to and discharge from the hospital, excluding pediatric care units, before (2014) and after (2015) the program. In addition, we estimated the proportion of inpatients prescribed sleeping pills among all inpatients on the first day of each month of 2014 and 2015. Results The proportion of inpatients prescribed hypnotics as discharge medication among inpatients who had been prescribed them at the time of admission decreased significantly, from 57.0% to 46.8%, after the i-sleep program (RR=0.82, 95% CI: 0.79–0.86). The proportion of inpatients newly prescribed sleeping pills after admission to the hospital did not significantly decrease (1.97% to 2.00%; RR=1.01, 95% CI: 0.96–1.07). The mean prescription rate of sleeping pills per day was 8.18% in 2014 and 7.78% in 2015. Conclusion The i-sleep program reduced the proportion of inpatients who continued to take sleeping pills from admission until discharge, although it did't reduce the prescription rate per day. PMID:29422929

Rosewood oil induces sedation and inhibits compound action potential in rodents.

PubMed

de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

2009-07-30

Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

Can grapheme-color synesthesia be induced by hypnosis?

PubMed Central

Anderson, Hazel P.; Seth, Anil K.; Dienes, Zoltan; Ward, Jamie

2014-01-01

Grapheme-color synesthesia is a perceptual experience where graphemes, letters or words evoke a specific color, which are experienced either as spatially coincident with the grapheme inducer (projector sub-type) or elsewhere, perhaps without a definite spatial location (associator sub-type). Here, we address the question of whether synesthesia can be rapidly produced using a hypnotic color suggestion to examine the possibility of “hypnotic synesthesia”, i.e., subjectively experienced color hallucinations similar to those experienced by projector synesthetes. We assess the efficacy of this intervention using an “embedded figures” test, in which participants are required to detect a shape (e.g., a square) composed of local graphemic elements. For grapheme-color synesthetes, better performance on the task has been linked to a higher proportion of graphemes perceived as colored. We found no performance benefits on this test when using a hypnotic suggestion, as compared to a no-suggestion control condition. The same result was found when participants were separated according to the degree to which they were susceptible to the suggestion (number of colored trials perceived). However, we found a relationship between accuracy and subjective reports of color in those participants who reported a large proportion of colored trials: trials in which the embedded figure was accurately recognized (relative to trials in which it was not) were associated with reports of more intense colors occupying a greater spatial extent. Collectively, this implies that hypnotic color was only perceived after shape detection rather than aiding in shape detection via color-based perceptual grouping. The results suggest that hypnotically induced colors are not directly comparable to synesthetic ones. PMID:24829555

Pregnancy and pentobarbital anaesthesia modify hepatic synthesis of acylglycerol glycerol and glycogen from gluconeogenic precursors during fasting in rats.

PubMed Central

Zorzano, A; Herrera, E

1988-01-01

1. Incorporation of gluconeogenic precursors into blood glucose and hepatic glycogen and acylglycerol glycerol was examined in 24 h-fasted virgin rats by using a flooding procedure for substrate administration. At 10 min after their intravenous injection, the conversion of alanine or glycerol into liver glycogen or acylglycerol glycerol was proportional to glucose synthesis. 2. In 24 h-fasted 21-day-pregnant rats, the incorporation of alanine and glycerol into hepatic acylglycerol glycerol was markedly enhanced compared with the control group. In addition, during fasting at late pregnancy, the proportion of substrates directed to acylglycerol glycerol as compared with the fraction incorporated into glucose was augmented. 3. In pentobarbital-treated fasted rats, the incorporation of both alanine and pyruvate into circulating glucose and into hepatic glycogen and acylglycerol glycerol was increased. Pentobarbital treatment increased the proportion of substrates incorporated into liver glycogen, compared with the fraction appearing in circulating glucose. These changes were concomitant with a marked accumulation of glycogen. 4. The data indicate that, during fasting, gluconeogenesis provides glucose as well as hepatic glycogen and acylglycerol glycerol, independently of whether the substrates enter gluconeogenesis at the level of pyruvate or dihydroxyacetone phosphate. PMID:3223926

Developing a Hypnotic Relaxation Intervention to Improve Body Image: A Feasibility Study.

PubMed

Cieslak, Alison; Elkins, Gary; Banerjee, Tanima; Marsack, Jessica; Hickman, Kimberly; Johnson, Alisa; Henry, Norah; Barton, Debra

2016-11-01

To determine the content, feasibility, and best outcome of a mind-body intervention involving self-directed hypnotic relaxation to target body image.
. A five-week, uncontrolled, unblinded feasibility intervention study.
. Behavioral therapy offices in Ann Arbor, Michigan, and Waco, Texas.
. 10 female breast cancer survivors and 1 breast and gynecologic cancer survivor. 
. Adult women with a history of breast and gynecologic cancer and no major psychiatric history were eligible. The intervention included four face-to-face sessions with a research therapist lasting 40-60 minutes, logged home practice, one telephone check-in call at week 5, and one intervention feedback telephone call to complete the study. Descriptive statistics and paired t-tests were used to test feasibility and content validity.
. Stress from body changes as measured by the Impact of Treatment Scale, sexual function as measured by the Female Sexual Function Index, and sexual self-image as measured by the Sexual Self-Schema Scale for women were the variables of interest.
. The intervention content was confirmed. Changes in scores from the baseline to week 5 suggested that stress from body changes decreased and sexual self-schema and function improved during the intervention. Nine of the 11 women were satisfied with the intervention, and all 11 indicated that their body image improved. 
. Hypnotic relaxation therapy shows promise for improving body image and, in doing so, improving sexual health in this population. Additional testing of this intervention is warranted.
. Hypnotic relaxation therapy is feasible to improve body image and sexual health in women diagnosed with cancer and may be an important intervention that could be offered by nurses and other behavioral therapists.

[Studies of time-course changes in human body balance after ingestion of long-acting hypnotics].

PubMed

Nakamura, Masahiro; Ishii, Masanori; Niwa, Yoji; Yamazaki, Momoko; Ito, Hiroshi

2004-02-01

Falling accidents are a serious nocosomial problem, with balance disorders after the ingestion of hypnotics said to be a cause. Based on the results of animal studies, it was postulated that this problem involves the muscle relaxation that is a pharmacological effect of benzodiazepines (BZP). No reports have, to our knowledge, been made of time-course changes in human body balance after ingestion of hypnotics. Accordingly, we used quazepam (Doral), a long-acting hypnotic considered to show comparatively weak muscle relaxation, to study static balance after drug ingestion in human volunteers. Briefly, informed consent was obtained from 8 healthy adults, then a gait analytic system (Gangas) was used to test static balance after drug ingestion (Mann and Romberg tests). We also measured circulating drug concentration over time. Our results showed that balance disorders occurred after quazepam ingestion with an unstable posture particularly striking. Given the function of quazepam receptors, it is difficult to surmise that balance disorders after drug ingestion were due to the drug's muscle relaxation. We surmised that inhibition from the central nervous system in connection with nerves awakening was involved. We found a strong correlation between the manifestation of balance disorders after drug ingestion and circulating drug concentration.

Temporal changes in postural sway caused by ultrashort-acting hypnotics: triazolam and zolpidem.

PubMed

Nakamura, M; Ishii, M; Niwa, Y; Yamazaki, M; Ito, H

2005-01-01

Two ultrashort-acting hypnotics, triazolam 0.25 mg and zolpidem 10 mg, were studied for their effects on equilibrium function in humans. Eight healthy male subjects participated in a double-blind, placebo-controlled study after informed consent. They subjected to static equilibrium tests, oculomotor tests and an assay of drug concentrations in the blood. Zolpidem was statistically significant in postural sway in tandem stance test, as defined by parametric values of tracing sum length and polygonal area of foot pressure center measured by a gait analysis system. In the tandem stance test, triazolam was statistically significant in postural sway only as defined by the polygonal area. However, in the Romberg test, the only statistically significant difference in zolpidem use was observed in polygonal area values. Blood concentrations of triazolam and zolpidem were found to closely correlate with the extent of postural sway in both tandem stance and Romberg tests. In this study, zolpidem with minimal muscle-relaxant effect incurred imbalance more extensively than triazolam, which is known for its effect of muscle relaxation. In addition, gaze deviation nystagmus was observed only in zolpidem use in 5 of 8 subjects (62.5%). From these results, it is suggested that in the use of hypnotics, sway derives from the suppression of the central nervous system relevant to awakening rather than from muscle relaxation. The prior reference to blood concentrations of hypnotics should help improve safety care in minimizing loss of balance control and possible fall. Copyright 2005 S. Karger AG, Basel.

[Hospital Emergencies Associated with the Consumption of Hypnotics and Sedatives, 2009-2013,Castilla y León, Spain].

PubMed

Rubio González, Verónica; Redondo Martín, Susana; Ruíz López Del Prado, Gema; Muñoz Moreno, Mª Fe; Velázquez Miranda, Alexander

2016-10-24

Household Survey on Alcohol and Other Drugs shows the progressive increase in the consumption of hypnotics, alone or in combination with other substances. The aim of the research was to obtain information about the consumption of hypnotics and sedatives in population of Castilla y León treated in emergency medical services of four monitored hospitals between 2009-2013, describing clinical and epidemiological characteristics of the emergencies and what drugs were consumed, to provide information for future interventions. A descriptive cross-sectional study was done by analyzing 3,089 emergencies related to consumption of hypnotics and sedatives, obtained from Emergency Indicator related to the use of psychoactive substances of the National Observatory on Drugs. There were used χ2 test for comparing proportions and t Student test for means. The total number of emergencies was 3,089, ranging in years of study. In 1,814 cases they were consumed only hypnosedatives; 64.7% women and average age of 41 years. The most frequent diagnosis was overdose/attempted suicide with benzodiazepines (29.3%), being lorazepam the most consumed. In 23.3% of cases it was consumed more than one hypnosedative and 9% was associated with psychiatric disorders. The number of emergencies related to the consumption of at least one hypnosedative in the monitored hospitals in the period studied presented high levels especially in middle-aged women with no psychiatric disorder to justify their use. Benzodiazepines were the most consumed hypnotics, cause of overdose/attempted suicide episodes.

[Hypnotic communication and hypnosis in clinical practice].

PubMed

Wehrli, Hans

2014-07-02

In addition to usual medical care it is often critical to consider the patient's inner world in order to sensitively differentiate between harmful and helpful suggestive elements. The respective abilities in terms of hypnotic communication can be easily learned. Confident, empathic attention and a calm, understanding and figurative language narrowing the focus on positive emotions and positive change, which have been shown to improve the patient's chances of healing, are of particular importance. Proper clinical hypnosis goes one step further: it makes explicit use of suggestions, trance, and trance phenomena. The major clinical indications for hypnosis include psychosomatic disorders, anxiety disorders, obsessive-compulsive disorders, depression, and pain syndromes. Hypnosis can also be employed as an adjunct for surgical therapy.

Cognitive-behavioral therapy and hypnotic relaxation to treat sleep problems in an adolescent with diabetes.

PubMed

Perfect, Michelle M; Elkins, Gary R

2010-11-01

Inadequate sleep among adolescents frequently contributes to obesity and reduced academic performance, along with symptoms of anxiety, depression, fatigue, and attention deficits. The etiological bases of sleep quality has been associated with both stress and sleep habits. These problems tend to be especially important for adolescents with diabetes as the effects of poor sleep complicate health outcomes. This case example concerns a 14-year-old adolescent girl with a history of type I diabetes and stress-related sleep difficulties. Treatment included cognitive-behavioral methods and hypnotic relaxation therapy. Results of this case example and other controlled research suggest that hypnotic relaxation therapy is well accepted, results in good compliance, and serves as a useful adjunctive to cognitive-behavioral intervention for sleep problems. © 2010 Wiley Periodicals, Inc.

Sleep duration and ischemic heart disease and all-cause mortality: prospective cohort study on effects of tranquilizers/hypnotics and perceived stress.

PubMed

Garde, Anne Helene; Hansen, Åse Marie; Holtermann, Andreas; Gyntelberg, Finn; Suadicani, Poul

2013-11-01

This prospective study aimed to examine if sleep duration is a risk indicator for ischemic heart disease (IHD) and all-cause mortality, and how perceived stress during work and leisure time and use of tranquilizers/hypnotics modifies the association. A 30-year follow-up study was carried out in the Copenhagen Male Study comprising 5249 men (40-59 years old). Confounders included lifestyle factors (smoking, alcohol, and leisure-time physical activity), clinical and health-related factors (body mass index, blood pressure, diabetes, hypertension, and physical fitness) and social class. Men with a history of cardiovascular disease at baseline were excluded. During follow-up, 587 men (11.9%) died from IHD and 2663 (53.9%) due to all-cause mortality. There were 276 short (<6 hours), 3837 medium (6-7 hours), and 828 long (≥8 hours) sleepers. Men who slept <6 hours had an increased risk of IHD mortality but not all-cause mortality, when referencing medium sleepers. Perceived psychological pressure during work and leisure was not a significant effect modifier for the association between sleep duration and IHD mortality. In contrast, among men using tranquilizers/hypnotics (rarely or regularly), short sleepers had a two-to-three fold increased risk of IHD mortality compared to medium sleepers. Among those never using tranquilizers/hypnotics, no association was observed between sleep duration and IHD mortality. Short sleep duration is a risk factor for IHD mortality among middle-aged and elderly men, particularly those using tranquilizers/hypnotics on a regular or even a rare basis, but not among men not using tranquilizers/hypnotics.

The effect of posthypnotic suggestion, hypnotic suggestibility, and goal intentions on adherence to medical instructions.

PubMed

Carvalho, Claudia; Mazzoni, Giuliana; Kirsch, Irving; Meo, Maria; Santandrea, Maura

2008-04-01

The effects of implementation intentions and posthypnotic suggestion were investigated in 2 studies. In Experiment 1, participants with high levels of hypnotic suggestibility were instructed to take placebo pills as part of an investigation of how to best enhance compliance with medical instruction. In Experiment 2, participants with high, medium, and low levels of hypnotic suggestibility were asked to run in place, take their pulse rate before, and send an e-mail report to the experimenter each day. Experiment 1 revealed enhanced adherence as a function of both implementation intentions and posthypnotic suggestion. Experiment 2 failed to find any significant main effects but found a significant interaction between suggestibility and the effects of posthypnotic suggestion. Posthypnotic suggestion enhanced adherence among high suggestible participants but lowered it among low suggestibles.

Spectral entropy as a measure of hypnosis and hypnotic drug effect of total intravenous anesthesia in children during slow induction and maintenance.

PubMed

Klockars, Jaakko G M; Hiller, Arja; Münte, Sinikka; van Gils, Mark J; Taivainen, Tomi

2012-02-01

We evaluated whether spectral entropy (SpE) can measure the depth of hypnosis and the hypnotic drug effect in children during total intravenous anesthesia. Sixty healthy children, aged 3-16 yr, were studied. Anesthesia was induced with an increasing target controlled infusion of propofol, and maintained by a stable remifentanil infusion and variable concentrations of target controlled infusion propofol. Depth of hypnosis was assessed according to the University of Michigan Sedation Scale (UMSS). Estimated plasma (C(p)) and pseudo effect site (C(eff)) propofol concentrations reflected the hypnotic drug effect. Patients were stratified to three age groups. The correlations between SpE versus UMSS, C(p), and C(eff) were analyzed by Prediction Probability (P(k)). The pharmacodynamic relationship between SpE and C(p), and the differences of SpE values between the age groups at the corresponding UMSS levels, were studied. Respective mean P(k) values for the youngest, middle, and oldest age groups were: 1) during induction: SpE versus UMSS 0.87, 0.87, and 0.93; SpE versus C(p) 0.92, 0.95, and 0.97; and SpE versus C(eff) 0.88, 0.94, and 0.95; 2) during maintenance: SpE versus C(eff) 0.86, 0.75, and 0.81. The pharmacodynamic analysis determined an association between SpE and C(p) that followed the E(max) model closely. There were significant differences in SpE values between age groups at corresponding UMSS sedation levels. SpE measures the level of hypnosis and hypnotic drug effect in children during total intravenous anesthesia. There is an age dependency associated with SpE. Anesthesia should not be steered solely on the basis of SpE.

Hypnotic hypersensitivity to volatile anesthetics and dexmedetomidine in dopamine β-hydroxylase knockout mice.

PubMed

Hu, Frances Y; Hanna, George M; Han, Wei; Mardini, Feras; Thomas, Steven A; Wyner, Abraham J; Kelz, Max B

2012-11-01

Multiple lines of evidence suggest that the adrenergic system can modulate sensitivity to anesthetic-induced immobility and anesthetic-induced hypnosis as well. However, several considerations prevent the conclusion that the endogenous adrenergic ligands norepinephrine and epinephrine alter anesthetic sensitivity. Using dopamine β-hydroxylase knockout (Dbh) mice genetically engineered to lack the adrenergic ligands and their siblings with normal adrenergic levels, we test the contribution of the adrenergic ligands upon volatile anesthetic induction and emergence. Moreover, we investigate the effects of intravenous dexmedetomidine in adrenergic-deficient mice and their siblings using both righting reflex and processed electroencephalographic measures of anesthetic hypnosis. We demonstrate that the loss of norepinephrine and epinephrine and not other neuromodulators co-packaged in adrenergic neurons is sufficient to cause hypersensitivity to induction of volatile anesthesia. However, the most profound effect of adrenergic deficiency is retarding emergence from anesthesia, which takes two to three times as long in Dbh mice for sevoflurane, isoflurane, and halothane. Having shown that Dbh mice are hypersensitive to volatile anesthetics, we further demonstrate that their hypnotic hypersensitivity persists at multiple doses of dexmedetomidine. Dbh mice exhibit up to 67% shorter latencies to loss of righting reflex and up to 545% longer durations of dexmedetomidine-induced general anesthesia. Central rescue of adrenergic signaling restores control-like dexmedetomidine sensitivity. A novel continuous electroencephalographic analysis illustrates that the longer duration of dexmedetomidine-induced hypnosis is not due to a motor confound, but occurs because of impaired anesthetic emergence. Adrenergic signaling is essential for normal emergence from general anesthesia. Dexmedetomidine-induced general anesthesia does not depend on inhibition of adrenergic neurotransmission.

Hypnotic Hypersensitivity to Volatile Anesthetics and Dexmedetomidine in Dopamine β-Hydroxylase Knockout Mice

PubMed Central

Hu, Frances Y.; Hanna, George M.; Han, Wei; Mardini, Feras; Thomas, Steven A.; Wyner, Abraham J.; Kelz, Max B.

2012-01-01

BACKGROUND Multiple lines of evidence suggest that the adrenergic system can modulate sensitivity to anesthetic-induced immobility and anesthetic-induced hypnosis as well. However, several considerations prevent the conclusion that the endogenous adrenergic ligands norepinephrine and epinephrine alter anesthetic sensitivity. METHODS Using dopamine β-hydroxylase (Dbh−/−) mice genetically engineered to lack the adrenergic ligands and their siblings with normal adrenergic levels, we test the contribution of the adrenergic ligands upon volatile anesthetic induction and emergence. Moreover, we investigate the effects of intravenous dexmedetomidine in adrenergic-deficient mice and their siblings using both righting reflex and processed electroencephalographic measures of anesthetic hypnosis. RESULTS We demonstrate that the loss of norepinephrine and epinephrine and not other neuromodulators copackaged in adrenergic neurons is sufficient to cause hypersensitivity to induction of volatile anesthesia. However, the most profound effect of adrenergic deficiency is retarding emergence from anesthesia, which takes two to three times as long in Dbh−/− mice for sevoflurane, isoflurane, and halothane. Having shown that Dbh−/− mice are hypersensitive to volatile anesthetics, we further demonstrate that their hypnotic hypersensitivity persists at multiple doses of dexmedetomidine. Dbh−/− mice exhibit up to 67% shorter latencies to loss of righting reflex and up to 545% longer durations of dexmedetomidine-induced general anesthesia. Central rescue of adrenergic signaling restores control-like dexmedetomidine sensitivity. A novel continuous electroencephalographic analysis illustrates that the longer duration of dexmedetomidine-induced hypnosis is not due to a motor confound, but occurs because of impaired anesthetic emergence. CONCLUSIONS Adrenergic signaling is essential for normal emergence from general anesthesia. Dexmedetomidine-induced general anesthesia does

The Gastrointestinal Irritation of Polygala Saponins and Its Potential Mechanism In Vitro and In Vivo

PubMed Central

Wen, Li; Xia, Nan; Tang, PeiPei; Hong, Yi; Wang, ZiZhen; Liu, YaJie; Liu, YanJu; Liu, JianJun; Li, XiangQiong

2015-01-01

Processing alters the pharmacological activity and reduces the gastrointestinal toxicity of the polygalae. To investigate the effect of processing, different glycosyl substituent products were tested. Hypnotic and subhypnotic doses of pentobarbital-induced sleep tests on mice were used to evaluate the sedative activity of polygala saponins with different glycosyl substituents; isolated gut motility experiment was employed to study excitatory effects of different polygala saponins; the gastrointestinal irritation effects of different polygala saponins were compared by measuring the levels of gastric PGE2 and intestinal TNF-α on mice. When compared with control, Onjisaponin B (OJB) and tenuifolin (TEN), but not senegenin (SNG), significantly increased the number of sleeping mice and prolonged the sleeping time (P < 0.05); 80, 40, and 20 mg/L of OJB and 80 mg/L of TEN, but not SNG, obviously changed the amplitude and frequency of isolated jejunum (P < 0.05); all the three compounds significantly decreased the level of gastric PGE2 but had no obvious influences on the reduction of intestinal TNF-α level. For sedative and hypnotic effects, OJB > TEN > SNG; for the protection form gastrointestinal irritation and damages, OJB > TEN > SNG. Therefore, in processing Polygala, glycosyl breaking may be related to the decline of pharmacological activity and gastrointestinal toxicity of polygala saponins. PMID:25705699

Hypnotic approach during dental treatment: analysis of descriptive data of a case series.

PubMed

Ferdeghini, R; Lauritano, D; Tagliabue, A; Tettamanti, L

2018-01-01

Anxiety and worry are important components that affect the patient’s behaviour during dental sessions and influence the effectiveness of dental treatment. Psychological approach and hypnotic approach (HA) have in recent years assumed increasing prominence as effective treatment regimes. Dentists have used a number of methods in the management of dental phobic disorders through HA. However the efficacy of HA in controlling anxiety and worry is controversial. The aim of the present study is to describe the response of patient to HA during dental treatment. The study of the population consisted of 42 patients, these being 50% random sample of consecutive patients presenting to a private practise over an 8-year period. In 38 patients HA was induced. 4 patients were not susceptible to HA. There were 20 women (52.6%) and 18 men (47.3%) with a mean age of 47.2 years (range 30-69 years). At the end of dental sessions with HA all the patients were asked to answer the following questions: 1) Have you been hypnotized in the past? 2) Were you aware of dental applications of HA? 3) How do you evaluate the use of this technique in the field of dental care? 4) Do you think that you can use this procedure in the future too? The answers were as follows: question 1: 34 patients answered yes, 4 no; question 2: 34 answered yes, 4 no; question 3: the choice was between “very useful”, “useful”, “Indifferent”, “to avoid”. Twenty-nine patients indicated “very useful”, and 9 “useful”; question 4: the choice was between yes and no. All patients answered yes. This study adds further support to a growing body of evidence relating HA to a better compliance to dental treatment. The dental situation in particular lends itself to carefully controlled investigation providing further evidence to support a robust theory.

Chaotic patterns of autonomic activity during hypnotic recall.

PubMed

Bob, Petr; Siroka, Ivana; Susta, Marek

2009-01-01

Chaotic neural dynamics likely emerge in cognitive processes and may present time periods that are extremely sensitive to influences affecting the neural system. Recent findings suggest that this sensitivity may increase during retrieval of stressful emotional experiences reflecting underlying mechanism related to consolidation of traumatic memories. In this context, hypnotic recall of anxiety memories in 10 patients, simultaneously with ECG measurement was performed. The same measurement was performed during control cognitive task in 8 anxiety patients and 22 healthy controls. Nonlinear data analysis of ECG records indicates significant increase in the degree of chaos during retrieval of stressful memory in all the patients. The results suggest a role of chaotic neural dynamics during processing of anxiety-related stressful memories.

The pattern of anxiolytic and hypnotic management by Australian general practice trainees.

PubMed

Holliday, Simon M; Morgan, Simon; Tapley, Amanda; Henderson, Kim M; Dunlop, Adrian J; van Driel, Mieke L; Spike, Neil A; McArthur, Lawrence A; Ball, Jean; Oldmeadow, Christopher J; Magin, Parker J

2017-03-01

Guidelines recommend anxiolytics and hypnotics (A/H) as second-line, short-term medications. We aimed to establish prevalence and associations of A/H prescribing by Australian general practice (GP) trainees. A cross-sectional analysis from a cohort study of vocational trainees from four GP Regional Training Providers during 2010-2013. General practice trainees act as independent practitioners (including for prescribing purposes) while having recourse to advice from a GP supervisor. Practice and trainee demographic data were collected as well as patient, clinical and educational data from 60 consecutive consultations of each trainee each training term. Analysis was at the level of individual problem managed, with the outcome factor being prescription of any anxiolytic or hypnotic. Overall, 645 registrars (response rate 94.0%) prescribed 68 582 medications in 69 621 consultations (with 112 890 problems managed). A/Hs were prescribed for 1.3% of problems managed and comprised 2.2% of all prescriptions. They were prescribed particularly for insomnia (28.2%) or anxiety (21.8%), but also for many 'off-label' indications. Significant associations of A/H prescriptions were: patient-level (greater age, Aboriginal and Torres Strait Islander status, English-speaking background, being new to the trainee but not to the practice); trainee-level (male) and consultation-level (longer duration, pre-existing problem, specialist referral not being made). Prescribing was significantly lower in one of the four Regional Training Providers. GP trainees, inconsistent with most guideline recommendations, prescribe A/Hs mainly as maintenance therapy to unfamiliar and older patients. Our results suggest that changes in management approaches are needed which may be facilitated by support for psychotherapeutic training. [Holliday SM, Morgan S, Tapley A, Henderson KM, Dunlop AJ, van Driel ML, Spike NA, McArthur LA, Ball J, Oldmeadow CJ, Magin PJ. The pattern of anxiolytic and hypnotic

Olprinone/dopamine combination for improving diaphragmatic fatigue in pentobarbital-anesthetized dogs.

PubMed

Fujii, Yoshitaka

2006-05-01

Diaphragmatic fatigue might contribute to the development of respiratory failure. In particular, the spontaneous, natural rate of phrenic nerve discharge occurs mainly in low-frequency ranges making low-frequency fatigue clinically important in both humans and animals. Olprinone, a phosphodiesterase 3 inhibitor, improves contractility in fatigued diaphragm, but is also associated with hypotension. Dopamine might be used concomitantly for treating related hypotension. The purpose of the study was to assess the effect of olprinoneplus dopamine on diaphragmatic fatigue in pentobarbital-anesthetized dogs. This nonblinded study was conducted at the Department ofAnesthesiology, Institute of Clinical Medicine, Tsukuba, Japan. Diaphragmatic fatigue (assessed by a decrease in diaphragmatic contractility) was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 minutes. Immediately after the fatigue-producing period, groups 2, 3, and 4 received an initial 10 μg/kg dose of olprinone. Group 2 then received maintenance olprinone of 0.3 μg/kg · min; group 3 received maintenance olprinone 0.3 μg/kg · min plus dopamine 2 μg/kg · min; and group 4 received maintenance olprinone 0.3 μg/kg · min plus dopamine 5 μg/kg · min. Group 1 received no study drug. Olprinone and dopamine were administered IV for 30 minutes. Diaphragmatic contractility was assessed by measuring the maximal transdiaphragmatic pressure (Pdi) generated by test stimuli after airway occlusion at functional residual capacity. Hypotension induced by the study drugs was defined as a >10 mm Hg decrease in mean arterial pressure (MAP), calculated by diastolic pressure plus ⅓ pulse pressure, from baseline. Twenty-eight mongrel dogs (18 males and 10 females, weighing 10-15 kg)were used in the study; 7 dogs were randomly assigned to each treatment group. When fatigue was established in each group, mean (SD) Pdi at low-frequency (20 Hz) stimulation

Sales of tranquillizers, hypnotics/sedatives and antidepressants and their relationship with underprivileged area score and mortality and suicide rates.

PubMed

Sundquist, J; Ekedahl, A; Johansson, S E

1996-01-01

This study analyses the correlation between the Swedish underprivileged area score and sales of tranquillizers, hypnotics/sedatives, neuroleptics and antidepressants, and the correlation between these sales and mortality and suicide rates, with the aim of using sales data to identify areas with poor socioeconomic conditions. Southern Sweden, 33 municipalities in Skåne, 1987 and 1994. Ecological study. Determined and undetermined cases of suicide were taken from the local death register for the years 1987-1993. Suicide rates (determined and undetermined cases) were calculated as the ratio between observed and expected number of suicides. Mortality for people aged 20-64 years was calculated from life tables for the decade 1981-1990. The underprivileged area score was calculated for municipalities using the proportion of persons in the following groups: elderly living alone, under 5 years of age, one-parent families, unskilled, unemployed, living in crowded households, those moving house in the previous year, and ethnic groups. After transformation (square root of arc sine) and standardization, each of the eight variables was weighted by the British general practitioners average weighting and added to give the underprivileged area score. The selection of the eight variables was based on general practitioners' perceptions of the effect of the social characteristics of the populations in their respective residential areas on their workload or pressure on services. The total drug sales figures for tranquillizers, hypnotics/sedatives, neuroleptics and antidepressants are expressed in Defined Daily Doses per 1000 inhabitants per day. The relationship between these variables was analysed using Pearson's correlation coefficient. There was a moderate correlation (0.41-0.68) between the sales expressed as in Defined Daily Doses per 1000 inhabitants per day of tranquillizers and hypnotics/sedatives and underprivileged area score. Furthermore, the sales of tranquillizers and

People with insomnia: experiences with sedative hypnotics and risk perception.

PubMed

Cheung, Janet M Y; Bartlett, Delwyn J; Armour, Carol L; Ellis, Jason G; Saini, Bandana

2016-08-01

Sedative hypnotics form an important part of managing insomnia and are recommended for short-term use. It is standard practice for clinicians to inform the patient to use medications only 'when required', but the use of these medications is often chronic. Little is known about the impact of standard labelling/instructions on promoting appropriate medication use for managing insomnia. To explore patient medication-taking beliefs, experiences and behavioural practices relating to the use of pharmacological/complementary sleep aids for insomnia. Specialist sleep/psychology clinics and the general community in Sydney, Australia. Semi-structured interviews were conducted with 51 people with insomnia using a schedule of questions to gauge their experiences, beliefs and current practices relating to insomnia medication use. Interviews were audio-recorded, transcribed verbatim and subjected to Framework Analysis to identify emergent themes. Participants held distinctive views about the safety and efficacy of complementary and pharmacological agents but do not intuitively turn to medications to resolve their sleep complaint. Medication use was affirmed through tangible medication-taking cues due to the ambivalence in current instructions and labelling. Practices such as dosage modification, medication substitution and delaying medication use might be important drivers for psychological dependence. Current labelling and instructions do not necessarily promote the quality use of sedative hypnotics due to the variability in patient interpretations. Clarifying the timing, quantity and frequency of medication administration as well as insomnia symptom recognition would play a significant role in optimizing the role of pharmacotherapy in the management of insomnia. © 2015 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

[Effects of afloqualone, a centrally acting muscle relaxant, on the sleep-wakefulness cycle in cats with chronically implanted electrodes (author's transl)].

PubMed

Kojima, M; Kudo, Y; Ishida, R

1981-11-01

The present study was carried out to elucidate whether or whether not afloqualone has a hypnotic action because of its similarity in chemical structure to methaqualone. In the sleep-wakefulness cycles during the 8-hour observation period (9:00-17:00), afloqualone increased the percentages of resting (REST) and slow wave light sleep (SWLS) stages at a dose of 25 mg/kg (p.o.), producing a moderate muscle relaxation. Even at a dose of 50 mg/kg (p.o.) where a marked muscle relaxation was produced, afloqualone had no influence on the percentage of slow wave deep sleep (SWDS) stage, though it increased the percentages of SWLS and decreased the percentages of awake (AWK), REST and fast wave sleep (FWS) stages. On the other hand, tolperisone . HCl, chlormezanone, methaqualone and pentobarbital . Na, used as the reference drugs, all increased the percentage of SWDS stage, but either decreased or had no effect on the percentages of the other four stages at pharmacologically effective doses. From these results it was concluded that afloqualone seems to be devoid of a hypnotic action and has different effects on the sleep-wakefulness cycle than those of both the hypnotics and the other muscle relaxants used.

The Role of Expectancy in Eliciting Hypnotic Responses as a Function of Type of Induction.

ERIC Educational Resources Information Center

Kirsch, Irving; And Others

1984-01-01

Examined the relationship between expectancy and suggestibility in hypnosis as a function of type of induction (N=100). Results showed subjects were able to predict their responses to a cognitive skill induction with great accuracy but were not very accurate in predicting responses to a hypnotic trance induction. (JAC)

A single dose of hypnotic corrects sleep and EEG abnormalities in symptomatic Huntington's disease mice.

PubMed

Kantor, Sandor; Varga, Janos; Morton, A Jennifer

2016-06-01

Sleep and electroencephalogram abnormalities are prominent early features of Huntington's disease (HD) that typically appear before the onset of characteristic motor symptoms. The changes in sleep and electroencephalogram seen in HD patients are largely recapitulated in mouse models of HD such as transgenic R6/2 lines. To test whether or not drugs with hypnotic properties can correct the sleep and electroencephalogram abnormalities seen in HD mice, we treated male wild-type (WT; N = 7) and R6/2 mice (N = 9) acutely with intraperitoneal injections of vehicle, zolpidem (5, 10 or 20 mg/kg) or amitriptyline (5, 10 or 20 mg/kg), and then monitored their sleep-wake behavior. In R6/2 mice, both zolpidem and amitriptyline suppressed the abnormally high REM sleep amount and electroencephalographic gamma (30-46 Hz) oscillations in a dose-dependent manner. Amitriptyline's effect on sleep was similar in both genotypes, whereas zolpidem showed significant genotype differences. Zolpidem exerted a strong hypnotic effect in WT mice by increasing electroencephalographic delta power, doubling the mean bout duration and the total amount of non-rapid eye movement sleep. However, no such effect was seen in R6/2 mice. Our study demonstrates that the pathophysiological changes seen in sleep and electroencephalogram are not 'hard-wired' in HD brain and can be reversed even at late stages of the disease. The diminished hypnotic effect of zolpidem suggests that the GABAergic control of sleep-wake states is impaired in HD mice. A better understanding of the neurochemical basis underlying these abnormalities should lead to more effective and rational therapies for HD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Damned if you do, damned if you don't? The Lundbeck case of pentobarbital, the guiding principles on business and human rights, and competing human rights responsibilities.

PubMed

Buhmann, Karin

2012-01-01

In 2011 it emerged that to induce the death penalty, United States authorities had begun giving injections of pentobarbital, a substance provided by Danish pharmaceutical company Lundbeck. Lundbeck's product pentobarbital is licensed for treatment of refractory forms of epilepsy and for usage as an anaesthetic, thus for a very different purpose. The Lundbeck case offers a difficult, but also interesting Corporate Social Responsibility (CSR) dilemma between choices facing a pharmaceutical company to stop the distribution of a medical substance in order to avoid complicity in human rights violations, or to retain distribution of the substance in order not to impede access to the medicine for those patients who need it. The dilemma arose at a time when the United Nations (UN) Secretary General's Special Representative on Business and Human Rights, Professor John Ruggie, was finalizing a set of Guiding Principles to operationalize recommendations on business and human rights that he had presented to the UN Human Rights Council in 2008. The article discusses the dilemma in which Lundbeck was placed in from the perspective of the Guiding Principles on business and human rights and the 2008 Protect, Respect, Remedy UN Framework. The analysis seeks to assess what guidance may be gauged from the Guiding Principles in relation to the dilemma at hand and discusses the adequacy the Guiding Principles for dealing with acute human rights dilemmas of conflicting requirements in which a decision to avoid one type of violation risks causing violation of another human right. The article concludes by drawing up perspectives for further development of guidance on implementation of the UN Framework that could be considered by the newly established Working Group on Business and Human Rights and related UN bodies. © 2012 American Society of Law, Medicine & Ethics, Inc.

Neo-adjuvant chemotherapy with cisplatin induces low expression of NMDA receptors and postoperative cognitive impairment.

PubMed

Cheng, Jing; Liu, Xiaoqing; Cao, Longhui; Zhang, Tianhua; Li, Huiting; Lin, Wenqian

2017-01-10

Whether Neo-adjuvant chemotherapy can affect patients' postoperative brain function is not clear. In this study, we investigated the effect of preoperative cisplatin treatment on postoperative cognitive function and its possible mechanism in rats. Moreover, we also tested whether the NMDAR inhibitor memantine could attenuate cisplatin-induced alterations. 12-month-oldSprague-Dawley rats randomly received an intraperitoneal injection of either cisplatin once a week at a dose of 3mg/kg for three consecutive weeks or an equivalent volume of normal saline. After the injections, the normal saline injection group was divided into 3 groups (n=5 each): a normal saline group (group S), normal saline+pentobarbital group (group SP), and normal saline+pentobarbital+operation group (group SPO).The cisplatin injection group was divided into 3 groups: a cisplatin group (group C), cisplatin+pentobarbital group (group CP), and cisplatin+pentobarbital+operation group (group CPO).Rats in the group SP, SPO,CP and CPO were anaesthetized with sodium pentobarbital and then the SPO and CPO groups underwent a simple laparotomy operation. The effects of memantine were tested through two additional groups of rats (cisplatin+memantine group (group CM) and cisplatin+pentobarbital+operation+memantine group (group CPOM)). A Morris water maze test was performed to evaluate the spatial learning and memory ability five days after anesthesia or operation. After the test, the hippocampi were removed for detection of the expression of NMDAR by western bloting. The relevant protein expression levels of PSD95 and ERK1/2 were detected by western blot analysis. Rats treated with cisplatin had a longer mean escape latency and spent a shorter amount of time in the target quadrant than did the normal saline injection rats. Furthermore, the protein expression levels of NMDA receptors, PSD95 and ERK1/2 were decreased in cisplatin group and memantine could up-regulate their expression. These results suggest

K+ channel TASK-1 knockout mice show enhanced sensitivities to ataxic and hypnotic effects of GABA(A) receptor ligands.

PubMed

Linden, Anni-Maija; Aller, M Isabel; Leppä, Elli; Rosenberg, Per H; Wisden, William; Korpi, Esa R

2008-10-01

TASK two-pore-domain leak K(+) channels occur throughout the brain. However, TASK-1 and TASK-3 knockout (KO) mice have few neurological impairments and only mildly reduced sensitivities to inhalational anesthetics, contrasting with the anticipated functions and importance of these channels. TASK-1/-3 channel expression can compensate for the absence of GABA(A) receptors in GABA(A) alpha6 KO mice. To investigate the converse, we analyzed the behavior of TASK-1 and -3 KO mice after administering drugs with preferential efficacies at GABA(A) receptor subtypes: benzodiazepines (diazepam and flurazepam, active at alpha1betagamma2, alpha2betagamma2, alpha3betagamma2, and alpha5betagamma2 subtypes), zolpidem (alpha1betagamma2 subtype), propofol (beta2-3-containing receptors), gaboxadol (alpha4betadelta and alpha6betadelta subtypes), pregnanolone, and pentobarbital (many subtypes). TASK-1 KO mice showed increased motor impairment in rotarod and beam-walking tests after diazepam and flurazepam administration but not after zolpidem. They also showed prolonged loss of righting reflex induced by propofol and pentobarbital. Autoradiography indicated no change in GABA(A) receptor ligand binding levels. These altered behavioral responses to GABAergic drugs suggest functional up-regulation of alpha2beta2/3gamma2 and alpha3beta2/3gamma2 receptor subtypes in TASK-1 KO mice. In addition, female, but not male, TASK-1 KO mice were more sensitive to gaboxadol, suggesting an increased influence of alpha4betadelta or alpha6betadelta subtypes. The benzodiazepine sensitivity of TASK-3 KO mice was marginally increased. Our results underline that TASK-1 channels perform such key functions in the brain that compensation is needed for their absence. Furthermore, because inhalation anesthetics act partially through GABA(A) receptors, the up-regulation of GABA(A) receptor function in TASK-1 KO mice might mask TASK-1 channel's significance as a target for inhalation anesthetics.

Enhancing witness memory with techniques derived from hypnotic investigative interviewing: focused meditation, eye-closure, and context reinstatement.

PubMed

Wagstaff, Graham F; Wheatcroft, Jacqueline M; Caddick, Andrea M; Kirby, Lara J; Lamont, Elizabeth

2011-04-01

Due to several well-documented problems, hypnosis as a forensic interviewing tool has been largely replaced by the cognitive interview; however, the latter is problematic in time and complexity. This article builds on previous research showing that some procedures used in traditional hypnotic forensic interviewing might still be useful in developing alternative procedures for use in investigative interviewing. Two experiments are described that include a focused meditation with eye-closure technique with similarities to conventional hypnotic induction but without the label of hypnosis. In the first, focused meditation was comparable to a context reinstatement, or revivification, technique in facilitating memory in children aged 6 to 7 without increasing errors or inflating confidence. In the second, when used in combination with context reinstatement, focused meditation was resistant to the effects of misleading information in adults. Implications are discussed.

Effects of some antipsychotics and a benzodiazepine hypnotic on the sleep-wake pattern in an animal model of schizophrenia.

PubMed

Ishida, Takayuki; Obara, Yoshihito; Kamei, Chiaki

2009-09-01

We studied the effects of antipsychotics and a hypnotic on sleep disturbance in schizophrenia using an animal model of the disease. Electrodes for the electroencephalogram (EEG) and electromyogram (EMG) were chronically implanted into the cortex and the dorsal neck muscle of rats. EEG and EMG were recorded with an electroencephalograph for 6 h (10:00 - 16:00). SleepSign ver. 2.0 was used for EEG and EMG analysis. Haloperidol and olanzapine had an antagonizing effect on the increases in sleep latency and total awake time and the decrease in total non-rapid eye movement (NREM) sleep time induced by MK-801. Olanzapine also antagonized the decrease in total rapid eye movement (REM) sleep time induced by MK-801. Aripiprazole antagonized only the increase in sleep latency induced by MK-801, whereas, risperidone, quetiapine, and flunitrazepam had no effect in the changes of sleep-wake pattern induced by MK-801. Olanzapine increased delta activity and decreased beta activity during NREM sleep. In contrast, flunitrazepam had an opposite effect. It was clarified that haloperidol and olanzapine were effective for decrease of sleep time in this animal model of schizophrenia. In addition, aripiprazole showed a sleep-inducing effect in schizophrenia model rat. On the other hand, flunitrazepam showed no beneficial effect on sleep disturbance in schizophrenia model rat.

Metabolism of anxiolytics and hypnotics: benzodiazepines, buspirone, zoplicone, and zolpidem.

PubMed

Chouinard, G; Lefko-Singh, K; Teboul, E

1999-08-01

1. The benzodiazepines are among the most frequently prescribed of all drugs and have been used for their anxiolytic, anticonvulsant, and sedative/hypnotic properties. Since absorption rates, volumes of distribution, and elimination rates differ greatly among the benzodiazepine derivatives, each benzodiazepine has a unique plasma concentration curve. Although the time to peak plasma levels provides a rough guide, it is not equivalent to the time to clinical onset of effect. The importance of alpha and beta half-lives in the actions of benzodiazepines is discussed. 2. The role of cytochrome P450 isozymes in the metabolism of benzodiazepines and in potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs is discussed. 3. Buspirone, an anxiolytic with minimal sedative effects, undergoes extensive metabolism, with hydroxylation and dealkylation being the major pathways. Pharmacokinetic interactions of buspirone with other coadministered drugs seem to be minimal. 4. Zopiclone and zolpidem are used primarily as hypnotics. Both are extensively metabolized; N-demethylation, N-oxidation, and decarboxylation of zopiclone occur, and zolpidem undergoes oxidation of methyl groups and hydroxylation of a position on the imidazolepyridine ring system. Zopiclone has a chiral centre, and demonstrates stereoselective pharmacokinetics. Metabolic drug-drug interactions have been reported with zopiclone and erythromycin, trimipramine, and carbamazepine. Reports to date indicate minimal interactions of zolpidem with coadministered drugs; however, it has been reported to affect the Cmax and clearance of chlorpromazepine and to decrease metabolism of the antiviral agent ritonavin. Since CYP3A4 has been reported to play an important role in metabolism of zolpidem, possible interactions with drugs which are substrates and/or inhibitors of that CYP isozyme should be considered.

Evaluation of the calcium-antagonist, antidiarrhoeic and central nervous system activities of Baccharis serraefolia.

PubMed

Tortoriello, J; Aguilar-Santamaría, L

1996-09-01

Baccharis serraefolia is a widely used plant to treat diarrhoea in Mexican traditional medicine. Although the methanolic extract of this plant has shown an important dose-dependent spasmolytic activity, its underlying mechanism has not been studied. In the present work, the methanolic extract of B. serraefolia significantly delayed the onset of tonic seizures induced by strychnine and pentylenetetrazol; besides, it diminished the death rate and number of animals that exhibited convulsions. It produced potentiation of the hypnotic effect of pentobarbital. Oral administration produced an inhibition of gastrointestinal transit in mice as effective as that produced by loperamide. As to the effect on smooth muscles, the active extract produced an inhibition of contraction induced electrically, which could not be reversed by naloxone. The calcium concentration-contraction curve showed a rightward displacement when the extract was added to isolated guinea pig ileum depolarized with high K+ and cumulative concentrations of Ca2+. The results suggest that the methanolic extract does not interact with classical opiate receptors and its effects, at least that produced on smooth muscle, may be due to a probable interference with calcium influx and/or calcium release from an intra-cellular store.

A study comparing the hypnotic efficacies and residual effects on actual driving performance of midazolam 15 mg, triazolam 0.5 mg, temazepam 20 mg and placebo in shiftworkers on night duty

DOT National Transportation Integrated Search

1988-11-01

The purpose of the study was to determine the hypnotic efficacy and residual effects of three hypnotics administered for the treatment of transient insomnia in the day-sleep of rotating shift workers. The average duration of day-sleep in rotating shi...

Dependence of pentobarbital kinetics upon the dose of the drug and its pharmacodynamic effects.

PubMed

Kozlowski, K H; Szaykowski, A; Danysz, A

1977-01-01

Pentobarbital (PB), at dose range of 20--50 mg/kg, displays in rabbits non-linear, dose-dependent kinetics. Pharmacokinetics parameters of drug elimination depend largely upon the dose, while the distribution phase is dose-independent. The rate of disappearance of PB from the central compartment (plasma) decreases with the increase of the dose. The analysis of pharmacodynamic parameters has shown that this dose-dependent retardation of PB elimination is probably caused by an impairment of metabolic processes, resulting from disturbance of the circulatory system. A close correlation has been found between the hypotensive effect of PB and the elimination constant, k13, and also between the hypotensive effect and beta.Vd(extrap), a coefficient proportional to the rate of metabolism of PB [23, 29]. The results indicate the necessity of considering the changes in the functional state of the organism, related to the action of a drug, in pharmacokinetic studies.

Simultaneous analysis by Quadrupole-Orbitrap mass spectrometry and UHPLC-MS/MS for the determination of sedative-hypnotics and sleep inducers in adulterated products.

PubMed

Lee, Ji Hyun; Park, Han Na; Choi, Ji Yeon; Kim, Nam Sook; Park, Hyung-Joon; Park, Seong Soo; Baek, Sun Young

2017-12-01

Adulterated products are continuously detected in society and cause problems. In this study, we developed and validated a method for determining synthetic sedative-hypnotics and sleep inducers, including barbital, benzodiazepam, zolpidem, and first-generation antihistamines, in adulterated products using Quadrupole-Orbitrap mass spectrometry and ultrahigh performance liquid chromatography with tandem mass spectrometry. In Quadrupole-Orbitrap mass spectrometry analysis, target compounds were confirmed using a combination of retention time, mass tolerance, mass accuracy, and fragment ions. For quantification, several validation parameters were employed using ultrahigh performance liquid chromatography with tandem mass spectrometry. The limit of detection and limit of quantitation was 0.05-53 and 0.17-177 ng/mL, respectively. The correlation coefficient for linearity was more than 0.995. The intra- and interassay accuracies were 86-110 and 84-111%, respectively. Their precision values were evaluated as within 4.0 (intraday) and 10.7% (interday). Mean recoveries of target compounds in adulterated products ranged from 85 to 116%. The relative standard deviation of stability was less than 10.7% at 4°C for 48 h. The 144 adulterated products obtained over 3 years (2014-2016) from online and in-person vendors were tested using established methods. After rapidly screening with Quadrupole-Orbitrap mass spectrometry, the detected samples were quantified using ultrahigh performance liquid chromatography with tandem mass spectrometry. Two of them were adulterated with phenobarbital. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

First Trimester Exposure to Anxiolytic and Hypnotic Drugs and the Risks of Major Congenital Anomalies: A United Kingdom Population-Based Cohort Study

PubMed Central

Ban, Lu; West, Joe; Gibson, Jack E.; Fiaschi, Linda; Sokal, Rachel; Doyle, Pat; Hubbard, Richard; Smeeth, Liam; Tata, Laila J.

2014-01-01

Background Despite their widespread use the effects of taking benzodiazepines and non-benzodiazepine hypnotics during pregnancy on the risk of major congenital anomaly (MCA) are uncertain. The objectives were to estimate absolute and relative risks of MCAs in children exposed to specific anxiolytic and hypnotic drugs taken in the first trimester of pregnancy, compared with children of mothers with depression and/or anxiety but not treated with medication and children of mothers without diagnosed mental illness during pregnancy. Methods We identified singleton children born to women aged 15–45 years between 1990 and 2010 from a large United Kingdom primary care database. We calculated absolute risks of MCAs for children with first trimester exposures of different anxiolytic and hypnotic drugs and used logistic regression with a generalised estimating equation to compare risks adjusted for year of childbirth, maternal age, smoking, body mass index, and socioeconomic status. Results Overall MCA prevalence was 2.7% in 1,159 children of mothers prescribed diazepam, 2.9% in 379 children with temazepam, 2.5% in 406 children with zopiclone, and 2.7% in 19,193 children whose mothers had diagnosed depression and/or anxiety but no first trimester drug exposures. When compared with 2.7% in 351,785 children with no diagnosed depression/anxiety nor medication use, the adjusted odds ratios were 1.02 (99% confidence interval 0.63–1.64) for diazepam, 1.07 (0.49–2.37) for temazepam, 0.96 (0.42–2.20) for zopiclone and 1.27 (0.43–3.75) for other anxiolytic/hypnotic drugs and 1.01 (0.90–1.14) for un-medicated depression/anxiety. Risks of system-specific MCAs were generally similar in children exposed and not exposed to such medications. Conclusions We found no evidence for an increase in MCAs in children exposed to benzodiazepines and non-benzodiazepine hypnotics in the first trimester of pregnancy. These findings suggest that prescription of these drugs during early

Hypnosis and belief: A review of hypnotic delusions.

PubMed

Connors, Michael H

2015-11-01

Hypnosis can create temporary, but highly compelling alterations in belief. As such, it can be used to model many aspects of clinical delusions in the laboratory. This approach allows researchers to recreate features of delusions on demand and examine underlying processes with a high level of experimental control. This paper reviews studies that have used hypnosis to model delusions in this way. First, the paper reviews studies that have focused on reproducing the surface features of delusions, such as their high levels of subjective conviction and strong resistance to counter-evidence. Second, the paper reviews studies that have focused on modelling underlying processes of delusions, including anomalous experiences or cognitive deficits that underpin specific delusional beliefs. Finally, the paper evaluates this body of research as a whole. The paper discusses advantages and limitations of using hypnotic models to study delusions and suggests some directions for future research. Copyright © 2015 Elsevier Inc. All rights reserved.

Metacognition of agency is reduced in high hypnotic suggestibility.

PubMed

Terhune, Devin B; Hedman, Love R A

2017-11-01

A disruption in the sense of agency is the primary phenomenological feature of response to hypnotic suggestions but its cognitive basis remains elusive. Here we tested the proposal that distorted volition during response to suggestions arises from poor metacognition pertaining to the sources of one's control. Highly suggestible and control participants completed a motor task in which performance was reduced through surreptitious manipulations of cursor lag and stimuli speed. Highly suggestible participants did not differ from controls in performance or metacognition of performance, but their sense of agency was less sensitive to cursor lag manipulations, suggesting reduced awareness that their control was being manipulated. These results indicate that highly suggestible individuals have aberrant metacognition of agency and may be a valuable population for studying distortions in the sense of agency. Copyright © 2017 Elsevier B.V. All rights reserved.

A hypnotically mediated guided imagery intervention for intrusive imagery: creating ground for figure.

PubMed

Appel, P R

1999-04-01

Intrusive imagery can be seen as a cognitive dysfunction in the assimilation and accommodation of the psychological material represented by those images. From a gestalt psychological perspective, the intrusive image represents a figure without a ground that can provide meaning and context. Hypnotically mediated guided imagery interventions can be used to create a ground for the rogue image that metaphorically is an unassimilated figure; and thus allow for the creation of a new cognitive scheme. Four case examples are presented as well as a model for the intervention.

Therapy of vaginismus by hypnotic desensitization.

PubMed

Fuchs, K

1980-05-01

Fear and anxiety are of tremendous importance in the production and maintenance of a symptom. Vaginismus, as a reaction of avoidance of an anxiety-producing situation, is readily amenable to treatment by systematic desensitization. This may proceed mainly in two ways: "in vitro" or "in vivo." In order to strengthen and speed up the densensitization process, we used hypnotic techniques in a dynamic approach. The "in vitro" treatment proceeds with imagery, under hypnosis, of an "anxiety hierarchy" of increasingly erotic and sexually intimate situations which will be reproduced at home with the partner, until sexual intercourse is achieved. In the "in vivo" method the patient learns self-hypnosis and then inserts in the vagina first a finger, and then Hegar dilators of gradually increasing sizes. The partner, the patient, and the physician will then successively proceed to insertion, forming a team-referred work situation. This continues until the "female superior position," practiced first with the largest dilator, is reproduced at home by intercourse. Between 1965 and 1974 we treated 71 women with this method. Good results were obtained in 16 of 18 by the "in vitro" technique and in 53 of 54 by the "in vivo" technique. One patient was referred from the "in vitro" group to the "in vivo" group. In follow-up of 2 to 5 years there was no relapse or symptom substitution.

[Trends in the consumption of anxiolytic and hypnotic drugs in a Colombian population].

PubMed

Machado-Alba, Jorge Enrique; Alzate-Carvajal, Verónica; Jimenez-Canizales, Carlos Eduardo

2015-01-01

In Latin America, psychotropic medications are the third most marketed drug group, especially antidepressants (35%) and anxiolytics (5%). The objective of this study was to determine the trends in the consumption and the costs of anxiolytic and hypnotic drugs in a population of patients enrolled in the Health System of Colombia. A descriptive, observational study was performed using the data recorded inprescriptions for any anxiolytic or hypnotic drug prescribed to outpatients in the period between January 2008 and December 2013 in a population of 3.5 million people. Sociodemographic, pharmacological variables, overall costs, and cost per thousand inhabitants per day (CHD), were also recorded. The number of patients who received the drugs studied varied from 11,097 to 19,231 between 2008 and 2013. The most used drugs were clonazepam (44.1% of formulations), alprazolam (31.2%), and lorazepam (13.2%). The invoiced value of anxiolytics increased from US$ 207,673.63 in 2008 to US$ 488,977 in 2013, an increase of 135.4%. The CHD was US$ 0.31 for benzodiazepines, and US$ 0.02 for zaleplon, zolpidem and zopiclone (Z drugs) for 2008, and US$ 0.36 and US$ 0.02 in 2013 respectively. The CHD declined after 2010 following the introduction of generic drugs. Patients receiving benzodiazepines in Colombia are mostly women, average age 55 years, with very low frequency in defined daily doses per thousand inhabitants when compared with other countries. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

[Physical performance and sedation: comparative study of the effects of a benzodiazepine (temazepam) and of a non-benzodiazepine hypnotic (zolpidem)].

PubMed

Gremion, G; Sutter-Weyrich, C; Rostan, A; Forster, A

1992-09-01

It is well-known that many athletes experience some form of precompetition stress that may result in insomnia during the night before their competition. Yet, sleep withdrawal even if only partial, has a negative influence on performance, particularly when the type of exercise requires good psychomotor performance The purpose of the present study was to investigate whether the intake of a hypnotic drug would have negative effects on physical performance capacity. The authors have compared the effects of oral temazepam, a medium half-life benzodiazepine vs oral zolpidem, a short half-life non-benzodiazepine drug, vs placebo. A randomized double-blind trial was used to assess endurance, resistance, strength and coordination in 26 athletes. The results did not show any differences between the three groups, neither in physical performance characteristic nor in coordination. It is concluded that as regards the performance capacity, there is no risk for stressed athletes to use sleep inducers the night before their competition.

'Looking as little like patients as persons well could': hypnotism, medicine and the problem of the suggestible subject in late nineteenth-century Britain.

PubMed

Chettiar, Teri

2012-07-01

During the late nineteenth century, many British physicians rigorously experimented with hypnosis as a therapeutic practice. Despite mounting evidence attesting to its wide-ranging therapeutic uses publicised in the 1880s and 1890s, medical hypnosis remained highly controversial. After a decade and a half of extensive medical discussion and debate surrounding the adoption of hypnosis by mainstream medical professionals--including a thorough inquiry organised by the British Medical Association--it was decisively excluded from serious medical consideration by 1900. This essay examines the complex question of why hypnosis was excluded from professional medical practice by the end of the nineteenth century. Objections to its medical adoption rarely took issue with its supposed effectiveness in producing genuine therapeutic and anaesthetic results. Instead, critics' objections were centred upon a host of social and moral concerns regarding the patient's state of suggestibility and weakened 'will-power' while under the physician's hypnotic 'spell'. The problematic question of precisely how far hypnotic 'rapport' and suggestibility might depart from the Victorian liberal ideal of rational individual autonomy lay at the heart of these concerns. As this essay demonstrates, the hypnotism debate was characterised by a tension between physicians' attempts to balance their commitment to restore patients to health and pervasive middle-class concerns about the rapid and ongoing changes transforming British society at the turn of the century.

French Norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A.

PubMed

Anlló, Hernán; Becchio, Jean; Sackur, Jérôme

2017-01-01

The authors present French norms for the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A). They administered an adapted translation of Shor and Orne's original text (1962) to a group of 126 paid volunteers. Participants also rated their own responses following our translation of Kihlstrom's Scale of Involuntariness (2006). Item pass rates, score distributions, and reliability were calculated and compared with several other reference samples. Analyses show that the present French norms are congruous with the reference samples. Interestingly, the passing rate for some items drops significantly if "entirely voluntary" responses (as identified by Kihlstrom's scale) are scored as "fail." Copies of the translated scales and response booklet are available online.

[Effects of hypnotic and musical relaxation therapy on the treatment of the parents of children with cleft lip and/or palate].

PubMed

Yanyan, Zhang; Caixia, Gong; Xiaolin, Zhang; Ying, Chen; Jingchen, Xu; Pin, Ha; Jingtao, Li; Bing, Shi

2015-12-01

To evaluate the effectiveness of hypnotic and musical relaxation therapy and psychological consultation for parents of children with cleft lip and/or palate (CLP) and to provide a scientific basis of clinical-psychological treatment options. Sixty-six subjects with children with CLP participated in this study. The subjects were randomly assigned to a test group (n = 33) and a control group (n = 33). The test group was treated with hypnotic and musical relaxation therapy; the control group were subjected to psychological consultation. Anxiety and depression states were evaluated by using a self-rating anxiety scale (SAS) and a self-rating depression scale (SDS) before and after treatment was administered. 1) The test group demonstrated a significant decrease in SAS and SDS scores (t = 2.855, P < 0.01; t = 2.777, P < 0.01). The control group showed a significant decrease in the SAS score (t = 1.831, P < 0.05) but failed to show a significant change in the depression score (t = 0.909, P > 0.05). 2) The test group yielded a higher percentage of remission indicated by the SDS scores than the control group (test group = 75.76%; control group = 60.61%; P < 0.05). The test group also displayed a higher percentage of remission indicated by the SAS scores than the control group (test group = 78.79%, test group = 69.70%; P < 0.05). Hypnotic and musical relaxation therapy can more effectively reduce the scores of the anxiety and depression states of the parents of patients with cleft lip and/or palate than psychological consultation.

Long-Term Use of Benzodiazepines and Nonbenzodiazepine Hypnotics, 1999-2014.

PubMed

Kaufmann, Christopher N; Spira, Adam P; Depp, Colin A; Mojtabai, Ramin

2018-02-01

Clinical guidelines suggest that benzodiazepines (BZDs) and non-BZD hypnotics (NBHs) be used on a short-term basis. The authors examined trends in long-term BZD and NBH use from 1999 to 2014. Data included 82,091 respondents in the 1999-2014 waves of the National Health and Nutrition Examination Survey (NHANES). NHANES recorded medications used in the past 30 days on the basis of prescription bottles, and participants reported use duration. BZD and NBH use were categorized as short, medium, and long term, and time trends in use were assessed. BZD and NBH use increased from 1999 to 2014, driven by increases in medium- and long-term use, even after adjustment for age and race-ethnicity. In most years, only a fifth of current BZD or NBH users reported short-term use. Long-term BZD and NBH use has grown independent of U.S. demographic shifts. Monitoring of use is needed to prevent adverse outcomes.

Conscious/Unconscious Dissociation Induction: Increasing Hypnotic Performance With "Resistant" Clients.

PubMed

Lankton, Stephen

2016-10-01

Milton H. Erickson promoted several approaches to psychotherapy using hypnosis. In the last decades of his life, his work moved away from the use of redundant suggestion and a predominance of direct suggestion in favor of indirect suggestion. In addition, he frequently employed a type of storytelling (that has come to be called therapeutic metaphor) to indirectly convey learning. Another change that occurred during the last decade was his definition of the cause of a symptom. However, there were two important areas of his work that he did not change during his career. These two components of his work he did not change were his definition of a cure and the importance of a naturalistic induction. This article concerns his naturalistic approach to hypnotic induction and especially his use of conscious/unconscious dissociation in the induction process and how indirect suggestion and therapeutic binds can be used to facilitate that type of induction and a cure.

Improvement in bronchial hyper-responsiveness in patients with moderate asthma after treatment with a hypnotic technique: a randomised controlled trial.

PubMed Central

Ewer, T C; Stewart, D E

1986-01-01

A prospective, randomised, single blind, and controlled trial of a hypnotic technique was undertaken in 39 adults with mild to moderate asthma graded for low and high susceptibility to hypnosis. After a six week course of hypnotherapy 12 patients with a high susceptibility score showed a 74.9% improvement (p less than 0.01) in the degree of bronchial hyper-responsiveness to a standardised methacholine challenge test. Daily home recordings of symptoms improved by 41% (p less than 0.01), peak expiratory flow rates improved by 5.5% (p less than 0.01), and use of bronchodilators decreased by 26.2% (p less than 0.05). The improvement in bronchial hyper-reactivity occurred without a change in subjective appreciation of the degree of bronchoconstriction. A control group 17 patients and 10 patients undergoing treatment with low susceptibility to hypnosis had no change in either bronchial hyper-responsiveness or any of the symptoms recorded at home. This study shows the efficacy of a hypnotic technique in adult asthmatics who are moderately to highly susceptible to hypnosis. PMID:3094804

Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances.

PubMed

Revel, Florent G; Gottowik, Juergen; Gatti, Sylvia; Wettstein, Joseph G; Moreau, Jean-Luc

2009-06-01

Insomnia, the most common sleep disorder, is characterized by persistent difficulty in falling or staying asleep despite adequate opportunity to sleep, leading to daytime fatigue and mental dysfunction. As sleep is a sophisticated physiological process generated by a network of neuronal systems that cannot be reproduced in-vitro, pre-clinical development of hypnotic drugs requires in-vivo investigations. Accordingly, this review critically evaluates current and putative rodent models of insomnia which could be used to screen novel hypnotics. Only few valid insomnia models are currently available, although many experimental conditions lead to disturbance of physiological sleep. We categorized these conditions as a function of the procedure used to induce perturbation of sleep, and we discuss their respective advantages and pitfalls with respect to validity, feasibility and translational value to human research.

Translation, adaptation, and validation of the Stanford Hypnotic Clinical Scale in Puerto Rico.

PubMed

Deynes-Exclusa, Yazmin; Sayers-Montalvo, Sean K; Martinez-Taboas, Alfonso

2011-04-01

The only hypnotizability scale that has been translated and validated for the Puerto Rican population is the Barber Suggestibility Scale (BSS). In this article, the Stanford Hypnotic Clinical Scale (SHCS) was translated and validated for this population. The translated SHCS ("Escala Stanford de Hipnosis Clinica" [ESHC]) was administered individually to 100 Puerto Rican college students. There were no significant differences found between the norms of the original SHCS samples and the Spanish version of the SHCS. Both samples showed similar distributions. The Spanish version's internal reliability as well as the item discrimination index were adequate. The authors conclude that the ESHC is an adequate instrument to measure hypnotizability in the Puerto Rican population.

Seeing Blue As Red: A Hypnotic Suggestion Can Alter Visual Awareness of Colors.

PubMed

Kallio, Sakari; Koivisto, Mika

2016-01-01

Some highly hypnotizable individuals have reported changes in objects' color with suggestions given in normal waking state. However, it is not clear whether this occurs only in their imagination. The authors show that, although subjects could imagine colors, a posthypnotic suggestion was necessary for seeing altered colors, even for a hypnotic virtuoso. She reported posthypnotic color alterations also selectively in response to specific target shapes in briefly presented object arrays. Surprisingly, another highly hypnotizable person showed a very different pattern of results. The control participants could not simulate virtuosos' results by applying cognitive strategies. The results imply that hypnosis can alter the functioning of automatic visual processes but only in some of the most hypnotizable individuals.

‘Looking as Little Like Patients as Persons Well Could’: Hypnotism, Medicine and the Problem of the Suggestible Subject in Late Nineteenth-Century Britain

PubMed Central

Chettiar, Teri

2012-01-01

During the late nineteenth century, many British physicians rigorously experimented with hypnosis as a therapeutic practice. Despite mounting evidence attesting to its wide-ranging therapeutic uses publicised in the 1880s and 1890s, medical hypnosis remained highly controversial. After a decade and a half of extensive medical discussion and debate surrounding the adoption of hypnosis by mainstream medical professionals – including a thorough inquiry organised by the British Medical Association – it was decisively excluded from serious medical consideration by 1900. This essay examines the complex question of why hypnosis was excluded from professional medical practice by the end of the nineteenth century. Objections to its medical adoption rarely took issue with its supposed effectiveness in producing genuine therapeutic and anaesthetic results. Instead, critics’ objections were centred upon a host of social and moral concerns regarding the patient’s state of suggestibility and weakened ‘will-power’ while under the physician’s hypnotic ‘spell’. The problematic question of precisely how far hypnotic ‘rapport’ and suggestibility might depart from the Victorian liberal ideal of rational individual autonomy lay at the heart of these concerns. As this essay demonstrates, the hypnotism debate was characterised by a tension between physicians’ attempts to balance their commitment to restore patients to health and pervasive middle-class concerns about the rapid and ongoing changes transforming British society at the turn of the century. PMID:23002303

Effectiveness of a direct-to-consumer written health education program in the reduction of benzodiazepine and sedative-hypnotic use in an elderly population at a single Veterans Affairs medical center

PubMed Central

2018-01-01

Introduction: The use of benzodiazepines and sedative-hypnotics in the elderly is associated with a significant risk of delirium, falls, fractures, cognitive impairment, and motor vehicle accidents. This quality improvement project applies a direct-to-consumer intervention to an elderly veteran population to reduce the use of these medications. Methods: Patients aged 75 and older currently taking a benzodiazepine and/or a sedative-hypnotic were included in the project. Direct-to-consumer education intervention letters were mailed to patients within 30 days of their next appointment. Their providers were emailed a questionnaire after the patient's appointment. Providers were asked if the letter prompted a conversation regarding medication use, whether the provider initiated discussion regarding a taper, and whether a specific taper plan was developed. Medical records were reviewed to determine if a reduction in dose or discontinuation occurred. Results: Fifty-nine direct-to-consumer education letters were mailed to the patients. Follow-up questionnaires were e-mailed to 44 providers, and 27 providers responded. Twenty-two percent of patients had their benzodiazepine and/or sedative hypnotic dose reduced or discontinued after their follow-up appointment. Sixty-seven percent of veterans initiated a conversation with their provider regarding their medication with 74% of providers discussing dose reduction. Fifty-six percent of recipients developed a specific taper plan with their provider. Discussion: The data from this project suggests that direct-to-consumer patient education can reduce the exposure to benzodiazepines and sedative-hypnotics in an elderly veteran population. More data is needed on larger populations to further explore the benefit of direct-to-consumer interventions.

Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

PubMed Central

Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

2013-01-01

The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

PubMed

Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

2012-04-15

Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine.

The effects of benzodiazepine (triazolam), cyclopyrrolone (zopiclone) and imidazopyridine (zolpidem) hypnotics on the frequency of hippocampal theta activity and sleep structure in rats.

PubMed

Yoshimoto, M; Higuchi, H; Kamata, M; Yoshida, K; Shimizu, T; Hishikawa, Y

1999-01-01

In order to investigate the relative efficacy and safety of zopiclone and zolpidem, we compared the effects of higher doses of zopiclone and zolpidem on the frequency of hippocampal theta activity and sleep structure with that of triazolam. Rats were divided into triazolam treatment group (1 mg/kg, 5 mg/kg), zopiclone treatment group (20 mg/kg, 100 mg/kg) and zolpidem treatment group (20 mg/kg, 100 mg/kg). Rats were injected intraperitoneally with these drugs or their vehicle. Polygraphic sleep recording and visual frequency analysis of the hippocampal EEG activity in REM sleep were carried out for 6 h after each injection. Zolpidem, unlike triazolam and zopiclone, had a much milder reducing-effect on the frequency of hippocampal theta activity and suppressing-effect on REM sleep. These results suggest that zolpidem may prove to be a safer hypnotic drug which has fewer or milder side effects than are benzodiazepine and cyclopyrrolone hypnotics.

Trends in prescribing of sedative-hypnotic medications in the United States: 1993–2010

PubMed Central

Kaufmann, Christopher N.; Spira, Adam P.; Alexander, Caleb; Rutkow, Lainie; Mojtabai, Ramin

2016-01-01

PURPOSE Non-benzodiazepine receptor agonists (nBZRAs) were developed as an alternative to benzodiazepines (BZDs) to treat insomnia. Little is known how the introduction of nBZRAs influenced trends in BZD prescribing. We examined BZD and nBZRA prescribing trends from 1993 to 2010. METHODS We used the National Ambulatory Medical Care Survey to examine 516,118 patient visits between 1993 and 2010. We categorized visits as BZD, nBZRA, or BZD+nBZRA visits based on medications prescribed each visit and applied linear probability regression models to assess trends in visits. RESULTS Increases were observed in proportions of visits that were BZD (2.6% in 1993 to 4.4% in 2010, p<0.001) and nBZRA (0% to 1.4%, p<0.001). Increases in BZD visits were primarily after 2002, with prescribing in the preceding years remaining relatively stable. We also found increases in BZD+nBZRA visits (0% to 0.4%, p<0.001). Among patients with sleep disorders, there was an increase in nBZRA visits (2.3% to 13.7%, p<0.001), and decline in BZD visits (23.5% to 10.8%, p=0.015). Just under a third (30.8%) of any-sedative hypnotic visits were for adults aged 65+, among whom increases in BZD, nBZRA, and BZD+nBZRA visits were observed across the study period. CONCLUSIONS There were increases in prescribing of nBZRAs between 1993 and 2010. Increases in prescribing of BZDs were also observed, especially after 2002. The introduction of nBZRAs likely resulted in declines in BZD prescribing among those with a sleep disorder, but not other groups. Delivery of behavioral treatments should be encouraged to avert adverse outcomes associated with sedative-hypnotic use. PMID:26711081

[Foshouningshen decoction improves sleeping via the serotonergic system in a rat model of insomnia].

PubMed

Huang, Jie-Cong; Xie, Wei; Deng, Ning; Liang, Wen-Lin; Hu, Dong-Rong; Hong, Yu; Zhou, Yang

2017-08-20

To evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HT 1A R) in the hippocampus in a rat model of insomnia. Male KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HT 1A R protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively. In the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (P<0.05); in the test with a threshold dose of sodium pentobarbital, treatment with moderate- and high-dose FSNSD resulted in significantly prolonged sleeping time (P<0.01) and shortened sleep latency (P<0.05) in the mice. The rats in insomnia model group showed increased total distance in open field test (P<0.05) with significantly decreased content of 5-HT (P<0.01) and expressions of 5-HT 1A R protein and mRNA in the hippocampus (P<0.01). Treatment of the rats with estazolam or high-dose FSNSD obviously decreased the total distance in open

Diagnosis and hypnotic treatment of an unusual case of hysterical amnesia.

PubMed

Iglesias, Alex; Iglesias, Adam

2009-10-01

This article reports on the use of hypnosis to facilitate the diagnostic process and the treatment of an unusual case of adult psychogenic amnesia. An Iraqi citizen living in the U.S. developed an atypical case of Dissociative Amnesia, Systematized type, post-automotive collision. The amnesia presented with features encompassing complete loss of the patient's native language. Dissociation theory as a conceptualization of hysterical reactions was employed as the basis in the formulation of this case. The differential diagnosis was facilitated by the Hypnotic Diagnostic Interview for Hysterical Disorders (HDIHD) Adult Form, an interview tool specifically designed for cases such as this. Treatment consisted exclusively of ego strengthening and time projection approaches in hypnosis. It was hypothesized that, as the coping capacities became more viable, the dissociative symptoms would remiss. After 6 weekly visits the patient regained complete command of his native language. Follow-up at 6 months indicated that the patient remained devoid of symptoms.

The investigation of immunoprotective and sedative hypnotic effect of total polysaccharide from Suanzaoren decoction by serum metabonomics approach.

PubMed

Niu, Xiaoyi; He, Bosai; Du, Yiyang; Sui, Zhenyu; Rong, Weiwei; Wang, Xiaotong; Li, Qing; Bi, Kaishun

2018-06-01

Suanzaoren decoction, as one of the traditional Chinese medicine prescriptions, has been most commonly used in Asian countries and reported to inhibit the process of immunodeficiency insomnia. Polysaccharide is important component which also contributes to the role of immunoprotective and sedative hypnotic effects. This study was aimed to explore the immunoprotective and sedative hypnotic mechanisms of polysaccharide from Suanzaoren decoction by serum metabonomics approach. With this purpose, complex physical and chemical immunodeficiency insomnia models were firstly established according to its multi-target property. Serum samples were analyzed using UHPLC/Q-TOF-MS spectrometry approach to determine endogenous metabolites. Then, principal component analysis was used to distinguish the groups, and partial least squares discriminate analysis was carried out to confirm the important variables. The serum metabolic profiling was identified and pathway analysis was performed after the total polysaccharide administration. The twenty-one potential biomarkers were screened, and the levels were all reversed to different degrees in the total polysaccharide treated groups. These potential biomarkers were mainly related to vitamin, sphingolipid, bile acid, phospholipid and acylcarnitine metabolisms. The result has indicated that total polysaccharide could inhibit insomnia triggered by immunodeficiency stimulation through regulating those metabolic pathways. This study provides a useful approach for exploring the mechanism and evaluating the efficacy of total polysaccharide from Suanzaoren decoction. Copyright © 2018 Elsevier B.V. All rights reserved.

Severe excessive daytime sleepiness induced by hydroxyurea.

PubMed

Revol, Bruno; Joyeux-Faure, Marie; Albahary, Marie-Victoire; Gressin, Remy; Mallaret, Michel; Pepin, Jean-Louis; Launois, Sandrine H

2017-06-01

Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Discriminative stimulus properties of intragastrically administered d-amphetamine and pentobarbital in rhesus monkeys.

PubMed

de la Garza, R; Johanson, C E

1987-12-01

Rhesus monkeys were trained to discriminate intragastrically administered d-amphetamine (AMPH) or pentobarbital (PENTO) from saline using a signaled shock-avoidance trail procedure. All monkeys maintained criterion levels (greater than 90% drug-appropriate responding) throughout the duration of the study during training sessions. In the AMPH experiment, the anorectics diethylpropion, mazindol, phendimetrazine, phenmetrazine and phentermine completely substituted for the training dose of AMPH. The atypical antidepressant bupropion and the psychomotor stimulant methylphenidate also completely substituted for AMPH. Other anorectics including benzphetamine, clortermine, fenetylline, mefenorex and the psychomotor stimulant pemoline that share some pharmacological properties with AMPH substituted for AMPH in some, but not all, of the monkeys tested. The anorectics fenfluramine and chlorphentermine failed to substitute for AMPH. Drugs from other pharmacological classes such as morphine, diazepam, nortripyline and PENTO also failed to substitute for AMPH, indicating pharmacological specificity. In the PENTO experiment, the benzodiazepines alprazolam, bromazepam, diazepam, flurazepam, halazepam, lorazepam, midazolam, oxazepam, temazepam and triazolam and the sedatives methaqualone and phenobarbital completely substituted for the training dose of PENTO. The nonbenzodiazepine anxiolytic CL 218,872 only partially substituted for PENTO. In addition, morphine and AMPH failed to substitute for PENTO, indicating pharmacological specificity. In summary, drugs delivered intragastrically functioned as discriminative stimuli in a drug-class specific manner. The ability to use drugs delivered by this route as discriminative stimuli provides a way to compare anorectic drugs to AMPH or sedative drugs to PENTO under conditions that resemble the mode of human consumption to determine whether these drugs are likely to be associated with AMPH-like or PENTO-like drug dependence.

Topiramate-Induced Somnambulism in a Migraineur: A Probable Idiosyncratic Adverse Effect

PubMed Central

Mathew, Thomas; Sarma, G. R. K.; Nadig, Raghunandan; Varghese, Raji

2012-01-01

Somnambulism (sleepwalking) is a disorder of arousal that falls under “parasomnia” group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers.1 This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine. Citation: Mathew T; Sarma GRK; Nadig R; Varghese R. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect. J Clin Sleep Med 2012;8(2):197-198. PMID:22505867

Hypnotic induction in dentistry--coping with the fear of losing control (autonomy): a brief communication.

PubMed

Kleinhauz, M; Eli, I

1991-07-01

A common cause of stress among dental patients is the patient's fear of losing control in face of the "helplessness provoking" dental situation. Although hypno-relaxation and hypnosis serve as efficient tools to aid in the administration of dental treatment to such patients, some of them may view hypnosis as a further relinquishing of control to the hypnotist and thus resist hypnotic induction, despite their willingness to try to use hypnosis for therapeutic reasons. To avoid this resistance, a "self-control" induction method is suggested that enables the patient to remain in control throughout the process. This technique minimizes the threat of losing one's autonomy and thus enables treatment of these patients.

AZD-3043: A Novel, Metabolically-Labile Sedative/Hypnotic Agent with Rapid and Predictable Emergence from Hypnosis

PubMed Central

Egan, Talmage D.; Obara, Shinju; Jenkins, Thomas E.; Jaw-Tsai, Sarah S.; Amagasu, Shanti; Cook, Daniel R.; Steffensen, Scott C.; Beattie, David T.

2013-01-01

Background Propofol can be associated with delayed awakening after prolonged infusion. The aim of this study was to characterize the preclinical pharmacology of AZD-3043, a positive allosteric modulator of the γ-aminobutyric acidA (GABAA) receptor containing a metabolically-labile ester moiety. We postulated that its metabolic pathway would result in a short acting clinical profile. Methods The effects of AZD-3043, propofol and propanidid were studied on GABAA receptor-mediated chloride currents in embryonic rat cortical neurons. Radioligand binding studies were also performed. The in vitro stability of AZD-3043 in whole blood and liver microsomes was evaluated. The duration of the loss of righting reflex and effects on the electroencephalograph evoked by bolus or infusion intravenous (IV) administration were assessed in rats. A mixed-effects kinetic-dynamic model using minipigs permitted exploration of the clinical pharmacology of AZD-3043. Results AZD-3043 potentiated GABAA receptor-mediated chloride currents and inhibited [35S]tert-butylbicyclophosphorothionate binding to GABAA receptors. AZD-3043 was rapidly hydrolyzed in liver microsomes from humans and animals. AZD-3043 produced hypnosis and electroencephalograph depression in rats. Compared to propofol, AZD-3043 was shorter acting in rats and pigs. Computer simulation using the porcine kinetic-dynamic model demonstrated that AZD-3043 has very short 50 and 80% decrement times independent of infusion duration. Conclusions AZD-3043 is a positive allosteric modulator of the GABAA receptor in vitro and a sedative/hypnotic agent in vivo. The esterase dependent metabolic pathway results in rapid clearance and short duration of action even for long infusions. AZD-3043 may have clinical potential as a sedative/hypnotic agent with rapid and predictable recovery. PMID:22531340

Zolpidem-induced amnesia and somnambulism: rare occurrences?

PubMed

Tsai, Jui-Hsiu; Yang, Pinchen; Chen, Cheng-Chung; Chung, Weilum; Tang, Tze-Chun; Wang, Shing-Yaw; Liu, Jong-Kang

2009-01-01

Zolpidem, a non-benzodiazepine hypnotic of the imidazopyridine class, is very effective in treating insomnia with previous claims of little adverse effects. However, zolpidem-induced somnambulism and amnesic sleep-related behavioral problems were begun to be reported in literature but no systemic investigation has been undertaken in non-Western cultures. In our current retrospective survey, 5.1% (13 out of 255) of Taiwanese patients reported change in sleep-related behavior as adverse effects. This serves as a reminder for clinicians to inquire regarding any unusual behavior of parasomniac activities when prescribing zolpidem.

Hypnotic treatment of PTSD in children who have complicated bereavement.

PubMed

Iglesias, Alex; Iglesias, Adam

Although conceptualized as a normal reaction to loss and not classified as a mental disorder, grief can be considered a focus of treatment. When grief complicates and becomes pathological by virtue of its duration, intensity, and absence or by bizarre or somatic manifestation, a psychiatric diagnosis is in order. Childhood PTSD in Complicated Bereavement is a condition derived from the loss of a loved one when the nature of death is occasioned through traumatic means. The traumatic nature of the loss engenders trauma symptoms, which impinge on the child's normal grieving process and his/ her ability to negotiate the normal grieving system. The 2 cases presented herein constitute single session treatment with clinical hypnosis of PTSD, a result of the traumatic loss of the paternal figures. The setting in which these cases took place was rural Guatemala. Treatment consisted of single session hypnosis with the Hypnotic Trauma Narrative, a tool designed to address the symptomatology of PTSD. Follow-up a week later and telephone follow-up 2 months later demonstrated the resolution of traumatic manifestations and the spontaneous beginning of the normal grief process.

Obsessive-compulsive personality disorder features and response to behavioral therapy for insomnia among patients with hypnotic-dependent insomnia.

PubMed

Petrov, Megan E; Emert, Sarah E; Lichstein, Kenneth L

2018-06-05

To compare therapeutic response to behavioral therapy for insomnia (BT-I) among hypnotic-dependent insomnia (HDI) patients with and without Cluster C personality disorders. Twenty-three adults with HDI (17 females), aged between 33 and 68 (M = 53; SD = 9.9) were included in the study. Participants completed a personality disorder assessment (baseline), as well as sleep diaries, polysomnography (PSG), and an insomnia severity assessment (baseline, posttreatment, and one-year follow-up). Treatment consisted of eight weeks of individual BT-I and gradual hypnotic medication withdrawal. Multilevel mixed-effects linear regression models examined the interaction between study visit and Cluster C personality disorders status on treatment response to BT-I. Obsessive-compulsive personality disorder (OCPD) was the most prevalent of the Cluster C personality disorders with 38% (n = 8) of participants meeting criteria. There were no significant treatment differences by OCPD status across time as measured by sleep diaries and insomnia severity status. However, there were significant treatment differences by OCPD status by one-year follow-up on PSG outcomes, indicating that patients with OCPD status had shorter and more disrupted sleep than patients without OCPD status. Based on self-reported sleep measures, patients with insomnia and features of OCPD responded equivalently to BT-I at one-year follow-up compared to patients without features of OCPD. However, polysomnography outcomes indicated objective sleep deteriorated in these patients, which may suggest greater vulnerability to relapse.

Antidepressants, anxiolytics, and hypnotics in pregnancy and lactation

PubMed Central

Ram, Daya; Gandotra, S.

2015-01-01

Aims: Untreated perinatal depression and anxiety disorders are known to have significant negative impact on both maternal and fetal health. Dilemmas still remain regarding the use and safety of psychotropics in pregnant and lactating women suffering from perinatal depression and anxiety disorders. The aim of the current paper was to review the existing evidence base on the exposure and consequences of antidepressants, anxiolytics, and hypnotics in women during pregnancy and lactation and to make recommendations for clinical decision making in management of these cases. Materials and Methods: We undertook a bibliographic search of Medline/PubMed (1972 through 2014), Science Direct (1972 through 2014), Archives of Indian Journal of Psychiatry databases was done. References of retrieved articles, reference books, and dedicated websites were also checked. Results and Conclusions: The existing evidence base is extensive in studying multiple outcomes of the antidepressant or anxiolytic exposure in neonates, and some of the findings appear conflicting. Selective serotonin reuptake inhibitors are the most researched antidepressants in pregnancy and lactation. The available literature is criticized mostly on the lack of rigorous well designed controlled studies as well as lacunae in the methodologies, interpretation of statistical information, knowledge transfer, and translation of information. Research in this area in the Indian context is strikingly scarce. Appropriate risk-benefit analysis of untreated mental illness versus medication exposure, tailor-made to each patient's past response and preference within in the context of the available evidence should guide clinical decision making. PMID:26330654

Monaural and binaural response properties of neurons in the inferior colliculus of the rabbit: effects of sodium pentobarbital.

PubMed

Kuwada, S; Batra, R; Stanford, T R

1989-02-01

1. We studied the effects of sodium pentobarbital on 22 neurons in the inferior colliculus (IC) of the rabbit. We recorded changes in the sensitivity of these neurons to monaural stimulation and to ongoing interaural time differences (ITDs). Monaural stimuli were tone bursts at or near the neuron's best frequency. The ITD was varied by delivering tones that differed by 1 Hz to the two ears, resulting in a 1-Hz binaural beat. 2. We assessed a neuron's ITD sensitivity by calculating three measures from the responses to binaural beats: composite delay, characteristic delay (CD), and characteristic phase (CP). To obtain the composite delay, we first derived period histograms by averaging, showing the response at each stimulating frequency over one period of the beat frequency. Second, the period histograms were replotted as a function of their equivalent interaural delay and then averaged together to yield the composite delay curve. Last, we calculated the composite peak or trough delay by fitting a parabola to the peak or trough of this composite curve. The composite delay curve represents the average response to all frequencies within the neuron's responsive range, and the peak reflects the interaural delay that produces the maximum response. The CD and CP were estimated from a weighted fit of a regression line to the plot of the mean interaural phase of the response versus the stimulating frequency. The slope and phase intercept of this regression line yielded estimates of CD and CP, respectively. These two quantities are thought to reflect the mechanism of ITD sensitivity, which involves the convergence of phase-locked inputs on a binaural cell. The CD estimates the difference in the time required for the two inputs to travel from either ear to this cell, whereas the CP reflects the interaural phase difference of the inputs at this cell. 3. Injections of sodium pentobarbital at subsurgical dosages (less than 25 mg/kg) almost invariably altered the neuron's response

Integrating the Forensic Sciences in Wildlife Case Investigations: A Case Report of Pentobarbital and Phenytoin Toxicosis in a Bald Eagle (Haliaeetus leucocephalus).

PubMed

Viner, T C; Hamlin, B C; McClure, P J; Yates, B C

2016-09-01

The application of medical knowledge to the purpose of law is the foundation of forensic pathology. A forensic postmortem examination often involves the expertise of multiple scientific disciplines to reconstruct the full story surrounding the death of an animal. Wildlife poses additional challenges in forensic investigations due to little or no associated history, and the disruptive effects of decomposition. To illustrate the multidisciplinary nature of wildlife forensic medicine, the authors outline a case of secondary pentobarbital/phenytoin toxicosis in a bald eagle (Haliaeetus leucocephalus). The eagle was the single fatality in a group of 8 birds that fed on euthanized domestic cat remains that had been improperly disposed of in a landfill. Cooperation between responding law enforcement officers, pathologists, and other forensic scientists led to the successful diagnosis and resolution of the case. © The Author(s) 2016.

Drug-induced apnea.

PubMed

Boutroy, M J

1994-01-01

Drugs have been in the past and will in the future still be liable to induce apnea in neonates, infants and older children. At these different stages of development, the child may be abnormally vulnerable to respiratory disorders and apnea, and doses of drugs, without any abnormal side effects in adult patients, can be harmful in younger subjects. Drugs responsible for apnea during development are numerous, but more than half of the problems are induced by sedatives and hypnotics, among which phenothiazines, barbiturates, benzodiazepines (included transplacentally acquired) and general anesthetics are a few. Other pharmacological families are apnea inducers in the neonatal period and childhood: analgesics and opioid narcotics, agents acting at the levels of neuromuscular function and autonomic ganglia, and cardiovascular agents. The pathogenesis of these apneas depends on the disturbance of any mechanism responsible for the respiratory activity: medullary centers and brain stem structures, afferent influx to CNS, sleep stages, upper airways, lungs and respiratory muscles. At key stages such as birth and infancy, drugs may emphasize the particular sensitivity of the mechanisms responsible for inducing apnea. This might explain unexpected respiratory disorders during development.

Polysomnographic evaluation of the hypnotic effect of Valeriana edulis standardized extract in patients suffering from insomnia.

PubMed

Herrera-Arellano, A; Luna-Villegas, G; Cuevas-Uriostegui, M L; Alvarez, L; Vargas-Pineda, G; Zamilpa-Alvarez, A; Tortoriello, J

2001-11-01

Valeriana edulis ssp. procera, commonly known as "valeriana mexicana", is widely used in Mexican traditional medicine for the treatment of insomnia and anxiety. To evaluate the hypnotic effect and safety of 450 mg of Valeriana edulis standardized hydroalcoholic extract in patients with insomnia, a double-blind, cross-over, controlled study was carried out. Valeriana officinalis extract, at the same doses, was used as a positive control. In a sleep laboratory, polysomnographic (PSG) recordings were performed for analyzing the quantity and architecture of sleep as well as evaluating morning sleepiness, memory quotient, and side effects. The experimental procedures were conducted on four consecutive nights of 8 h each. Twenty patients were admitted. Based on the PSG results, V. edulis reduced the number of awaking episodes while both treatments increased the rapid eye movement (REM) sleep; this last parameter was better improved by V. officinalis extract. Other PSG data did not achieve outstanding statistical differences, but the clinical tendency with both treatments was to increase the sleep efficiency index. These Valeriana extracts produced beneficial effects on sleep architecture because they diminished the time of stages 1 and 2 in non-REM sleep while they increased delta sleep. Validated clinical tests showed that both species reduced notoriously the morning sleepiness, that was further improved by V. officinalis extract, and did not affect anterograde memory. In only three cases were slight side effects observed, one due to the experimental extract. Chemical analysis of the hydroalcoholic extract of V. edulis indicated that this extract contains 0.26 % of dihydroisovaltrate as the main valepotriate, and that it does not contain valerenic acid. In general, the results support the hypnotic effect and safety of acute treatment of Valeriana edulis and Valeriana officinalis on patients suffering insomnia.

Barbiturate euthanasia solution-induced tissue artifact in nonhuman primates.

PubMed

Grieves, J L; Dick, E J; Schlabritz-Loutsevich, N E; Butler, S D; Leland, M M; Price, S E; Schmidt, C R; Nathanielsz, P W; Hubbard, G B

2008-06-01

Barbiturate euthanasia solutions are a humane and approved means of euthanasia. Overdosing causes significant tissue damage in a variety of laboratory animals. One hundred seventeen non-human primates (NHP) representing 7 species including 12 fetuses euthanized for humane and research reasons by various vascular routes with Euthasol, Sodium Pentobarbital, Fatal Plus, Beuthanasia D, or Euthanasia 5 were evaluated for euthanasia-induced tissue damage. Lungs and livers were histologically graded for hemolysis, vascular damage, edema, and necrosis. Severity of tissue damage was analyzed for differences on the basis of agent, age, sex, dose, and injection route. Severity of tissue damage was directly related to dose and the intracardiac injection route, but did not differ by species, sex, and agent used. When the recommended dose of agent was used, tissue damage was generally reduced, minimal, or undetectable. Barbiturate-induced artifacts in NHPs are essentially the same as in other laboratory species.

Suggestion-Induced Modulation of Semantic Priming during Functional Magnetic Resonance Imaging

PubMed Central

Ulrich, Martin; Kiefer, Markus; Bongartz, Walter; Grön, Georg; Hoenig, Klaus

2015-01-01

Using functional magnetic resonance imaging during a primed visual lexical decision task, we investigated the neural and functional mechanisms underlying modulations of semantic word processing through hypnotic suggestions aimed at altering lexical processing of primes. The priming task was to discriminate between target words and pseudowords presented 200 ms after the prime word which was semantically related or unrelated to the target. In a counterbalanced study design, each participant performed the task once at normal wakefulness and once after the administration of hypnotic suggestions to perceive the prime as a meaningless symbol of a foreign language. Neural correlates of priming were defined as significantly lower activations upon semantically related compared to unrelated trials. We found significant suggestive treatment-induced reductions in neural priming, albeit irrespective of the degree of suggestibility. Neural priming was attenuated upon suggestive treatment compared with normal wakefulness in brain regions supporting automatic (fusiform gyrus) and controlled semantic processing (superior and middle temporal gyri, pre- and postcentral gyri, and supplementary motor area). Hence, suggestions reduced semantic word processing by conjointly dampening both automatic and strategic semantic processes. PMID:25923740

Annual Research Report, 1 July 1969 - 30 June 1970.

DTIC Science & Technology

1970-06-30

of irradiated rats to tolerate pentobarbital was measured after treatment with amphetamine and/or reserpine. Male Sprague-Dawley rats were given 250...Reserpine treated (24 h after 1000 rads) 10 91.1 + 5.9 Reserpine and Amphetamine treated (24 h after 1000 rads) 11 84.7 + 2.9 * p ɘ. 05 ( treatment group...tolerance to sodium pentobarbital was observed. Four days of reserpine treatment prior to irradiation also abolished the radiation-induced increase in

Gradual increase in cutaneous threshold induced by repeated hypnosis of healthy individuals and patients with atopic eczema.

PubMed

Hájek, P; Jakoubek, B; Radil, T

1990-04-01

Gradual increase in cutaneous pain threshold was found in healthy subjects and patients with atopic eczema during repeated hypnotic sessions with specific suggestions. This increase was less in the former than in the latter group. Repeated threshold measurements did not influence the threshold. The analgesic effect outlasted the hypnotic sessions by several months. It could be, however, suddenly reduced by appropriate hypnotic suggestion.

Inhibition of cyclooxygenase and nitric oxide synthase in hypoxic vasoconstriction and oleic acid-induced lung injury.

PubMed

Leeman, M; de Beyl, V Z; Biarent, D; Maggiorini, M; Mélot, C; Naeije, R

1999-05-01

Cyclooxygenase (COX) products and nitric oxide (NO) inhibit hypoxic pulmonary vasoconstriction (HPV), and their release could contribute to alterations in gas exchange in lung injury. We tested the hypothesis that combined blockade of COX and NO synthase (NOS) could further increase HPV and better protect gas exchange in lung injury than could blockade of either COX or NOS alone. We determined pulmonary vascular pressure-flow relationships in pentobarbital-anesthetized and ventilated dogs submitted to hypoxic challenges before and after administration of solvent (n = 4), indomethacin alone (2 mg/kg intravenously, n = 8), Nomega-nitro-L-arginine (L-NA) alone (10 mg/kg intravenoulsy, n = 8), indomethacin followed by L-NA (n = 8), and L-NA followed by indomethacin (n = 8). All of the dogs so treated then received oleic acid (0.06 ml/kg intravenously) to induce lung injury. Blood flow was manipulated by establishing a femoral arteriovenous bypass or by inflating an inferior vena caval balloon. Gas exchange was evaluated by measuring arterial PO2 and intrapulmonary shunt (using the inert gas sulfur hexafluoride) at identical cardiac outputs. The magnitude of HPV was not affected by solvent. Indomethacin and L-NA given separately enhanced HPV. L-NA added to indomethacin further enhanced HPV, as did indomethacin added to L-NA. After oleic acid-induced lung injury, gas exchange deteriorated less in dogs pretreated with indomethacin than in dogs pretreated with solvent or with L-NA alone. These results suggest that in pentobarbital-anesthetized dogs: (1) the magnitude of HPV is limited by the corelease of COX metabolites and of NO; and (2) inhibition of COX, but not of NOS, attenuates the deterioration of gas exchange in oleic acid-induced lung injury.

A multicenter study of sleep-wake rhythm disorders: therapeutic effects of vitamin B12, bright light therapy, chronotherapy and hypnotics.

PubMed

Yamadera, H; Takahashi, K; Okawa, M

1996-08-01

One hundred and six subjects with primary sleep-wake rhythm disorders [13 non-24 hour sleep-wake syndrome (non-24), 76 delayed sleep phase syndrome (DSPS), 11 irregular sleep-wake pattern (irregular) and six long sleepers] were treated with vitamin B12, bright light, chronotherapy and/or hypnotics. These therapies caused moderate or remarkable improvement in 32% of the non-24, 42% of DSPS, 45% of irregular and 67% of long sleepers. A lack of adequate sleep, unpleasant feelings at waking and daytime drowsiness were also improved in DSPS.

Opioid, calcium, and adrenergic receptor involvement in protopine analgesia.

PubMed

Xu, Q; Jin, R L; Wu, Y Y

1993-11-01

The analgesic effect of protopine (Pro), an alkaloid isolated from Papaveraceae, was confirmed by tail-pinch and hot-plate tests when given sc 10-40 mg.kg-1, and 20-40 mg.kg-1 inhibited the spontaneous movements of mice. Pro 40 mg.kg-1 increased the sleeping rate, prolonged the sleeping duration, and shortened the sleeping latency in mice hypnotized by ip pentobarbital sodium 30 mg.kg-1. Pro 10-40 mg.kg-1 did not affect the inflammatory reaction induced by xylene and egg white. An icv injection of Pro 20-200 micrograms/mouse showed a remarkable analgesic effect in mice. The icv pretreatment of naloxone 2 micrograms blocked the analgesic effect completely. CaCl2 40 micrograms/mouse (ICV) or methotrexate 10 mg.kg-1 (ip), an agonist of Ca2+ channel, showed a complete blockade of the analgesia, while nifedipine 100 mg.kg-1(po), a blocker of Ca2+ channel, enhanced the analgesic effect. The ip pretreatment of reserpine 4 mg.kg-1 reduced the Pro analgesia. Phentolamine 10 mg.kg-1(ip), an alpha-adrenergic blocker, tended to weaken the analgesia, but propranolol 10 mg.kg-1(ip), a beta-blocker, did not affect it. These results suggest that Pro displays its analgesic effect mainly through the opioid and calcium systems and partly through the adrenergic mechanism.

Saffan induced poikilothermia in cheetah (Acinonyx jubatus).

PubMed

Button, C; Meltzer, D G; Mülders, M S

1981-09-01

The steroidal anaesthetic agent Saffan (a 1,2% m/v mixture of alphaxalone and alphadolone) induced a state of poikilothermia in cheetahs. On a warm day (maximum temperature 29 degrees C) rectal temperatures rose in 7 of 8 male cheetahs given Saffan. The highest rectal temperature recorded was 41 degrees C. On a cool day (minimum temperature 19,5 degrees C) rectal temperature fell in 6 of 6 male cheetahs. The lowest rectal temperatures recorded was 36,2 degrees C. Saffan at 3 mg/kg intravenously in cheetahs is an excellent and safe hypnotic but should be used with caution on both hot and cold days.

Road traffic crash risk associated with benzodiazepine and z‐hypnotic use after implementation of a colour‐graded pictogram: a responsibility study

PubMed Central

Luxcey, Audrey; Contrand, Benjamin; Gadegbeku, Blandine; Delorme, Bernard; Tricotel, Aurore; Moore, Nicholas; Salmi, Louis‐Rachid; Lagarde, Emmanuel

2016-01-01

Aims To assess potential change in medicine exposure and association with the risk of road traffic crash across a time period that started before the implementation of a grading system warning of the effect of medicine on driving performance. Methods Data from three French national databases were extracted and matched: the national health care insurance database, police reports and the national police database of injurious crashes. Drivers involved in such crashes in France, from July 2005 to December 2011 and identified by their national identifier, were included. Association with the risk of crash was estimated using a case–control analysis comparing benzodiazepine and z‐hypnotic use among drivers responsible or not responsible for the crash. Results Totals of 69 353 responsible and 73 410 non‐responsible drivers involved in an injurious crash were included. Exposure to benzodiazepine anxiolytics was associated with an increased risk of being responsible for a road traffic crash during the pre‐intervention period (OR = 1.42 [1.24–1.62]). The association disappeared in the post‐intervention period, but became significant again thereafter. The risk of being responsible for a crash increased in users of z‐hypnotics across the study period. Conclusions Our results question the efficacy of the measures implemented to promote awareness about the effects of medicines on driving abilities. Prevention policies relating to the general driving population, but also to healthcare professionals, should be reviewed. PMID:27544927

Increased Prevalence of Insomnia and Changes in Hypnotics Use in England over 15 Years: Analysis of the 1993, 2000, and 2007 National Psychiatric Morbidity Surveys

PubMed Central

Calem, Maria; Bisla, Jatinder; Begum, Aysha; Dewey, Michael; Bebbington, Paul E.; Brugha, Traolach; Cooper, Claudia; Jenkins, Rachel; Lindesay, James; McManus, Sally; Meltzer, Howard; Spiers, Nicola; Weich, Scott; Stewart, Robert

2012-01-01

Study Objectives: To investigate changes over 15 years in the prevalence of insomnia and its association with demographic characteristics and hypnotic medication use. Design: Analysis of 3 cross-sectional national mental health surveys carried out in 1993, 2000, and 2007, which used comparable sampling methods and identical insomnia assessments. Setting: Adults living in private households in England. Patients or Participants: 20,503 people aged 16-64 years. Measurements and Results: Insomnia was defined according to 4 different criteria, using relevant questions from the revised Clinical Interview Schedule. Modest increases in insomnia prevalence were found over the survey periods (any symptoms increasing from 35.0% in 1993 to 38.6% in 2007; insomnia diagnosis from 3.1% to 5.8%, respectively). In all 3 surveys, similar strengths of association in relation to all criteria were found, with female gender, increased age, lower educational attainment, depression, unemployment, economic inactivity, and widowed, divorced, or separated status. Prevalence of hypnotic use was double in 2000 (0.8%) compared to 1993 (0.4%); from limited information on selected medications, there was no such increase between 2000 and 2007. The reasons reported for any sleep disturbance over the last month were generally similar across surveys, the most marked change being illness/discomfort increasing as an explanation from 14.3% to 17.4% to 19.0%. Conclusions: In the English general population, insomnia (by any definition) showed a modest but steady increase in prevalence over a 15-year period. Strengths of associations with demographic factors and self-reported reasons for sleep disturbance remained reasonably stable over this period. Citation: Calem M; Bisla J; Begum A; Dewey M; Bebbington PE; Brugha T; Cooper C; Jenkins R; Lindesay J; McManus S; Meltzer H; Spiers N; Weich S; Stewart R. Increased prevalence of insomnia and changes in hypnotics use in England over 15 years: analysis of the

Adjunctive Self-hypnotic Relaxation for Outpatient Medical Procedures: A Prospective Randomized Trial with Women Undergoing Large Core Breast Biopsy

PubMed Central

Lang, Elvira V.; Berbaum, Kevin S.; Faintuch, Salomao; Hatsiopoulou, Olga; Halsey, Noami; Li, Xinyu; Berbaum, Michael L.; Laser, Eleanor; Baum, Janet

2008-01-01

Medical procedures in outpatient settings have limited options of managing pain and anxiety pharmacologically. We therefore assessed whether this can be achieved by adjunct self-hypnotic relaxation in a common and particularly anxiety provoking procedure. 236 women referred for large core needle breast biopsy to an urban tertiary university-affiliated medical center were prospectively randomized to receive standard care (n=76), structured empathic attention (n= 82), or self-hypnotic relaxation (n=78) during their procedures. Patients’ self-ratings at 10 minute-intervals of pain and anxiety on 0–10 verbal analog scales with 0=no pain/anxiety at all, 10=worst pain/anxiety possible, were compared in an ordinal logistic regression model. Women’s anxiety increased significantly in the standard group (logit slope = 0.18, p < 0.001), did not change in the empathy group (slope = −0.04, p = 0.45), and decreased significantly in the hypnosis group (slope = −0.27, p < 0.001). Pain increased significantly in all three groups (logit slopes: standard care = 0.53, empathy = 0.37, hypnosis = 0.34; all p < 0.001) though less steeply with hypnosis and empathy than standard care (p = 0.024 and p = 0.018 respectively). Room time and cost were not significantly different in an univariate ANOVA despite hypnosis and empathy requiring an additional professional: 46 minutes/$161 for standard care, 43 minutes/$163 for empathy, and 39 minutes/$152 for hypnosis. We conclude that, while both structured empathy and hypnosis decrease procedural pain and anxiety, hypnosis provides more powerful anxiety relief without undue cost and thus appears attractive for outpatient pain management. PMID:16959427

Polygonatum sibiricum rhizome promotes sleep by regulating non-rapid eye movement and GABAergic/serotonergic receptors in rodent models.

PubMed

Jo, Kyungae; Suh, Hyung Joo; Choi, Hyeon-Son

2018-05-29

The aim of this study is to investigate the sleep-promoting effect of a water extract of the Polygonatum sibiricum rhizome (PSE) in rodent models. PSE contained oleamide (0.10 mg/g extract) and glyceryl monolinoleate (0.17 mg/g extract), which are recognized as sleep-promoting substances. In pentobarbital-induced sleep model at hypnotic level, PSE (160 mg/kg) administration significantly decreased sleep latency time by 29% (2.7 min) and increased sleep duration time by 70% (68.4 min) compared with the normal control (3.8 min and 40.7 min, respectively). In the electroencephalography (EEG) analysis of rats, PSE-mediated sleep promotion accompanied the change of sleep architecture including increase of non-rapid eye movement (NREM) and decrease of REM. This sleep promoting effect was more obvious in caffeine-induced awakening model; total sleep time was increased by 40% along with increased NREM by PSE treatment at 160 mg/kg. In addition, PSE significantly increased the protein and mRNA levels of GABA A -R2 and 5-HT1A receptor, the major sleep-related neurotransmitter receptors. Furthermore, glyceryl monolinoleate and oleamide effectively bound to GABA A receptor in a competitive binding assay. These results indicate that PSE-mediated sleep-promoting effect is associated with the extension of NREM and upregulation of GABA A -R2 and 5-HT1A, and is mediated by binding to the GABA A receptor in vertebrate models. Copyright © 2018. Published by Elsevier Masson SAS.

Role of Interleukin-1 Receptor Signaling in the Behavioral Effects of Ethanol and Benzodiazepines

PubMed Central

Blednov, Yuri A.; Benavidez, Jillian M.; Black, Mendy; Mayfield, Jody; Harris, R. Adron

2015-01-01

Gene expression studies identified the interleukin-1 receptor type I (IL-1R1) as part of a pathway associated with a genetic predisposition to high alcohol consumption, and lack of the endogenous IL-1 receptor antagonist (IL-1ra) strongly reduced ethanol intake in mice. Here, we compared ethanol-mediated behaviors in mice lacking Il1rn or Il1r1. Deletion of Il1rn (the gene encoding IL-1ra) increases sensitivity to the sedative/hypnotic effects of ethanol and flurazepam and reduces severity of acute ethanol withdrawal. Conversely, deletion of Il1r1 (the gene encoding the IL-1 receptor type I, IL-1R1) reduces sensitivity to the sedative effects of ethanol and flurazepam and increases the severity of acute ethanol withdrawal. The sedative effects of ketamine and pentobarbital were not altered in the knockout (KO) strains. Ethanol intake and preference were not changed in mice lacking Il1r1 in three different tests of ethanol consumption. Recovery from ethanol-induced motor incoordination was only altered in female mice lacking Il1r1. Mice lacking Il1rn (but not Il1r1) showed increased ethanol clearance and decreased ethanol-induced conditioned taste aversion. The increased ethanol- and flurazepam-induced sedation in Il1rn KO mice was decreased by administration of IL-1ra (Kineret), and pre-treatment with Kineret also restored the severity of acute ethanol withdrawal. Ethanol-induced sedation and withdrawal severity were changed in opposite directions in the null mutants, indicating that these responses are likely regulated by IL-1R1 signaling, whereas ethanol intake and preference do not appear to be solely regulated by this pathway. PMID:25839897

Role of interleukin-1 receptor signaling in the behavioral effects of ethanol and benzodiazepines.

PubMed

Blednov, Yuri A; Benavidez, Jillian M; Black, Mendy; Mayfield, Jody; Harris, R Adron

2015-08-01

Gene expression studies identified the interleukin-1 receptor type I (IL-1R1) as part of a pathway associated with a genetic predisposition to high alcohol consumption, and lack of the endogenous IL-1 receptor antagonist (IL-1ra) strongly reduced ethanol intake in mice. Here, we compared ethanol-mediated behaviors in mice lacking Il1rn or Il1r1. Deletion of Il1rn (the gene encoding IL-1ra) increases sensitivity to the sedative/hypnotic effects of ethanol and flurazepam and reduces severity of acute ethanol withdrawal. Conversely, deletion of Il1r1 (the gene encoding the IL-1 receptor type I, IL-1R1) reduces sensitivity to the sedative effects of ethanol and flurazepam and increases the severity of acute ethanol withdrawal. The sedative effects of ketamine and pentobarbital were not altered in the knockout (KO) strains. Ethanol intake and preference were not changed in mice lacking Il1r1 in three different tests of ethanol consumption. Recovery from ethanol-induced motor incoordination was only altered in female mice lacking Il1r1. Mice lacking Il1rn (but not Il1r1) showed increased ethanol clearance and decreased ethanol-induced conditioned taste aversion. The increased ethanol- and flurazepam-induced sedation in Il1rn KO mice was decreased by administration of IL-1ra (Kineret), and pre-treatment with Kineret also restored the severity of acute ethanol withdrawal. Ethanol-induced sedation and withdrawal severity were changed in opposite directions in the null mutants, indicating that these responses are likely regulated by IL-1R1 signaling, whereas ethanol intake and preference do not appear to be solely regulated by this pathway. Copyright © 2015 Elsevier Ltd. All rights reserved.

Occurrence and fate of barbiturates in the aquatic environment.

PubMed

Peschka, Manuela; Eubeler, Jan P; Knepper, Thomas P

2006-12-01

Barbiturates have been widely used as sedative hypnotics in the mid-1960s and since then mainly as veterinary drugs. To monitor their presence and fate in the aquatic environment, a method based on gas chromatography-mass spectrometry (GC-MS) has been developed to quantify butalbital, secobarbital, hexobarbital, aprobarbital, phenobarbital, and pentobarbital, all with a limit of detection (LOD) down to 1 ng/L. From the various investigated waste and surface water samples, barbiturates were only, but regularly detected in the Mulde, a tributary of the river Elbe in Germany at relevant concentrations up to several microg/L. Investigations of groundwater being affected with wastewater infiltration several decades ago also revealed a barbiturate pattern, indicating a strong recalcitrance of these drugs. To confirm this hypothesis, studies were carried out on biotic and abiotic degradation. Both, the biodegradability under aerobic conditions and hydrolysis did not show any degradation, implementing, that the investigated barbiturates, once released into the aquatic environment, show high stability over a long period of time.

Hypnotics and driving safety: meta-analyses of randomized controlled trials applying the on-the-road driving test.

PubMed

Verster, Joris C; Veldhuijzen, Dieuwke S; Patat, Alain; Olivier, Berend; Volkerts, Edmund R

2006-01-01

Many people who use hypnotics are outpatients and are likely to drive a car the day after drug intake. The purpose of these meta-analyses was to determine whether or not this is safe. Placebo-controlled, randomized, double-blind trials were selected if using the on-the-road driving test to determine driving ability the day following one or two nights of treatment administration. Primary outcome measure of the driving test was the Standard Deviation of Lateral Position (SDLP); i.e., the weaving of the car. Fixed effects model meta-analyses were performed. Effect size (ES) was computed using mean standardized (weighted) difference scores between treatment and corresponding placebo SDLP values. Ten studies, published from 1984 to 2002 (207 subjects), were included in the meta-analyses. The morning following bedtime administration, i.e. 10-11 hours after dosing, significant driving impairment was found for the recommended dose of various benzodiazepine hypnotics (ES=0.42; 95% Confidence Interval (CI)=0.14 to 0.71). Twice the recommended dose impaired driving both in the morning (ES=0.68; CI=0.39 to 0.97) and afternoon, i.e. 16-17 hours after dosing (ES=0.57; CI=0.26 to 0.88). Zopiclone 7.5 mg also impaired driving in the morning (ES=0.89; CI=0.54 to 1.23). Zaleplon (10 and 20 mg) and zolpidem (10 mg) did not affect driving performance the morning after dosing. Following middle-of-the-night administration, significantly impaired driving performance was found for zopiclone 7.5 mg (ES=1.51, CI=0.85 to 2.17), zolpidem 10 mg (ES=0.66, CI=0.13 to 1.19) and zolpidem 20 mg (ES=1.16, CI=0.60 to 1.72). Zaleplon (10 and 20 mg) did not affect driving performance. The analyses show that driving a car the morning following nocturnal treatment with benzodiazepines and zopiclone is unsafe, whereas the recommended dose of zolpidem (10 mg) and zaleplon (10 mg) do not affect driving ability.

Zaleplon-induced Anemsic Somnambulism with Eating Behaviors Under Once Dose.

PubMed

Chen, Yen-Wen; Tseng, Ping-Tao; Wu, Ching-Kuan; Chen, Chien-Chih

2014-12-01

Zaleplon is a newly-developed rapid-acting non-benzodiazepine hypnotic. Few reports discuss zaleplon-induced somnambulism. This report describes a patient without history of somnambulism, who developed amnesic somnambulism after taking low-dose of zaleplon. A 43-year-old schizophrenic male without history of physical illness, seizure, or somnambulism developed amnesic somnambulism after taking once low-dose of zaleplon from the outpatient-department. Somnambulism did not reoccur after discontinuing zaleplon. However, similar behaviors recurred after accidentally prescribing zaleplon on the first-day of hospitalization. This patient is the first case without history of somnambulism, who developed zaleploninduced somnambulism after taking low-dose of zaleplon. This study underscores the importance of monitoring for zaleplon-induced somnambulism, even when administering low-dosage to those without risk factors or history of somnambulism.

[Gazing into the depths of the soul: hypnotism in documentary and instructional film (1920-1936)].

PubMed

Ledebur, Sophie

2014-12-01

Although part of the medical fold since the 1870s, hypnosis was long relegated to the margins, recognised and used by only a relatively small group of medical professionals. In the decades around 1900 hypnotic techniques were monopolised as a form of medical treatment through a long and in no way linear process. Hypnosis of laymen was vehemently opposed, however, denounced as being far too dangerous. And yet, medical participation in the aura of spectacular intervention into the human psyche garnered support. The medium of both documentary and instructional film served an important function in this regard, conveying popular interest in acknowledging hypnosis as a scientific method. On the basis of four medically accredited films on hypnosis from 1920 to 1936, this paper attempts to investigate how medical experts and these genres, as part of their effort to claim hypnosis from the realm of public spectacle and parapsychological experimentation, worked to stabilise hypnosis as a purified form of medical and psychiatric practice.

A conveyor belt task for assessing visuo-motor coordination in the marmoset (Callithrix jacchus): effects of diazepam, chlorpromazine, pentobarbital and d-amphetamine.

PubMed

D'Mello, G D; Duffy, E A; Miles, S S

1985-01-01

A conveyor belt task for assessing visuo-motor coordination in the marmoset is described. Animals are motivated by apple, a preferred food, under a state of minimal food deprivation. The apparatus used was designed to test animals within their home cages and not restrained in any way, thus avoiding possible confounding factors associated with restraint stress. Stable baseline levels of performance were reached by all animals in a median of 24 sessions. Performance was shown to be differentially sensitive to the effects of four psychoactive drugs. Moderate doses of diazepam, chlorpromazine and pentobarbital disrupted visuo-motor coordination in a dose-related manner. The possibility that disruption of performance observed at higher doses may have resulted from non-specific actions of these drugs such as decreases in feeding motivation were not supported by results from ancillary experiments. Changes in performance characteristic of high dose effects were similar in nature to changes observed when the degree of task difficulty was increased. Doses of d-amphetamine up to and including those reported to produce signs of stereotypy failed to influence performance. The potential of the conveyor belt task for measuring visuo-motor coordination in both primate and rodent species is discussed.

Anesthetic effects of a combination of medetomidine, midazolam and butorphanol on the production of offspring in Japanese field vole, Microtus montebelli.

PubMed

Kageyama, Atsuko; Tohei, Atsushi; Ushijima, Hitoshi; Okada, Konosuke

2016-09-01

Pentobarbital sodium (Somnopentyl) can induce surgical anesthesia with a strong hypnotic effect that causes loss of consciousness. Animals have been known to die during experimental surgery under anesthesia with Somnopentyl, causing it to be declared inadequate as a general anesthetic for single treatment. An anesthetic combination of 0.3 mg/kg medetomidine, 4.0 mg/kg midazolam and 5.0 mg/kg butorphanol (M/M/B:0.3/4/5) was reported to induce anesthesia for a duration of around 40 min in ICR mice; similar anesthetic effects were reported in both male and female BALB/c and C57BL/6J strains of mice. However, the anesthetic effects of this combination in Japanese field vole, Microtus montebelli, remain to be evaluated. In the present study, we assessed the effects of Somnopentyl and different concentrations of anesthetic combination (M/M/B:0.3/4/5, 0.23/3/3.75 or 0.15/2/2.5) in Japanese field voles, by means of anesthetic scores. We also examined effect of these anesthetics on production of offspring. Death of the animals was observed only with Somnopentyl. The anesthetic score of Somnopentyl was lower than those of the other anesthetics, although there were no significant differences in duration, body weight and frequency of respiratory among the evaluated anesthetics. Abortion rate with Somnopentyl was significantly higher than that with the M/M/B:0.23/3/3.75 combination, although there was no significant difference in the number of offspring between two. In conclusion, results of this study provide basic information for achieving appropriate anesthetic concentrations in addition to indicating a new, safe and effective surgical anesthetic for Japanese field voles.

Cholinergic aspects of cyanide intoxication

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

Von Bredow, J.D.; Vick, J.A.

1993-05-13

The acute exposure of pentobarbital anesthetized dogs to cyanide leads to a rapid increase and sudden halt in respiration accompanied by cardiovascular irregularities and extreme bradycardia which ultimately lead to cardiac arrest and death. Cardiac irregularities and cardiac arrest in the presence of cyanide induced respiratory arrest are assumed to be due to anoxia and therefore unresponsive to cardiotonic agents. Pretreatment or treatment with atropine sulfate or methyl atropine nitrate provides a marked reduction in the cardiovascular irregularities, bradycardia and hypotension. The cyanide induced cardiovascular effect can also be prevented by bilateral vagotomy. An intramuscularly injected combination of 20 mg/kgmore » sodium nitrite and 1 mg/kg of atropine sulfate ensured recovery of pentobarbital anesthetized dogs exposed to lethal concentrations (2.5 mg/kg i.v.) of sodium cyanide.« less

The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes.

PubMed

Cheng, Xing; Xia, Zhengyuan; Leo, Joyce M; Pang, Catherine C Y

2005-09-05

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

Exposure to benzodiazepines (anxiolytics, hypnotics and related drugs) in seven European electronic healthcare databases: a cross-national descriptive study from the PROTECT-EU Project.

PubMed

Huerta, Consuelo; Abbing-Karahagopian, Victoria; Requena, Gema; Oliva, Belén; Alvarez, Yolanda; Gardarsdottir, Helga; Miret, Montserrat; Schneider, Cornelia; Gil, Miguel; Souverein, Patrick C; De Bruin, Marie L; Slattery, Jim; De Groot, Mark C H; Hesse, Ulrik; Rottenkolber, Marietta; Schmiedl, Sven; Montero, Dolores; Bate, Andrew; Ruigomez, Ana; García-Rodríguez, Luis Alberto; Johansson, Saga; de Vries, Frank; Schlienger, Raymond G; Reynolds, Robert F; Klungel, Olaf H; de Abajo, Francisco José

2016-03-01

Studies on drug utilization usually do not allow direct cross-national comparisons because of differences in the respective applied methods. This study aimed to compare time trends in BZDs prescribing by applying a common protocol and analyses plan in seven European electronic healthcare databases. Crude and standardized prevalence rates of drug prescribing from 2001-2009 were calculated in databases from Spain, United Kingdon (UK), The Netherlands, Germany and Denmark. Prevalence was stratified by age, sex, BZD type [(using ATC codes), i.e. BZD-anxiolytics BZD-hypnotics, BZD-related drugs and clomethiazole], indication and number of prescription. Crude prevalence rates of BZDs prescribing ranged from 570 to 1700 per 10,000 person-years over the study period. Standardization by age and sex did not substantially change the differences. Standardized prevalence rates increased in the Spanish (+13%) and UK databases (+2% and +8%) over the study period, while they decreased in the Dutch databases (-4% and -22%), the German (-12%) and Danish (-26%) database. Prevalence of anxiolytics outweighed that of hypnotics in the Spanish, Dutch and Bavarian databases, but the reverse was shown in the UK and Danish databases. Prevalence rates consistently increased with age and were two-fold higher in women than in men in all databases. A median of 18% of users received 10 or more prescriptions in 2008. Although similar methods were applied, the prevalence of BZD prescribing varied considerably across different populations. Clinical factors related to BZDs and characteristics of the databases may explain these differences. Copyright © 2015 John Wiley & Sons, Ltd.

Using Hypnotic Suggestion to Model Loss of Control and Awareness of Movements: An Exploratory fMRI Study

PubMed Central

Oakley, David A.; Bell, Vaughan; Koppel, Cristina; Mehta, Mitul A.; Halligan, Peter W.

2013-01-01

The feeling of voluntary control and awareness of movement is fundamental to our notions of selfhood and responsibility for actions, yet can be lost in neuropsychiatric syndromes (e.g. delusions of control, non-epileptic seizures) and culturally influenced dissociative states (e.g. attributions of spirit possession). The brain processes involved remain poorly understood. We used suggestion and functional magnetic resonance imaging (fMRI) to investigate loss of control and awareness of right hand movements in 15 highly hypnotically suggestible subjects. Loss of perceived control of movements was associated with reduced connectivity between supplementary motor area (SMA) and motor regions. Reduced awareness of involuntary movements was associated with less activation in parietal cortices (BA 7, BA 40) and insula. Collectively these results suggest that the sense of voluntary control of movement may critically depend on the functional coupling of SMA with motor systems, and provide a potential neural basis for the narrowing of awareness reported in pathological and culturally influenced dissociative phenomena. PMID:24205198

Encapsulation and release of the hypnotic agent zolpidem from biodegradable polymer microparticles containing hydroxypropyl-beta-cyclodextrin.

PubMed

Trapani, Giuseppe; Lopedota, Angela; Boghetich, Giancarlo; Latrofa, Andrea; Franco, Massimo; Sanna, Enrico; Liso, Gaetano

2003-12-11

The goal of this study was to design a prolonged release system of the hypnotic agent zolpidem (ZP) useful for the treatment of insomnia. In this work, ZP alone or in the presence of HP-beta-CD was encapsulated in microparticles constituted by poly(DL-lactide) (PDLLA) and poly(DL-lactide-co-glycolide) (PLGA) and the drug release from these systems was evaluated. ZP alone-loaded microparticles were prepared by the classical O/W emulsion-solvent evaporation method. Conversely, ZP/HP-beta-CD containing microparticles were prepared by the W/O/W emulsion-solvent evaporation method following two different procedures (i.e. A and B). Following procedure A, the previously produced ZP/HP-beta-CD solid complex was added to the water phase of primary emulsion. In the procedure B, HP-beta-CD was added to the aqueous phase and ZP to the organic phase. The resulting microparticles were characterized about morphology, size, encapsulation efficiency and release rates. FT-IR, X-ray, and DSC results suggest the drug is in an essentially amorphous state within the microparticles. The release profiles of ZP from microparticles were in general biphasic, being characterized by an initial burst effect and a subsequent slow ZP release. It resulted that co-encapsulating ZP with or without HP-beta-CD in PDLLA and PLGA the drug release from the corresponding microparticles was protracted. Moreover, in a preliminary pharmacological screening, the ataxic activity in rats was investigated and it was found that intragastric administration of the ZP/HP-beta-CD/PLGA microparticles prepared according to procedure B produced the same ataxic induction time as the one induced by the currently used formulation Stilnox. Interestingly moreover, there was a longer ataxic lasting and a lower intensity of ataxia produced by the ZP/HP-beta-CD/PLGA-B-formulation already after 60 min following the administration. However, a need for further pharmacokinetic and pharmacodynamic studies resulted to fully evaluate

A Comparison of the Efficacy of Modafinil and Dextroamphetamine as Alertness Promoting Agents in Aviators Performing Extended Operations

DTIC Science & Technology

2010-12-01

sleep management programs or the administration of hypnotics (Babkoff & Krueger, 1992). However, these countermeasures can only work in situations...K. A., Ramspott, S., Sprenger, W. D., and Gardner, S. J. 1997. The efficacy of hypnotic -induced prophylactic naps for the maintenance of alertness...despite its potential risks; or c) there are no animal reproduction studies and no adequate studies in humans. Consequently, women who were

Hypnosis in sport: an Isomorphic Model.

PubMed

Robazza, C; Bortoli, L

1994-10-01

Hypnosis in sport can be applied according to an Isomorphic Model. Active-alert hypnosis is induced before or during practice whereas traditional hypnosis is induced after practice to establish connections between the two experiences. The fundamental goals are to (a) develop mental skills important to both motor and hypnotic performance, (b) supply a wide range of motor and hypnotic bodily experiences important to performance, and (c) induce alert hypnosis before or during performance. The model is based on the assumption that hypnosis and motor performance share common skills modifiable through training. Similarities between hypnosis and peak performance in the model are also considered. Some predictions are important from theoretical and practical points of view.

Desensitization of GABAergic receptors as a mechanism of zolpidem-induced somnambulism.

PubMed

Juszczak, Grzegorz R

2011-08-01

Sleepwalking is a frequently reported side effect of zolpidem which is a short-acting hypnotic drug potentiating activity of GABA(A) receptors. Paradoxically, the most commonly used medications for somnambulism are benzodiazepines, especially clonazepam, which also potentiate activity of GABA(A) receptors. It is proposed that zolpidem-induced sleepwalking can be explained by the desensitization of GABAergic receptors located on serotonergic neurons. According to the proposed model, the delay between desensitization of GABA receptors and a compensatory decrease in serotonin release constitutes the time window for parasomnias. The occurrence of sleepwalking depends on individual differences in receptor desensitization, autoregulation of serotonin release and drug pharmacokinetics. The proposed mechanism of interaction between GABAergic and serotonergic systems can be also relevant for zolpidem abuse and zolpidem-induced hallucinations. It is therefore suggested that special care should be taken when zolpidem is used in patients taking at the same time selective serotonin reuptake inhibitors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Saccadic eye movements as a measure of residual effects: temazepam compared with other hypnotics.

PubMed

Hofferberth, B; Hirschberg; Grotemeyer

1986-01-01

Eye movements are classified into two categories: quickly running saccades and smooth pursuit movements. Saccades are fast conjugate eye movements with a preprogrammed direction, amplitude, and speed course; their purpose is to register new objects in the visual field. The duration and velocity of saccadic eye movements are very much dependent on vigilance. Comparisons were made with a number of psychometric tests [d 2 Durchstreichtest (cross out test), Viennese determination apparatus, and flicker fusion frequency] and the velocity of fast eye movements. The results of three separate investigations are presented. Standardization was undertaken in 100 healthy volunteers, 50 male and 50 female subjects aged between 20 and more than 50 years were included. In an open parallel group study, comparisons were made between various hypnotics with different half-lives (temazepam, flunitrazepam, flurazepam, and phenobarbital). There were 10 healthy volunteers in each group, and medication was taken as a single night-time dose for 7 nights. In a double-blind study, temazepam (20 mg/day) was tested against flunitrazepam (2 mg/day). Dosing lasted 7 days. A marked impairment of the saccadic eye movements was observed with flunitrazepam but not with temazepam. Of all the benzodiazepines tested, only temazepam had no influence on the parameters of the saccade test. These results can be explained by temazepam's short half-life and also by the fact that no active metabolites are formed.

Depressive effects on the central nervous system and underlying mechanism of the enzymatic extract and its phlorotannin-rich fraction from Ecklonia cava edible brown seaweed.

PubMed

Cho, Suengmok; Han, Daeseok; Kim, Seon-Bong; Yoon, Minseok; Yang, Hyejin; Jin, Young-Ho; Jo, Jinho; Yong, Hyeim; Lee, Sang-Hoon; Jeon, You-Jin; Shimizu, Makoto

2012-01-01

Marine plants have been reported to possess various pharmacological properties; however, there have been few reports on their neuropharmacological effects. Terrestrial plants have depressive effects on the central nervous system (CNS) because of their polyphenols which make them effective as anticonvulsants and sleep inducers. We investigated in this study the depressive effects of the polyphenol-rich brown seaweed, Ecklonia cava (EC), on CNS. An EC enzymatic extract (ECEE) showed significant anticonvulsive (>500 mg/kg) and sleep-inducing (>500 mg/kg) effects on the respective mice seizure induced by picrotoxin and on the mice sleep induced by pentobarbital. The phlorotannin-rich fraction (PTRF) from ECEE significantly potentiated the pentobarbital-induced sleep at >50 mg/kg. PTRF had binding activity to the gamma aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. The sleep-inducing effects of diazepam (DZP, a well-known GABA(A)-BZD agonist), ECEE, and PTRF were completely blocked by flumazenil, a well-known antagonist of GABA(A)-BZD receptors. These results imply that ECEE produced depressive effects on CNS by positive allosteric modulation of its phlorotannins on GABA(A)-BZD receptors like DZP. Our study proposes EC as a candidate for the effective treatment of neuropsychiatric disorders such as anxiety and insomnia.

Hypnosis and imaging of the living human brain.

PubMed

Landry, Mathieu; Raz, Amir

2015-01-01

Over more than two decades, studies using imaging techniques of the living human brain have begun to explore the neural correlates of hypnosis. The collective findings provide a gripping, albeit preliminary, account of the underlying neurobiological mechanisms involved in hypnotic phenomena. While substantial advances lend support to different hypotheses pertaining to hypnotic modulation of attention, control, and monitoring processes, the complex interactions among the many mediating variables largely hinder our ability to isolate robust commonalities across studies. The present account presents a critical integrative synthesis of neuroimaging studies targeting hypnosis as a function of suggestion. Specifically, hypnotic induction without task-specific suggestion is examined, as well as suggestions concerning sensation and perception, memory, and ideomotor response. The importance of carefully designed experiments is highlighted to better tease apart the neural correlates that subserve hypnotic phenomena. Moreover, converging findings intimate that hypnotic suggestions seem to induce specific neural patterns. These observations propose that suggestions may have the ability to target focal brain networks. Drawing on evidence spanning several technological modalities, neuroimaging studies of hypnosis pave the road to a more scientific understanding of a dramatic, yet largely evasive, domain of human behavior.

Adrenal hormones and liver cAMP in exercising rats--different modes of anesthesia.

PubMed

Winder, W W; Fuller, E O; Conlee, R K

1983-11-01

We have compared five different modes of anesthesia (iv and ip pentobarbital sodium, ether, CO2, and cervical dislocation) with respect to their effects on liver glycogen, liver adenosine 3',5'-cyclic monophosphate (cAMP), blood glucose and lactate, plasma corticosterone, norepinephrine, and epinephrine in resting rats and in rats run on a treadmill at 26 m/min for 30 min. Ether, CO2, and cervical dislocation were found to be unsuitable due to the marked elevation in plasma catecholamines seen in both resting and exercising rats. Injection of pentobarbital sodium ip required an average of 8 min before onset of surgical anesthesia as opposed to less than 5 s for iv pentobarbital. Exercising rats anesthetized with ip pentobarbital showed markedly lower plasma catecholamines compared with rats given iv pentobarbital. Hepatic cAMP increased in response to exercise in all groups except the ip pentobarbital group. This is most likely due to the long delay between the end of the exercise and freezing of the liver in the ip pentobarbital-anesthetized animals. We conclude that iv injection of pentobarbital is the most suitable method of anesthesia for obtaining accurate measurements of plasma stress hormones, substrates, and metabolites and of hepatic cAMP and glycogen in resting and exercising rats.

Synthesis and anticonvulsant activity of some substituted 1,2,4-thiadiazoles.

PubMed

Gupta, Arun; Mishra, Pradeep; Pandeya, S N; Kashaw, Sushil K; Kashaw, Varsha; Stables, James P

2009-03-01

A series of new substituted 1,2,4-thiadiazoles were synthesized by appropriate route and screened for anticonvulsant, neurotoxic and sedative-hypnotic activity. The structures of the synthesized compounds were confirmed by IR spectroscopy, (13)C NMR and elemental (nitrogen and sulphur) analysis. After i.p. injection of the compounds to mice or rate at doses of 30, 100, and 300 mg/kg, body weights were examined in the maximal electroshock-induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models after 0.5 and 4 h. Rotorod method and phenobarbitone-induced hypnosis potentiation study were employed to examine neurotoxicity and sedative-hypnotic activity, respectively. All the compounds except 4g showed protection against MES screen after 0.5 h. Compounds 3a-c, 4a-c were active at 100 mg/kg dose i.p., whereas remaining compounds showed activity at 300 mg/kg. All 14 compounds except 3g showed neurotoxicity at 100 and 300 mg/kg after 0.5 h. Compounds 3b and 4b showed NT after 4 h. Two compounds 3b and 4g showed significant (p<0.05) percentage increase in sleeping time i.e. 67% and 59%, respectively. It may be concluded that the synthesized compounds were potent against MES-induced seizures than ScPTZ induced and showed low potency as sedative-hypnotic agent which is advantageous.

Foetal stress responses to euthanasia of pregnant sheep.

PubMed

Peisker, Nina; Preissel, Anne-Kathrin; Reichenbach, Horst-Dieter; Schuster, Tibor; Henke, Julia

2010-01-01

The study was designed to evaluate foetal stress responses in midgestational (G1) and near-term (G2) pregnant ewes euthanized either by intravenous administration of pentobarbital (group P) or electrical current (group E). After the ewe's death foetal lambs were delivered by caesarean section and remained attached to the ewe by the umbilical cord. Foetal vitality, reflexes, heart rate, blood pressure, rectal body temperature, venous pCO2, pH and lactic acid were monitored. Additionally, foetal plasma concentrations of pentobarbital were determined in group P. Neither electrocution of the pregnant ewe nor euthanasia of the dam by pentobarbital caused cardiac arrest in foetuses within 25 minutes. G1-foetuses of group P lost significantly faster all body movements and reflexes whereas G2-foetuses of group P took significantly longer in reaching a venous pH < 7.0 and a pCO2 > 13.33 kPa as well as a blood lactate concentration of > 8 mmol/l. Since no scientific evidence has been found yet to what extent the foetal lamb can experience pain and can suffer, the prolonged process of dying for group-E-foetuses due to hypoxia is inconsistent with criteria for humane euthanasia and animal welfare. The administration of pentobarbital to the pregnant ewe, however, might have the potential to induce foetal anaesthesia thereby satisfying the main aspects of the definition of humane euthanasia to a greater extent.

Drug discrimination under two concurrent fixed-interval fixed-interval schedules.

PubMed

McMillan, D E; Li, M

2000-07-01

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent

Controlled Cortical Impact in Swine: Pathophysiology and Biomechanics

DTIC Science & Technology

2005-03-28

et al 3/28/05 free access to food and water until 12 h before anesthesia was induced. After intubation, anesthesia was maintained with a fentanyl ...injury in 10 of these 13 animals. Histological Studies After completion of monitoring, the swine received an overdose of pentobarbital. The brain was

Increasing Ketamine Use for Refractory Status Epilepticus in US Pediatric Hospitals.

PubMed

Keros, Sotirios; Buraniqi, Ersida; Alex, Byron; Antonetty, Annalee; Fialho, Hugo; Hafeez, Baria; Jackson, Michele C; Jawahar, Rachel; Kjelleren, Stephanie; Stewart, Elizabeth; Morgan, Lindsey A; Wainwright, Mark S; Sogawa, Yoshimi; Patel, Anup D; Loddenkemper, Tobias; Grinspan, Zachary M

2017-06-01

Ketamine is an emerging therapy for pediatric refractory status epilepticus. The circumstances of its use, however, are understudied. The authors described pediatric refractory status epilepticus treated with ketamine from 2010 to 2014 at 45 centers using the Pediatric Hospital Inpatient System database. For comparison, they described children treated with pentobarbital. The authors estimated that 48 children received ketamine and pentobarbital for refractory status epilepticus, and 630 pentobarbital without ketamine. Those receiving only pentobarbital were median age 3 [interquartile range 0-10], and spent 30 [18-52] days in-hospital, including 17 [9-28] intensive care unit (ICU) days; 17% died. Median cost was $148 000 [81 000-241 000]. The pentobarbital-ketamine group was older (7 [2-11]) with longer hospital stays (51 [30-93]) and more ICU days (29 [20-56]); 29% died. Median cost was $298 000 [176 000-607 000]. For 71%, ketamine was given ≥1 day after pentobarbital. Ketamine cases per half-year increased from 2 to 9 ( P < .05). Ketamine is increasingly used for severe pediatric refractory status epilepticus, typically after pentobarbital. Research on its effectiveness is indicated.

Determination of sedative hypnotics in sewage sludge by pressurized liquid extraction with high-performance liquid chromatography and tandem mass spectrometry.

PubMed

Arbeláez, Paula; Granados, Judith; Borrull, Francesc; Marcé, Rosa Maria; Pocurull, Eva

2014-12-01

This paper describes a method for the determination of eight sedative hypnotics (benzodiazepines and barbiturates) in sewage sludge using pressurized liquid extraction and liquid chromatography with tandem mass spectrometry. Pressurized liquid extraction operating conditions were optimized and maximum recoveries were reached using methanol under the following operational conditions: 100ºC, 1500 psi, extraction time of 5 min, one extraction cycle, flush volume of 60% and purge time of 120 s. Pressurized liquid extraction recoveries were higher than 88% for all the compounds except for carbamazepine (55%). The repeatability and reproducibility between days, expressed as relative standard deviation (n = 5), were lower than 6 and 10%, respectively. The detection limits for all compounds were lower than 12.5 μg/kg of dry weight. The method was applied to determine benzodiazepines and barbiturates in sewage sludge from urban sewage treatment plants, and carbamazepine showed the highest concentration (7.9-18.9 μg/kg dry weight). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

PubMed

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

2011-01-01

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

Comparison of intraosseous pentobarbital administration and thoracic compression for euthanasia of anesthetized sparrows (Passer domesticus) and starlings (Sturnus vulgaris).

PubMed

Paul-Murphy, Joanne R; Engilis, Andrew; Pascoe, Peter J; Williams, D Colette; Gustavsen, Kate A; Drazenovich, Tracy L; Keel, M Kevin; Polley, Tamsen M; Engilis, Irene E

2017-08-01

OBJECTIVE To compare intraosseous pentobarbital treatment (IPT) and thoracic compression (TC) on time to circulatory arrest and an isoelectric electroencephalogram (EEG) in anesthetized passerine birds. ANIMALS 30 wild-caught adult birds (17 house sparrows [Passer domesticus] and 13 European starlings [Sturnus vulgaris]). PROCEDURES Birds were assigned to receive IPT or TC (n = 6/species/group). Birds were anesthetized, and carotid arterial pulses were monitored by Doppler methodology. Five subdermal braided-wire electrodes were used for EEG. Anesthetic depth was adjusted until a continuous EEG pattern was maintained, then euthanasia was performed. Times from initiation of euthanasia to cessation of carotid pulse and irreversible isoelectric EEG (indicators of death) were measured. Data (medians and first to third quartiles) were summarized and compared between groups within species. Necropsies were performed for all birds included in experiments and for another 6 birds euthanized under anesthesia by TC (4 sparrows and 1 starling) or IPT (1 sparrow). RESULTS Median time to isoelectric EEG did not differ significantly between treatment groups for sparrows (19.0 and 6.0 seconds for TC and IPT, respectively) or starlings (88.5 and 77.5 seconds for TC and IPT, respectively). Median times to cessation of pulse were significantly shorter for TC than for IPT in sparrows (0.0 vs 18.5 seconds) and starlings (9.5 vs 151.0 seconds). On necropsy, most (14/17) birds that underwent TC had grossly visible coelomic, pericardial, or perihepatic hemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that TC might be an efficient euthanasia method for small birds. Digital pressure directly over the heart during TC obstructed venous return, causing rapid circulatory arrest, with rupture of the atria or vena cava in several birds. The authors propose that cardiac compression is a more accurate description than TC for this procedure.

Behavior and Cellular Evidence for Propofol-Induced Hypnosis Involving Brain Glycine Receptors

PubMed Central

Nguyen, Hai T; Li, Ke-yong; da Graca, Ralph L; Delphin, Ellise; Xiong, Ming; Ye, Jiang H

2009-01-01

Background It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. Methods Experiments were conducted in rats, where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and the absence of strychnine (a glycine receptor antagonist), GABAzine (a γ-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and γ-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. Results Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. Additionally, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. Conclusion Strychnine, the glycine receptor antagonist dose-dependently reduced propofol-induced loss of righting reflex in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis. PMID:19194159

Neural correlates of consciousness during general anesthesia using functional magnetic resonance imaging (fMRI).

PubMed

Bonhomme, V; Boveroux, P; Brichant, J F; Laureys, S; Boly, M

2012-01-01

This paper reviews the current knowledge about the mechanisms of anesthesia-induced alteration of consciousness. It is now evident that hypnotic anesthetic agents have specific brain targets whose function is hierarchically altered in a dose-dependent manner. Higher order networks, thought to be involved in mental content generation, as well as sub-cortical networks involved in thalamic activity regulation seems to be affected first by increasing concentrations of hypnotic agents that enhance inhibitory neurotransmission. Lower order sensory networks are preserved, including thalamo-cortical connectivity into those networks, even at concentrations that suppress responsiveness, but cross-modal sensory interactions are inhibited. Thalamo-cortical connectivity into the consciousness networks decreases with increasing concentrations of those agents, and is transformed into an anti-correlated activity between the thalamus and the cortex for the deepest levels of sedation, when the subject is non responsive. Future will tell us whether these brain function alterations are also observed with hypnotic agents that mainly inhibit excitatory neurotransmission. The link between the observations made using fMRI and the identified biochemical targets of hypnotic anesthetic agents still remains to be identified.

Extract from Fructus cannabis activating calcineurin improved learning and memory in mice with chemical drug-induced dysmnesia.

PubMed

Luo, Jing; Yin, Jiang-Hua; Wu, He-Zhen; Wei, Qun

2003-11-01

To investigate the effects of extract from Fructus cannabis (EFC) that can activate calcineurin on learning and memory impairment induced by chemical drugs in mice. Bovine brain calcineurin and calmodulin were isolated from frozen tissues. The activity of calcineurin was assayed using p-nitrophenyl phosphate (PNPP) as the substrate. Step-down type passive avoidance test and water maze were used together to determine the effects of EFC on learning and memory dysfunction. EFC activated calcineurin activity at a concentration range of 0.01-100 g/L. The maximal value of EFC on calcineurin activity (35 %+/-5 %) appeared at a concentration of 10 g/L. The chemical drugs such as scopolamine, sodium nitrite, and 45 % ethanol, and sodium pentobarbital induced learning and memory dysfunction. EFC administration (0.2, 0.4, and 0.8 g/kg, igx7 d) prolonged the latency and decreased the number of errors in the step-down test. EFC, given for 7 d, enhanced the spatial resolution of amnesic mice in water maze test. EFC overcome amnesia of three stages of memory process at the dose of 0.2 g/kg. EFC with an activation role of calcineurin can improve the impaired learning and memory induced by chemical drugs in mice.

Hip/femur fractures associated with the use of benzodiazepines (anxiolytics, hypnotics and related drugs): a methodological approach to assess consistencies across databases from the PROTECT-EU project.

PubMed

Requena, Gema; Huerta, Consuelo; Gardarsdottir, Helga; Logie, John; González-González, Rocío; Abbing-Karahagopian, Victoria; Miret, Montserrat; Schneider, Cornelia; Souverein, Patrick C; Webb, Dave; Afonso, Ana; Boudiaf, Nada; Martin, Elisa; Oliva, Belén; Alvarez, Arturo; De Groot, Mark C H; Bate, Andrew; Johansson, Saga; Schlienger, Raymond; Reynolds, Robert; Klungel, Olaf H; de Abajo, Francisco J

2016-03-01

Results from observational studies may be inconsistent because of variations in methodological and clinical factors that may be intrinsically related to the database (DB) where the study is performed. The objectives of this paper were to evaluate the impact of applying a common study protocol to study benzodiazepines (BZDs) (anxiolytics, hypnotics, and related drugs) and the risk of hip/femur fracture (HFF) across three European primary care DBs and to investigate any resulting discrepancies. To measure the risk of HFF among adult users of BZDs during 2001-2009, three cohort and nested case control (NCC) studies were performed in Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) (Spain), Clinical Practice Research Datalink (CPRD) (UK), and Mondriaan (The Netherlands). Four different models (A-D) with increasing levels of adjustment were analyzed. The risk according to duration and type of BZD was also explored. Adjusted hazard ratios (cohort), odds ratios (NCC), and their 95% confidence intervals were estimated. Adjusted hazard ratios (Model C) were 1.34 (1.23-1.47) in BIFAP, 1.66 (1.54-1.78) in CPRD, and 2.22 (1.55-3.29) in Mondriaan in cohort studies. Adjusted odds ratios (Model C) were 1.28 (1.16-1.42) in BIFAP, 1.60 (1.49-1.72) in CPRD, and 1.48 (0.89-2.48) in Mondriaan in NCC studies. A short-term effect was suggested in Mondriaan, but not in CPRD or BIFAP. All DBs showed an increased risk with the concomitant use of anxiolytic and hypnotic drugs. Applying similar study methods to different populations and DBs showed an increased risk of HFF in BZDs users but differed in the magnitude of the risk, which may be because of inherent differences between DBs. Copyright © 2015 John Wiley & Sons, Ltd.

A Multifaceted GABAA Receptor Modulator: Functional Properties and Mechanism of Action of the Sedative-Hypnotic and Recreational Drug Methaqualone (Quaalude).

PubMed

Hammer, Harriet; Bader, Benjamin M; Ehnert, Corina; Bundgaard, Christoffer; Bunch, Lennart; Hoestgaard-Jensen, Kirsten; Schroeder, Olaf H-U; Bastlund, Jesper F; Gramowski-Voß, Alexandra; Jensen, Anders A

2015-08-01

In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an infamous sedative-hypnotic and recreational drug from the 1960s-1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human α1,2,3,5β2,3γ2S GABAA receptors (GABAARs) expressed in Xenopus oocytes, whereas it displayed highly diverse functionalities at the α4,6β1,2,3δ GABAAR subtypes, ranging from inactivity (α4β1δ), through negative (α6β1δ) or positive allosteric modulation (α4β2δ, α6β2,3δ), to superagonism (α4β3δ). Methaqualone did not interact with the benzodiazepine, barbiturate, or neurosteroid binding sites in the GABAAR. Instead, the compound is proposed to act through the transmembrane β((+))/α((-)) subunit interface of the receptor, possibly targeting a site overlapping with that of the general anesthetic etomidate. The negligible activities displayed by methaqualone at numerous neurotransmitter receptors and transporters in an elaborate screening for additional putative central nervous system (CNS) targets suggest that it is a selective GABAAR modulator. The mode of action of methaqualone was further investigated in multichannel recordings from primary frontal cortex networks, where the overall activity changes induced by the compound at 1-100 μM concentrations were quite similar to those mediated by other CNS depressants. Finally, the free methaqualone concentrations in the mouse brain arising from doses producing significant in vivo effects in assays for locomotion and anticonvulsant activity correlated fairly well with its potencies as a modulator at the recombinant GABAARs. Hence, we propose that the multifaceted functional properties exhibited by methaqualone at GABAARs give rise to its effects as a therapeutic and recreational drug. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats.

PubMed

Cachón, Andrés Uc; Quintal-Novelo, Carlos; Medina-Escobedo, Gilberto; Castro-Aguilar, Gaspar; Moo-Puc, Rosa E

2017-03-04

Several studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl 4 )-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl 4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl 4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl 4 -induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl 4 -induced liver damage in rats.

Stability of 26 Sedative Hypnotics in Six Toxicological Matrices at Different Storage Conditions.

PubMed

Mata, Dani C

2016-10-01

Forensic laboratories are challenged with backlogs that produce turnaround times that vary from days to months. Therefore, drug stability is important for interpretation in both antemortem (blood and urine) and postmortem (blood, brain, liver, stomach contents) cases. In this study, 23 benzodiazepines (2-hydroxyethylflurazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, α-hydroxyalprazolam, α-hydroxytriazolam, alprazolam, bromazepam, chlordiazepoxide, clonazepam, demoxepam, desalkylflurazepam, diazepam, estazolam, flunitrazepam, flurazepam, lorazepam, midazolam, nitrazepam, nordiazepam, oxazepam, phenazepam, temazepam and triazolam) and three sedative hypnotics (zaleplon, zopiclone and zolpidem) were spiked into the six matrices at two different concentrations for each drug. The samples were stored in either a refrigerator (4°C) or freezer (-20°C) and analyzed in triplicate at various time intervals over an 8-month period using an SWGTOX validated method. The concentrations decreased over time regardless of the initial spiked concentration, and the storage conditions had little effect on the decrease of most drugs. Conversion from drug to metabolite was difficult to determine since all 26 drugs were present in each sample. Zopiclone and phenazepam were the least stable drugs; zopiclone was the only drug that completely disappeared in any matrix (both antemortem and postmortem blood). Urine was the most stable matrix with only phenazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, 2-hydroxyethylflurazepam, and zopiclone decreasing >20% over the 8 months in either storage condition. Postmortem blood, the least stable matrix, had only two drugs, zolpidem and bromazepam, decreasing <20% in the 8-month time period. Further experiments on stability of these drugs should be undertaken to remove the freeze-thaw cycle effect and more thoroughly examining drug-metabolite conversion. © The Author 2016. Published by Oxford University Press. All rights reserved. For

Clopidogrel preserves whole kidney autoregulatory behavior in ANG II-induced hypertension

PubMed Central

Osmond, David A.; Zhang, Shali; Pollock, Jennifer S.; Yamamoto, Tatsuo; De Miguel, Carmen

2014-01-01

This study tested the hypothesis that P2Y12 receptor blockade with clopidogrel preserves renal autoregulatory ability during ANG II-induced hypertension. Clopidogrel was administered orally to male Sprague-Dawley rats chronically infused with ANG II. After 14 days of treatment, whole kidney autoregulation of renal blood flow was assessed in vivo in pentobarbital-anesthetized rats using an ultrasonic flow probe placed around the left renal artery. In ANG II-vehicle-treated rats, decreasing arterial pressure over a range from 160 to 100 mmHg resulted in a 25 ± 5% decrease in renal blood flow, demonstrating a significant loss of autoregulation with an autoregulatory index of 0.66 ± 0.15. However, clopidogrel treatment preserved autoregulatory behavior in ANG II-treated rats to levels indistinguishable from normotensive sham-operated (sham) rats (autoregulatory index: 0.04 ± 0.14). Compared with normotensive sham-vehicle-treated rats, ANG II infusion increased renal CD3-positive T cell infiltration by 66 ± 6%, induced significant thickening of the preglomerular vessels and glomerular basement membrane and increased glomerular collagen I deposition, tubulointerstitial fibrosis, damage to the proximal tubular brush border, and protein excretion. Clopidogrel significantly reduced renal infiltration of T cells by 39 ± 9% and prevented interstitial artery thickening, ANG II-induced damage to the glomerular basement membrane, deposition of collagen type I, and tubulointerstitial fibrosis, despite the maintenance of hypertension. These data demonstrate that systemic P2Y12 receptor blockade with clopidogrel protects against impairment of autoregulatory behavior and renal vascular injury in ANG II-induced hypertension, possibly by reducing renal T cell infiltration. PMID:24477682

Advancing Novel Anesthetics: Pharmacodynamic and Pharmacokinetic Studies of Cyclopropyl-Methoxycarbonyl Metomidate in Dogs

PubMed Central

Campagna, Jason A.; Pojasek, Kevin; Grayzel, David; Randle, John; Raines, Douglas E.

2014-01-01

Background Cyclopropyl-methoxycarbonyl metomidate (CPMM, also known as ABP-700) is a second-generation “soft” (i.e., metabolically-labile) etomidate analogue. The purpose of these studies was to characterize CPMM's pharmacology in beagle dogs in preparation for potential first in human phase 1 clinical trials. Methods CPMM's and etomidate's hypnotic activity and duration of action were assessed using loss of righting reflex and anesthesia score assays in three or four dogs. Their pharmacokinetics were defined after single bolus administration and single bolus followed by 2-h infusion. Adrenocortical recovery times after single bolus followed by 2-h infusion of CPMM, propofol, etomidate, and vehicle were measured using an adrenocorticotropic hormone stimulation test. Results Compared to etomidate, CPMM was half as potent as a hypnotic (ED50 ~ 0.8 mg/kg), more rapidly metabolized, and had a shorter duration of sedative-hypnotic action. Recovery times after CPMM administration were also independent of infusion duration. After hypnotic infusion, adrenocorticotropic hormone-stimulated plasma cortisol concentrations were 4- to 27-fold higher in dogs that received CPMM versus etomidate. Adrenocortical recovery was faster in dogs after CPMM infusion versus etomidate infusion (half-time: 215 min vs. 1623 min, respectively). Adrenocortical responsiveness assessed 90 min after CPMM infusion was not significantly different from that after propofol infusion. Conclusion Our studies in dogs confirm that CPMM has hypnotic and adrenocortical recovery profiles that are superior than those of etomidate, supporting the continued development of CPMM as a clinical sedative-hypnotic to be used as a single bolus and by continuous infusion to induce and maintain general anesthesia or procedural sedation. PMID:25170571

Prevalence of sleep deficiency and use of hypnotic drugs in astronauts before, during, and after spaceflight: an observational study.

PubMed

Barger, Laura K; Flynn-Evans, Erin E; Kubey, Alan; Walsh, Lorcan; Ronda, Joseph M; Wang, Wei; Wright, Kenneth P; Czeisler, Charles A

2014-09-01

Sleep deprivation and fatigue are common subjective complaints among astronauts. Previous studies of sleep and hypnotic drug use in space have been limited to post-flight subjective survey data or in-flight objective data collection from a small number of crew members. We aimed to characterise representative sleep patterns of astronauts on both short-duration and long-duration spaceflight missions. For this observational study, we recruited crew members assigned to Space Transportation System shuttle flights with in-flight experiments between July 12, 2001, and July 21, 2011, or assigned to International Space Station (ISS) expeditions between Sept 18, 2006, and March 16, 2011. We assessed sleep-wake timing objectively via wrist actigraphy, and subjective sleep characteristics and hypnotic drug use via daily logs, in-flight and during Earth-based data-collection intervals: for 2 weeks scheduled about 3 months before launch, 11 days before launch until launch day, and for 7 days upon return to Earth. We collected data from 64 astronauts on 80 space shuttle missions (26 flights, 1063 in-flight days) and 21 astronauts on 13 ISS missions (3248 in-flight days), with ground-based data from all astronauts (4014 days). Crew members attempted and obtained significantly less sleep per night as estimated by actigraphy during space shuttle missions (7·35 h [SD 0·47] attempted, 5·96 h [0·56] obtained), in the 11 days before spaceflight (7·35 h [0·51], 6·04 h [0·72]), and about 3 months before spaceflight (7·40 h [0·59], 6·29 h [0·67]) compared with the first week post-mission (8·01 h [0·78], 6·74 h [0·91]; p<0·0001 for both measures). Crew members on ISS missions obtained significantly less sleep during spaceflight (6·09 h [0·67]), in the 11 days before spaceflight (5·86 h [0·94]), and during the 2-week interval scheduled about 3 months before spaceflight (6·41 h [SD 0·65]) compared with in the first week post-mission (6·95 h [1·04]; p<0·0001). 61 (78

The history of barbiturates a century after their clinical introduction

PubMed Central

López-Muñoz, Francisco; Ucha-Udabe, Ronaldo; Alamo, Cecilio

2005-01-01

The present work offers an analysis of the historical development of the discovery and use of barbiturates in the field of psychiatry and neurology, a century after their clinical introduction. Beginning with the synthesis of malonylurea by von Baeyer in 1864, and up to the decline of barbiturate therapy in the 1960s, it describes the discovery of the sedative properties of barbital, by von Mering and Fischer (1903), the subsequent synthesis of phenobarbital by this same group (1911), and the gradual clinical incorporation of different barbiturates (butobarbital, amobarbital, secobarbital, pentobarbital, thiopental, etc). We describe the role played in therapy by barbiturates throughout their history: their traditional use as sedative and hypnotic agents, their use with schizophrenic patients in so-called “sleep cures” (Klaesi, Cloetta), the discovery of the antiepileptic properties of phenobarbital (Hauptmann) and their use in the treatment of epilepsy, and the introduction of thiobarbiturates in intravenous anesthesia (Lundy, Waters). We also analyze, from the historical perspective, the problems of safety (phenomena of dependence and death by overdose) which, accompanied by the introduction of a range of psychoactive drugs in the 1950s, brought an end to barbiturate use, except in specific applications, such as the induction of anesthesia and the treatment of certain types of epileptic crisis. PMID:18568113

The possible role of human milk nucleotides as sleep inducers.

PubMed

Sánchez, Cristina L; Cubero, Javier; Sánchez, Javier; Chanclón, Belén; Rivero, Montserrat; Rodríguez, Ana B; Barriga, Carmen

2009-02-01

Breast-milk contains a potent mixture of diverse components, such as the non-protein nitrogen fraction which includes nucleotides, whose variation in levels is evident throughout lactation. In addition, these substances play an important role in sleep homeostasis. In the present study, human milk samples were analyzed using a capillary electrophoresis system. The rhythmicity of each nucleotide was studied by cosinor analysis. It was found that the nucleotides 5'AMP, 5'GMP, 5'CMP, and 5'IMP have significant (P < 0.05) circadian rhythms, the acrophases of the first two being during the night, and of the latter two during the day. While 5'UMP did not show a clear circadian rhythm, there was an increase in its levels at night. In conclusion, the rise in nocturnal levels of 5'AMP, 5'GMP, and 5'UMP could be involved in inducing the 'hypnotic' action of breast-milk at night in the infant.

Hepatoprotective activity of Phyllanthus reticulatus.

PubMed

Das, Biplab K; Bepary, Sukumar; Datta, Bidyut K; Chowdhury, Ak Azad; Ali, Mohammad Shawkat; Rouf, Abu Shara Shamsur

2008-10-01

Two partially purified organic fractions designated by PR1 and PR2 of the fat free ethanol (95%) extract of aerial parts of Phyllanthus reticulatus were tested for the hepatoprotective activity in rats against CCl(4)-induced liver damage. The rats receiving the fractions showed promising hepatoprotective activity as evident from significant changes of pentobarbital-induced sleeping time, changes in serum levels of sGPT, sGOT, sALP and bilirubin and also from histopathological changes as compared to CCl(4)-intoxicated rats.

Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry for the Quantitation of Seventeen Sedative Hypnotics in Six Common Toxicological Matrices.

PubMed

Mata, Dani C; Davis, John F; Figueroa, Ariana K; Stanford, Mary June

2016-01-01

An ultra performance liquid chromatography triple quadrupole mass spectrometry (LC-MS-MS) method for the quantification of 14 benzodiazepines and three sedative hypnotics is presented. The fast and inexpensive assay was developed for California's Orange County Crime Lab for use in antemortem (AM) and postmortem casework. The drugs were rapidly cleaned up from AM blood, postmortem blood, urine, liver, brain and stomach contents using DPX(®) Weak Anion Exchange (DPX WAX) tips fitted on a pneumatic extractor, which can process up to 48 samples at one time. Assay performance was determined for validation based on recommendations by the Scientific Working Group for Forensic Toxicology for linearity, limit of quantitation, limit of detection, bias, precision (within run and between run), dilution integrity, carry-over, selectivity, recovery, ion suppression and extracted sample stability. Linearity was verified using the therapeutic and toxic ranges of all 17 analytes. Final verification of the method was confirmed by four analysts using 20 blind matrix matched samples. All results were within 20% of each other and the expected value. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reinforcement magnitude modulation of rate dependent effects in pigeons and rats.

PubMed

Ginsburg, Brett C; Pinkston, Jonathan W; Lamb, R J

2011-08-01

Response rate can influence the behavioral effects of many drugs. Reinforcement magnitude may also influence drug effects. Further, reinforcement magnitude can influence rate-dependent effects. For example, in an earlier report, we showed that rate-dependent effects of two antidepressants depended on reinforcement magnitude. The ability of reinforcement magnitude to interact with rate-dependency has not been well characterized. It is not known whether our previous results are specific to antidepressants or generalize to other drug classes. Here, we further examine rate-magnitude interactions by studying effects of two stimulants (d-amphetamine [0.32-5.6 mg/kg] and cocaine [0.32-10 mg/kg]) and two sedatives (chlordiazepoxide [1.78-32 mg/kg] and pentobarbital [1.0-17.8 mg/kg]) in pigeons responding under a 3-component multiple fixed-interval (FI) 300-s schedule maintained by 2-, 4-, or 8-s of food access. We also examine the effects of d-amphetamine [0.32-3.2 mg/kg] and pentobarbital [1.8-10 mg/kg] in rats responding under a similar multiple FI300-s schedule maintained by 2- or 10- food pellet (45 mg) delivery. In pigeons, cocaine and, to a lesser extent, chlordiazepoxide exerted rate-dependent effects that were diminished by increasing durations of food access. The relationship was less apparent for pentobarbital, and not present for d-amphetamine. In rats, rate-dependent effects of pentobarbital and d-amphetamine were not modulated by reinforcement magnitude. In conclusion, some drugs appear to exert rate-dependent effect which are diminished when reinforcement magnitude is relatively high. Subsequent analysis of the rate-dependency data suggest the effects of reinforcement magnitude may be due to a diminution of drug-induced increases in low-rate behavior that occurs early in the fixed-interval. (c) 2011 APA, all rights reserved.

Oxidative metabolism of limbic structures after acute administration of diazepam, alprazolam and zolpidem.

PubMed

González-Pardo, Héctor; Conejo, Nélida M; Arias, Jorge L

2006-08-30

The effects of acute administration of two benzodiazepines and a non-benzodiazepine hypnotic on behavior and brain metabolism were evaluated in rats. After testing the behavioral action of the benzodiazepines on the open field and the elevated plus-maze, the effects of the three drugs on neuronal metabolism of particular limbic regions were measured using cytochrome c oxidase (CO) histochemistry. Diazepam (5 mg/kg i.p.) and alprazolam (0.5 mg/kg i.p.) induced clear anxiolytic effects and a decrease in locomotion, whereas zolpidem (2 mg/kg i.p.) caused an intense hypnotic effect. The anxiolytic effects of alprazolam were distinguishable from diazepam due to the pharmacological and clinical profile of this triazolobenzodiazepine. CO activity decreased significantly in almost all the limbic regions evaluated after zolpidem administration. However, significant prominent decreases in CO activity were found after diazepam treatment in the medial mammillary nucleus, anteroventral thalamus, cingulate cortex, dentate gyrus and basolateral amygdala. Alprazolam caused similar decreases in CO activity, with the exception of the prelimbic and cingulate cortices, where significant increases were detected. In agreement with previous studies using other functional mapping techniques, our results indicate that particular benzodiazepines and non-benzodiazepine hypnotics induce selective changes in brain oxidative metabolism.

Effect of nicotinic acid on the sleep time and tolerance induced by ethanol in the rat

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

Basilio, C.; Toro, A.; Yojay, L.

The intraperitoneal (i.p.) administration (50 mg/kg) of nicotinic acid (NA), markedly decreased the sleep time of rats pretreated (10 min before), post-treated (10 min after) or simultaneously treated with ethanol (4 g/Kg i.p.). A similar effect was observed on the sleep time induced by pentobarbital (37 mg/Kg i.p.). Blood alcohol levels (BAL) were the same or slightly higher in the animals pretreated with NA than in the control animals pre-injected with saline. Nicotinamide and NAD had no effect. A total of three doses of ethanol, each one administered weekly or biweekly, induced tolerance, which persisted for approximately six weeks. Aftermore » this period, a hypersensitivity to ethanol appeared to develop. This phenomenon was not observed when NA was pre-injected 10 min before each dose of ethanol. The sleep time of the latter animals did not change neither during the treatment period nor after six weeks without any treatment. BAL were slightly higher in NA treated than in control animals. The authors concluded that the effect of NA on the sleep time and tolerance induced by ethanol is not due to an increased rate of its metabolism and/or elimination but to a long-lasting effect that decreases the sensitivity of the nervous cells to ethanol. The mechanisms involved in the shortening of the sleep time as well as those responsible for the loss of the capacity to develop tolerance are under current investigation.« less

The utility of bispectral index monitoring for prevention of rocuronium-induced withdrawal movement in children

PubMed Central

Lim, Byung Gun; Lee, Il Ok; Kim, Young Sung; Won, Young Ju; Kim, Heezoo; Kong, Myoung Hoon

2017-01-01

Abstract Background: This study was designed to determine whether a deep hypnotic state with a bispectral index (BIS) value less than 40 could alleviate withdrawal movement (WM) upon rocuronium injection during anesthesia induction in children. Methods: Finally, 135 healthy children (3–12 years) scheduled for minor elective surgery were studied. Without premedication, anesthesia was induced with thiopental sodium 5 mg/kg. Patients were randomized into 2 groups (control vs experimental) and then by virtue of rocuronium injection time, patients in the experimental group were allocated into 2 groups, as follows: in the control group (group C; n = 45), rocuronium 0.6 mg/kg was administered at the loss of eyelash reflex; in the 1st experimental group, rocuronium 0.6 mg/kg was administered when BIS fell to less than 40 (group T; n = 45); however, if BIS did not fall below 40 after thiopental sodium administration, manual ventilation was provided with oxygen 6 L/minute using sevoflurane 8% and then rocuronium was administered when BIS fell below 40 (the 2nd experimental group, group S; n = 45). Rocuronium-induced WM was evaluated using a 4-point scale (no movement; movement/withdrawal involving the arm only; generalized response, with movement/withdrawal of more than 1 extremity, but no requirement for restraint of the body; and generalized response which required restraint of the body and caused coughing or breath-holding). Results: No significant differences were found among the groups for patient characteristics including age, sex, height, and location of venous cannula. However, body weight, height, and body mass index in group S were all smaller than those in group T. The incidence of WM caused by rocuronium was 100% in group C, 95.6% in group T, and 80% in group S, and was significantly lower in group S than in group C. The grade of WM was 3.7 ± 0.6 in group C, 3.2 ± 0.9 in group T, and 2.6 ± 1.0 in group S. It was significantly

Analgesic, diuretic, and anti-inflammatory principle from Scoparia dulcis.

PubMed

Ahmed, M; Shikha, H A; Sadhu, S K; Rahman, M T; Datta, B K

2001-08-01

Scoparinol, a diterpene, isolated from Scoparia dulcis showed significant analgesic (p < 0.001) and anti-inflammatory activity (p < 0.01) in animals. A sedative action of scoparinol was demonstrated by a marked potentiation of pentobarbital-induced sedation with a significant effect on both onset and duration of sleep (p < 0.05). Measurement of urine volume after administration of scoparinol indicated its significant diuretic action.

Blood-brain barrier alteration after microwave-induced hyperthermia is purely a thermal effect: I. Temperature and power measurements

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

Moriyama, E.; Salcman, M.; Broadwell, R.D.

The effect of microwave-induced hyperthermia on the blood-brain barrier was studied in 21 Sprague-Dawley rats. Under sodium pentobarbital anesthesia, animals were place in a stereotactic frame, and an interstitial microwave antenna operating at 2450 MHz was inserted in a bony groove drilled parallel to the sagittal suture. Some antennae were equipped with an external cooling jacket. Temperature measurements were made lateral to the antenna by fluoroptical thermometry, and power was calculated from the time-temperature profile. Five minutes prior to termination of microwave irradiation, horseradish peroxidase (1 mg/20 g body weight) was injected intravenously. Extravasation of horseradish peroxidase was observed inmore » brain tissue heated above 44.3 degrees C for 30 minutes and at 42.5 degrees C for 60 minutes. Microwave irradiation failed to open the blood-brain barrier when brain temperatures were sustained below 40.3 degrees C by the cooling system. Extravasation of blood-borne peroxidase occurred at sites of maximal temperature elevation, even when these did not coincide with the site of maximum power density. The data suggest that microwave-induced hyperthermia is an effective means for opening the blood-brain barrier and that the mechanism is not related to the nonthermal effect of microwaves.« less

Epidemiological, clinical and sleep laboratory evaluations of insomnia

NASA Technical Reports Server (NTRS)

Bixler, E. O.; Kales, A.; Kales, J. D.

1975-01-01

Epidemiological studies have contributed to the understanding of the total scope of the insomnia problem, both in terms of the incidence of sleep difficulties, and the extent and frequency of hypnotic drug use. Clinical studies - at the Sleep Research and Treatment Center - have been used to evaluate the medical, psychological, pharmacological and situational factors contributing to insomnia, and to evaluate the psychotherapy and chemotherapy best suited to treatment of insomnia. The sleep laboratory studies were of two types: (1) the study of sleep induction, sleep maintenance, and sleep stages, and (2) the use of hypnotic drugs, emphasizing their effectiveness in inducing and maintaining sleep, and the duration of this effectiveness.

Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis.

PubMed

Wang, Bin; Jiang, Junli; Yang, Jun; Chen, Jun; Zhu, Zhaoqiong; Liu, Jin; Zhang, Wensheng

2017-11-15

ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS). Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration. The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups. ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

The volatile anesthetic isoflurane induces ecto-5′-nucleotidase (CD73) to protect against renal ischemia and reperfusion injury

PubMed Central

Kim, Mihwa; Ham, Ahrom; Kim, Joo Yun; Brown, Kevin M.; D’Agati, Vivette D.; Lee, H. Thomas

2013-01-01

The volatile anesthetic isoflurane protects against renal ischemia and reperfusion injury by releasing renal tubular TGF-β1. Since adenosine is a powerful cytoprotective molecule, we tested whether TGF-β1 generated by isoflurane induces renal tubular ecto-5′-nucleotidase (CD73) and adenosine to protect against renal ischemia and reperfusion injury. Isoflurane induced new CD73 synthesis and increased adenosine generation in cultured kidney proximal tubule cells and in mouse kidney. Moreover, a TGF-β1 neutralizing antibody prevented isoflurane-mediated induction of CD73 activity. Mice anesthetized with isoflurane after renal ischemia and reperfusion had significantly reduced plasma creatinine and decreased renal tubular necrosis, neutrophil infiltration and apoptosis compared to pentobarbital-anesthetized mice. Isoflurane failed to protect against renal ischemia and reperfusion injury in CD73 deficient mice, in mice pretreated with a selective CD73 inhibitor or mice treated with an adenosine receptor antagonist. The TGF-β1 neutralizing antibody or the CD73 inhibitor attenuated isoflurane-mediated protection against HK-2 cell apoptosis. Thus, isoflurane causes TGF-β1-dependent induction of renal tubular CD73 and adenosine generation to protect against renal ischemia and reperfusion injury. Modulation of this pathway may have important therapeutic implications to reduce morbidity and mortality arising from ischemic acute kidney injury. PMID:23423261

Retention of sequential drug discriminations under fixed-interval schedules for long time periods without training.

PubMed

Li, Mi; McMillan, Donald E

2003-08-22

The experiments showed that sequential drug discriminations can be learned and retained under a fixed-interval (FI) schedule for more than 18 months without additional training under a complex three-choice procedure. Pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg D-amphetamine, and saline. After responding stabilized, dose-response curves were determined for other drugs. Subsequently, pentobarbital was replaced with 5 mg/kg morphine as a training drug, and D-amphetamine was replaced with 30 mg/kg caffeine. After the pigeons learned these new discriminations, dose-response curves were redetermined. Initially, chlordiazepoxide substituted for pentobarbital, cocaine substituted for D-amphetamine, and nicotine partially substituted for D-amphetamine. Morphine, Delta9-tetrahydrocannabinol, and caffeine did not substitute for either drug. After retraining with morphine and caffeine, responding occurred on the pentobarbital/morphine key after pentobarbital, chlordiazepoxide and morphine and on the D-amphetamine/caffeine key after D-amphetamine, cocaine and caffeine. After nicotine and Delta9-tetrahyrdocannabinol, responding occurred on the saline key. These data show that drug discriminations learned under fixed-interval schedules are retained for long time periods, even when discrimination training with other drugs occurs during the retention period.

Anticonvulsants for Nerve Agent-Induced Seizures: The Influence of the Therapeutic Dose of Atropine

DTIC Science & Technology

2007-01-01

were euthanized with an overdose of sodium pentobarbital (75 in GA-, GD-, and VR-exposed animals. mg/kg i.p.) and then perfused through the aorta...less atropine for competition at the cholin - of atropine and 2-PAM, equivalent to three sets of the ergic receptors. This may also explain the longer...against soman poisoning by pretreatment with pyridustig- is also dependent on the ability of atropine to block cholin - mine. J Pharm Pharmacol 31:29,5-299

In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract

PubMed Central

Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

2016-01-01

Background: Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. Objective: The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). Materials and Methods: The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. Results: The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. Conclusion: The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. SUMMARY Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening

In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract.

PubMed

Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

2016-01-01

Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae . The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. The LD 50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant ( P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant ( P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant ( P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. Anxiety is implicated in the number of psychiatric disorders In vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening test in mice and Rota-.rod test.The GABAergic system plays a

The Effect of Liquid Gun Propellant (LGP) on Skin.

DTIC Science & Technology

1992-02-27

sodium lauryl sulfate ) decreased the barrier properties of hairless guinea pig skin to the greatest extent after I day, and the barrier returned to normal...San Francisco, CA. Wilhelm K.-P., Surber, C. and Maibach, H.I. Effect of sodium lauryl sulfate - induced skin irritation on in vivo percutaneous...NJ), followed by an intravenous injection of sodium pentobarbital (18 mg/kg, Anthony Products, Arcadia, CA). A Padgett Electro Dermatome (Padgett

Involvement of adrenergic and serotonergic nervous mechanisms in allethrin-induced tremors in mice.

PubMed

Nishimura, M; Obana, N; Yagasaki, O; Yanagiya, I

1984-05-01

Oral or intravenous administration of allethrin, a synthetic derivative of the pirethrin-based insecticides, produces neurotoxic symptoms consisting of mild salivation, hyperexcitability, tremors and convulsions which result in death. Intracerebroventricular injection of allethrin to mouse at about one-nineth the dose of intravenous administration, produced qualitatively identical but less prominent symptoms, indicating that at least some of the symptoms may be originated in the central nervous system. To investigate the mechanism of action of the compound, we studied the ability of agents which alter neurotransmission to prevent or potentiate the effect of convulsive doses of technical grade (15.5% cis, 84.5% trans) allethrin. Intraperitoneal pretreatment with drugs which block noradrenergic receptors or norepinephrine synthesis, such as pentobarbital, chlorpromazine, phentolamine, phenoxybenzamine and reserpine, depressed the tremor induced by allethrin. The inhibitory effect of reserpine was reversed by phenylephrine. Both the serotonergic blocker, methysergide, and the serotonin depletor, rho-chlorphenylalanine, potentiated the effect of allethrin. The potentiating effect of methysergide was antagonized by 5-hydroxytryptamine. However, intracerebroventricular administration of methysergide was ineffective in potentiating the effect of allethrin. alpha 2- and beta-adrenoceptor blockers, muscarinic antagonists, GABA mimenergics and morphine had no effect. These results suggest that allethrin produces its neurotoxic responses in mice by acting on the brain and spinal levels. Furthermore, adrenergic excitatory and serotonergic inhibitory mechanisms may be involved in the neural pathway through which the allethrin-induced tremor is evoked.

Hypnotic relaxation vs amitriptyline for tension-type headache: let the patient choose.

PubMed

Ezra, Yacov; Gotkine, Marc; Goldman, Sylvie; Adahan, Haim Moshe; Ben-Hur, Tamir

2012-05-01

Although both pharmacological and behavioral interventions may relieve tension-type headache, data are lacking regarding treatment preference, long-term patient compliance, and feasibility of behavioral intervention in a standard neurological outpatient clinic setting. To describe patient choice, long-term compliance, and clinical outcome in a neurological clinic setting where patients are given the choice of the approach they wish to pursue. Patients presenting to the headache clinic with a diagnosis of tension-type headache that justified prophylactic therapy (frequent episodic tension-type headache or chronic tension-type headache) were given the choice of amitriptyline (AMT) treatment or hypnotic relaxation (HR), and were treated accordingly. Patients were given the option to cross-over to the other treatment group at each visit. HR was performed during standard length neurology clinic appointments by a neurologist trained to perform hypnosis (Y.E.). Follow-up interviews were performed between 6 and 12 months following treatment initiation to evaluate patient compliance, changes in headache frequency or severity, and quality-of-life parameters. Ninety-eight patients were enrolled, 92 agreed to receive prophylactic therapy of some kind. Fifty-three (57.6%) patients chose HR of which 36 (67.9%) actually initiated this treatment, while 39 (42.4%) chose pharmacological therapy with AMT of which 25 (64.1%) patients actually initiated therapy. Patients with greater analgesic use were more likely to opt for AMT (P= .0002). Eleven of the patients initially choosing AMT and 2 of the patients initially choosing HR crossed over to the other group. Seventy-four percent of the patients in the HR group and 58% of patients in the AMT group had a 50% reduction in the frequency of headaches (P= .16). Long-term adherence to treatment with HR exceeded that of AMT. At the end of the study period, 26 of 47 patients who tried HR compared with 10 of 27 who tried AMT continued

Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats

PubMed Central

Behmenburg, Friederike; Dorsch, Marianne; Huhn, Ragnar; Mally, David; Heinen, André; Hollmann, Markus W.; Berger, Marc M.

2015-01-01

Background Mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels are involved in myocardial ischemic preconditioning. Their role in sildenafil-induced cardioprotection is unknown. We investigated whether sildenafil-induced acute cardioprotection is mediated by activation of mBKCa channels in the rat heart in vitro. Methods Male Wistar rats (n = 8 per group) were randomized and anesthetized with pentobarbital (90 mg/kg). Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. Hearts underwent 30 min of global ischemia followed by 60 min of reperfusion. At the end of the experiments infarct size was determined by TTC staining. In the control group rats were not further treated. Sildenafil (3 μM) was administered over 10 min before the beginning of ischemia. The mBKCa channel inhibitor paxilline (1 μM) was administered with and without sildenafil before the onset of ischemia. The pathway underlying sildenafil-induced cardioprotection was further investigated with the protein kinase G blocker KT5823 (1 μM). Myocardial cGMP concentration was measured by ELISA. Data (mean±SD) were analysed with a one and two-way analysis of variance as appropriate. Results In control animals infarct size was 52±8%. Sildenafil increased cGMP concentration and reduced infarct size to 35±6% (P<0.05 vs. control). Paxilline and KT5823 completely blocked sildenafil-induced cardioprotection (paxilline+sildenafil: 50±8%, KT5823+sildenafil: 45±8%; both P<0.05 vs. sildenafil). Functional heart parameters and coronary flow were not different between the study groups. Conclusion This study shows that in male rats protein kinase G-dependent opening of mBKCa channels plays a pivotal role in sildenafil-induced cardioprotection. PMID:26671662

Effects of Alprazolam, Zolpidem and Zopiclone, and of chronic inflammation on peripheral experimental algesia in Wistar rats.

PubMed

Zdrîncă, Mihaela; Muţiu, Gabriela; Bogdan, Maria; Dobjanschi, Luciana; Antonescu, Angela; Moş, Ioana; Mureşan, Mariana; Zdrîncă, M; Antonescu, Andreea

2011-01-01

In the literature, there are some data which indicate that benzodiazepines and other chemical compounds with the same mechanism of action (Diazepam, Chlordiazepoxide, Lorazepam, Zopiclone, etc.) also have other effects. We investigated the effects of experimental chronic inflammation under the administration of some tranquilizers and hypnotics on peripheral algesia induced in rats by "writhing test". Chronic inflammation was induced by "cotton wool granuloma" technique. The "writhing test" consisted in intraperitoneal injection of an irritant agent (acetic acid 0.0025%, 0.4 mL). The animal reacts with a characteristic stretching behavior called writhing. A writhe is indicated by stretching of the abdomen with simultaneous stretching of at least one hind limb. Then, the animals were placed individually into glass beakers and 5 minutes were allowed to elapse. The rats were then observed for a period of 10 minutes and the number of writhes is recorded for each animal. Three drugs were administered by gastric probe: Alprazolam 1 mg/kg, Zolpidem 10 mg/kg and Zopiclone 10 mg/kg. Alprazolam is a triazolobenzodiazepine derivative used as a tranquilizer. Zolpidem is an imidazopyridine with marked sedative-hypnotic effect and it has the same mechanism of action like benzodiazepines. Zopiclone is a cyclopyrrolone with sedative-hypnotic effect used as hypnotic and acts like benzodiazepines. After that, the animals were sacrificed and the weight of cotton wool granuloma was determined. In the same time, the histopatological aspect of granulomatous inflammation was studied. It was found that experimental proliferative inflammation under the action of these drugs was accompanied by a peripheral analgesic activity in "writhing test". The mechanisms of these effects are not fully elucidated. Some explanations are: they act as agonists or antagonists on algesia and inflammation mediators and they have a stimulating effect on peripheral ω3-benzodiazepine receptors ("peripheral

Leader’s Guide to Crew Endurance

DTIC Science & Technology

1997-08-01

Dwight Lindsey, Systems Safety Branch, USASC Ms. Betty Marcum, USASC, editor LOCAL REPRODUCTION IS AUTHORIZED AND ENCOURAGED Foreword Stress, fatigue...Avoid using hypnotics to induce sleep in soldiers who have been kept awake on stimulants (and vice versa). "* Stimulants are only a temporary solution

Influence of anesthesia on cerebral blood flow, cerebral metabolic rate, and brain functional connectivity.

PubMed

Bonhomme, Vincent; Boveroux, Pierre; Hans, Pol; Brichant, Jean François; Vanhaudenhuyse, Audrey; Boly, Melanie; Laureys, Steven

2011-10-01

To describe recent studies exploring brain function under the influence of hypnotic anesthetic agents, and their implications on the understanding of consciousness physiology and anesthesia-induced alteration of consciousness. Cerebral cortex is the primary target of the hypnotic effect of anesthetic agents, and higher-order association areas are more sensitive to this effect than lower-order processing regions. Increasing concentration of anesthetic agents progressively attenuates connectivity in the consciousness networks, while connectivity in lower-order sensory and motor networks is preserved. Alteration of thalamic sub-cortical regulation could compromise the cortical integration of information despite preserved thalamic activation by external stimuli. At concentrations producing unresponsiveness, the activity of consciousness networks becomes anticorrelated with thalamic activity, while connectivity in lower-order sensory networks persists, although with cross-modal interaction alterations. Accumulating evidence suggests that hypnotic anesthetic agents disrupt large-scale cerebral connectivity. This would result in an inability of the brain to generate and integrate information, while external sensory information is still processed at a lower order of complexity.

The predictive utility of hypnotizability: the change in suggestibility produced by hypnosis.

PubMed

Milling, Leonard S; Coursen, Elizabeth L; Shores, Jessica S; Waszkiewicz, Jolanta A

2010-02-01

The predictive utility of hypnotizability, conceptualized as the change in suggestibility produced by a hypnotic induction, was investigated in the suggested reduction of experimental pain. One hundred and seventy-three participants were assessed for nonhypnotic imaginative suggestibility. Thereafter, participants experienced hypnotic and nonhypnotic imaginative analgesia suggestions, counterbalanced for order. Hypnotic suggestibility was then assessed. Hypnotizability, operationalized as hypnotic suggestibility with imaginative suggestibility statistically controlled (Braffman & Kirsch, 1999), predicted intraindividual differences in responding to the hypnotic and imaginative analgesia suggestions. Higher hypnotizability was associated with relatively greater response to the hypnotic analgesia suggestion than to the imaginative analgesia suggestion. Operationalized in this way, hypnotizability may be a useful predictor of the effect of adding a hypnotic induction to a specific imaginative suggestion.

An assessment of the potential of protopine to inhibit microsomal drug metabolising enzymes and prevent chemical-induced hepatotoxicity in rodents.

PubMed

Janbaz, K H; Saeed, S A; Gilani, A H

1998-09-01

The potential of protopine to inhibit microsomal drug metabolising enzymes (MDM E) and prevent paracetamol- and CCl4-induced hepatotoxicity was studied in rats. Paracetamol at the dose of 640 mg kg-1 produced hepatic damage in rats as manifested by the rise in serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) to 972+/-186 and 624+/-131 IU (mean+/-sem; n=10), respectively, compared to respective control values of 101+/-29 and 64+/-18 IU. Pretreatment of rats with protopine (11 mg kg-1, orally twice daily for 2 days) lowered significantly the respective serum AST and ALT levels (P<0.05) to 289+/-52 and 178+/-43 IU. The hepatotoxic dose of CCl4 (1.5 ml kg-1; orally) raised serum AST and ALT levels to 543+/-89 and 387+/-69 IU (mean+/-sem; n=10), respectively, compared to respective control values of 98+/-28 and 56+/-17 IU. The same dose of protopine (11 mg kg-1) was able to prevent significantly (P<0.05), the CCl4-induced rise in serum enzymes and the estimated values of AST and ALT were 168+/-36 and 93+/-28 IU, respectively. Protopine caused prolongation (P<0.05) in pentobarbital (55 mg kg-1)-induced sleep as well as potentiated strychnine-induced toxicity in rats, suggestive of an inhibitory effect on MDME. These results indicate that protopine exhibits anti-hepatotoxic action which may be mediated through inhibition of MDME. Copyright 1998 The Italian Pharmacological Society

Sensory fibers containing vanilloid receptor-1 (VR-1) mediate spinal cord stimulation-induced vasodilation.

PubMed

Wu, Mingyuan; Komori, Naoka; Qin, Chao; Farber, Jay P; Linderoth, Bengt; Foreman, Robert D

2006-08-30

Spinal cord stimulation (SCS) is used to improve peripheral blood flow in selected populations of patients with ischemia of the extremities. Previous studies show that antidromic activation of sensory fibers is an important mechanism that contributes to SCS-induced vasodilation. However, the characteristics of sensory fibers involved in vasodilation are not fully known. This study investigated the contribution of vanilloid receptor type 1 (VR-1) containing fibers to SCS-induced vasodilation. A unipolar ball electrode was placed on the left dorsal column at the lumbar 2-3 spinal cord segments (L2-L3) in sodium pentobarbital anesthetized, paralyzed and ventilated rats. Cutaneous blood flows from both ipsilateral (left) and contralateral (right) hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS (50 Hz; 0.2 ms) was applied through the ball electrode at 30%, 60%, 90% and 300% of motor threshold (MT). Resiniferatoxin (RTX), an ultra potent analog of capsaicin and VR-1 receptor agonist, was used to suppress the activities of VR-1 containing sensory fibers. SCS at 30%, 60%, 90% and also at 300% of MT significantly increased cutaneous blood flow in the ipsilateral foot pad compared to that in the contralateral side. RTX (2 microg/kg, i.v.) significantly attenuated SCS-induced vasodilation of the ipsilateral side (P<0.05, n=7) compared with responses prior to RTX administration. A pledget of cotton soaked with RTX (2 microg/ml) placed on L2-L3 spinal cord significantly decreased SCS-induced vasodilation of the ipsilateral side at 30%, 60%, 90% and 300% of MT (P<0.05, n=7) compared with responses prior to RTX administration. Additionally, topical application of a pledget of cotton soaked with RTX (2 microg/ml) on the sciatic nerve at the middle level of the thigh or on the tibial nerve at the lower level of the lower hindlimb also decreased SCS-induced vasodilation (n=5). SCS-induced vasodilation is predominantly mediated via VR-1 containing sensory

Hypnoanalgesia and the study of pain experience: from Cajal to modern neuroscience

PubMed Central

Lanfranco, Renzo C.; Canales-Johnson, Andrés; Huepe, David

2014-01-01

Santiago Ramón y Cajal (1852–1934) did not only contribute to neurobiology and neurohistology. At the end of the 19th century, he published one of the first clinical reports on the employment of hypnotic suggestion to induce analgesia (hypnoanalgesia) in order to relieve pain in childbirth. Today, the clinical application of hypnoanalgesia is considered an effective technique for the treatment of pain in medicine, dentistry, and psychology. However, the knowledge we have today on the neural and cognitive underpinnings of hypnotic suggestion has increased dramatically since Cajal’s times. Here we review the main contributions of Cajal to hypnoanalgesia and the current knowledge we have about hypnoanalgesia from neural and cognitive perspectives. PMID:25324822

Daily isoflurane exposure increases barbiturate insensitivity in medullary respiratory and cortical neurons via expression of ε-subunit containing GABA ARs.

PubMed

Hengen, Keith B; Nelson, Nathan R; Stang, Kyle M; Johnson, Stephen M; Smith, Stephanie M; Watters, Jyoti J; Mitchell, Gordon S; Behan, Mary

2015-01-01

The parameters governing GABAA receptor subtype expression patterns are not well understood, although significant shifts in subunit expression may support key physiological events. For example, the respiratory control network in pregnant rats becomes relatively insensitive to barbiturates due to increased expression of ε-subunit-containing GABAARs in the ventral respiratory column. We hypothesized that this plasticity may be a compensatory response to a chronic increase in inhibitory tone caused by increased central neurosteroid levels. Thus, we tested whether increased inhibitory tone was sufficient to induce ε-subunit upregulation on respiratory and cortical neurons in adult rats. Chronic intermittent increases in inhibitory tone in male and female rats was induced via daily 5-min exposures to 3% isoflurane. After 7d of treatment, phrenic burst frequency was less sensitive to barbiturate in isoflurane-treated male and female rats in vivo. Neurons in the ventral respiratory group and cortex were less sensitive to pentobarbital in vitro following 7d and 30d of intermittent isoflurane-exposure in both male and female rats. The pentobarbital insensitivity in 7d isoflurane-treated rats was reversible after another 7d. We hypothesize that increased inhibitory tone in the respiratory control network and cortex causes a compensatory increase in ε-subunit-containing GABAARs.

Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats.

PubMed

Abdolmaleki, Arash; Moghimi, Ali; Ghayour, Mohammad B; Rassouli, Morteza B

2016-10-15

Citicoline (cytidine-5'-diphosphocholine) is a neuroprotective agent that is administered following ischemic and traumatic brain injuries. There is little information about the antiseizure and anxiolytic effects of citicoline, which are therefore addressed in the present study. For evaluating the anticonvulsant effect of citicoline in the pentylentetrazole seizure model, a single intraperitoneal dose of citicoline was administered at 50, 100 or 150mg/kg. Sedative and anxiolytic effects of citicoline were examined via elevated plus maze and pentobarbital induced sleep tests. Results show that citicoline at the doses of 100 and 150mg/kg significantly delayed the latent period compared with the control (P<0.05). Citicoline at the doses of 100 and 150mg/kg significantly decreased total locomotion compared with the control (P<0.05). Additionally, citicoline at the doses of 100 and 150mg/kg significantly increased both percentage of entry and time spent in the open arms in the elevated plus maze test (P<0.05). The pentobarbital induced sleep test showed that citicoline significantly reduced the latency to sleep (P<0.05). Our results suggest that acute administration of citicoline has anticonvulsant activity and sedative effect. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of endothelial nitric oxide synthase as a trigger and mediator of isoflurane-induced delayed preconditioning in rabbit myocardium.

PubMed

Chiari, Pascal C; Bienengraeber, Martin W; Weihrauch, Dorothee; Krolikowski, John G; Kersten, Judy R; Warltier, David C; Pagel, Paul S

2005-07-01

Isoflurane produces delayed preconditioning in vivo. The authors tested the hypothesis that endothelial, inducible, or neuronal nitric oxide synthase (NOS) is a trigger or mediator of this protective effect. In the absence or presence of exposure to isoflurane (1.0 minimum alveolar concentration) 24 h before experimentation, pentobarbital-anesthetized rabbits (n = 128) instrumented for hemodynamic measurement received 0.9% saline (control), the nonselective NOS inhibitor N-nitro-l-arginine methyl ester (10 mg/kg), one of two of the selective inducible NOS antagonists aminoguanidine (300 mg/kg) or 1400W (0.5 mg/kg), or the selective neuronal NOS inhibitor 7-nitroindazole (50 mg/kg) administered before exposure to isoflurane (trigger; day 1) or left anterior descending coronary artery occlusion (mediator; day 2). All rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Tissue samples for reverse-transcription polymerase chain reaction and immunohistochemistry were also obtained in the presence or absence of N-nitro-l-arginine methyl ester with or without isoflurane pretreatment. Isoflurane significantly (P < 0.05) reduced infarct size (23 +/- 5% [mean +/- SD] of the left ventricular area at risk; triphenyltetrazolium chloride staining) as compared with control (42 +/- 7%). N-nitro-l-arginine methyl ester administered before isoflurane or coronary occlusion abolished protection (49 +/- 7 and 43 +/- 10%, respectively). Aminoguanidine, 1400W, and 7-nitroindazole did not alter infarct size or affect isoflurane-induced delayed preconditioning. Isoflurane increased endothelial but not inducible NOS messenger RNA transcription and protein translation immediately and 24 h after administration of the volatile agent. Pretreatment with N-nitro-l-arginine methyl ester attenuated isoflurane-induced increases in endothelial NOS expression. The results suggest that endothelial NOS but not inducible or neuronal NOS is a trigger and mediator of delayed

A Study of Cross-Cultural Communication for U.S. Military Application: Identifying Mind/Minefields and Avenues of Approach

DTIC Science & Technology

2001-04-01

power to induce a powerful psychological reaction.101 Certain catchwords, slogans, and rallying cries have hypnotic power.102 When the meaning of...Douglas points out that that the shedding of blood for food and sexual fluids for reproduction are necessary to survival but as outside body fluids

The utility of bispectral index monitoring for prevention of rocuronium-induced withdrawal movement in children: A randomized controlled trial.

PubMed

Lim, Byung Gun; Lee, Il Ok; Kim, Young Sung; Won, Young Ju; Kim, Heezoo; Kong, Myoung Hoon

2017-01-01

This study was designed to determine whether a deep hypnotic state with a bispectral index (BIS) value less than 40 could alleviate withdrawal movement (WM) upon rocuronium injection during anesthesia induction in children. Finally, 135 healthy children (3-12 years) scheduled for minor elective surgery were studied. Without premedication, anesthesia was induced with thiopental sodium 5 mg/kg. Patients were randomized into 2 groups (control vs experimental) and then by virtue of rocuronium injection time, patients in the experimental group were allocated into 2 groups, as follows: in the control group (group C; n = 45), rocuronium 0.6 mg/kg was administered at the loss of eyelash reflex; in the 1st experimental group, rocuronium 0.6 mg/kg was administered when BIS fell to less than 40 (group T; n = 45); however, if BIS did not fall below 40 after thiopental sodium administration, manual ventilation was provided with oxygen 6 L/minute using sevoflurane 8% and then rocuronium was administered when BIS fell below 40 (the 2nd experimental group, group S; n = 45). Rocuronium-induced WM was evaluated using a 4-point scale (no movement; movement/withdrawal involving the arm only; generalized response, with movement/withdrawal of more than 1 extremity, but no requirement for restraint of the body; and generalized response which required restraint of the body and caused coughing or breath-holding). No significant differences were found among the groups for patient characteristics including age, sex, height, and location of venous cannula. However, body weight, height, and body mass index in group S were all smaller than those in group T. The incidence of WM caused by rocuronium was 100% in group C, 95.6% in group T, and 80% in group S, and was significantly lower in group S than in group C. The grade of WM was 3.7 ± 0.6 in group C, 3.2 ± 0.9 in group T, and 2.6 ± 1.0 in group S. It was significantly lower in group T than in group C and

Improving Sedative-Hypnotic Prescribing in Older Hospitalized Patients: Provider-Perceived Benefits and Barriers of a Computer-Based Reminder

PubMed Central

Concato, John; Inouye, Sharon K.

2007-01-01

Background Older adults are commonly prescribed sedative-hypnotic (SH) medications when hospitalized, yet these drugs are associated with important adverse effects such as falls and delirium. Objective To identify provider-perceived benefits or barriers of a computer-based reminder regarding appropriate use of SH medications. Design Qualitative study using semi-structured interviews. Participants and setting Thirty-six house staff physicians at a university hospital. Measurements Information was collected regarding the experiences of prescribing an SH using a computer order entry system with a reminder intervention. Clinicians were asked about their perceptions of the reminder and what they found most and least useful about it. Responses were analyzed using grounded theory methodology. Results The 36 participants (including 29 interns) had prescribed an SH medication for a hospitalized patient over age 65 years. Three themes associated with benefits of a computer reminder were identified: increasing awareness of safety, including risk of delirium, falls, and general patient safety risks; usefulness of information technology; and the value of the educational content, including geriatric pharmacology review and nonpharmacologic treatment options. Barriers included the demands of the reminder with regard to time needed to read the reminder, the role of clinician experience with regard to preserving clinical autonomy, and the information content of the reminder, including its being too basic or not relevant for a particular patient. The mean satisfaction rating for the reminder was 8.5 (±0.9 SD), with 10 indicating high satisfaction. Conclusions Improving decision support systems involves an understanding of how clinicians respond to real-time strategies encouraging better prescribing. PMID:18095041

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm

PubMed Central

Licata, Stephanie C.; Nickerson, Lisa D.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

2013-01-01

Networks of brain regions having synchronized fluctuations of the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) time-series at rest, or “resting state networks” (RSNs), are emerging as a basis for understanding intrinsic brain activity. RSNs are topographically consistent with activity-related networks subserving sensory, motor, and cognitive processes, and studying their spontaneous fluctuations following acute drug challenge may provide a way to understand better the neuroanatomical substrates of drug action. The present within-subject double-blind study used BOLD fMRI at 3T to investigate the functional networks influenced by the non-benzodiazepine hypnotic zolpidem (Ambien®). Zolpidem is a positive modulator of γ-aminobutyric acidA (GABAA) receptors, and engenders sedative effects that may be explained in part by how it modulates intrinsic brain activity. Healthy participants (n= 12) underwent fMRI scanning 45 min after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured while participants gazed at a static fixation point (i.e., at rest). Data were analyzed using group independent component analysis (ICA) with dual regression and results indicated that compared to placebo, the highest dose of zolpidem increased functional connectivity within a number of sensory, motor, and limbic networks. These results are consistent with previous studies showing an increase in functional connectivity at rest following administration of the positive GABAA receptor modulators midazolam and alcohol, and suggest that investigating how zolpidem modulates intrinsic brain activity may have implications for understanding the etiology of its powerful sedative effects. PMID:23296183

The Uses of Hypnotherapy with Learning Disabled Children.

ERIC Educational Resources Information Center

Johnson, Lynn S.; And Others

1981-01-01

Explored the impact of group hypnotic and self-hypnotic training on the academic performance and self-esteem of learning disabled (LD) children. Important predictors of self-esteem improvement were the child's hypnotic susceptibility score and self-hypnotic practice by children and parents. Hypnotherapy is of potential benefit to self-esteem…

Pharmacological and toxicological study of a chemical-standardized ethanol extract of the branches and leaves from Eysenhardtia polystachya (Ortega) Sarg. (Fabaceae).

PubMed

Alonso-Castro, Angel Josabad; Zapata-Morales, Juan Ramón; Arana-Argáez, Victor; Torres-Romero, Julio Cesar; Ramírez-Villanueva, Eyra; Pérez-Medina, Sabino Eduardo; Ramírez-Morales, Marco Antonio; Juárez-Méndez, Mario Alberto; Infante-Barrios, Yessica Paola; Martínez-Gutiérrez, Fidel; Carranza-Álvarez, Candy; Isiordia-Espinoza, Mario Alberto; Flores-Santos, Andrés

2018-06-18

Eysenhardtia polystachya is used for the empirical treatment of cancer, infections, diarrhea, inflammation, and pain. This study identified, using GC-MS, the main chemical components in an ethanol extract of E. polystachya branches and leaves (EPE) and tested its cytotoxic, antimicrobial, anti-diarrheal, anti-inflammatory, and antinociceptive effects. The in vitro and in vivo toxicity of EPE was evaluated using the comet assay in human peripheral blood mononuclear cells (PBMC) and the acute toxicity test in mice, respectively. The cytotoxic and the antimicrobial effects were performed using the MTT assay and the minimum inhibitory concentration (MIC) test, respectively. The levels of pro-inflammatory mediators in LPS-stimulated macrophages were measured to evaluate the in vitro anti-inflammatory effects of EPE. The antidiarrheal (castor oil test, small intestine transit, and castor oil-induced enteropooling), and anti-inflammatory activities (TPA and carrageenan) of EPE were also performed. The antinociceptive actions of EPE were carried out with the following tests: acetic acid, formalin, and hot plate. The hypnotic and locomotor effects were analyzed using pentobarbital and a rotarod system, respectively. The main component in EPE was D-pinitol (26.93%). The antidiarrheal and antinociceptive effects of D-pinitol were also evaluated. EPE showed low in vitro toxicity (DNA damage in PBMC at concentrations higher than 200 µg/ml), and low in vivo toxicity (LD 50 > 2000 mg/kg i.p. and p.o.). Furthermore, EPE lacked cytotoxic activity (IC 50 > 300 µg/ml) on human cancer cells, but showed good antimicrobial effects in E. coli (MIC=1.56 µg/ml) and S. aureus (MIC = 0.78 µg/ml). In multi-drug resistant microorganisms, EPE showed MIC> 100 µg/ml. EPE exerted in vitro anti-inflammatory effects, mainly, by the decrease in the production of H 2 O 2 (IC 50 = 43.9 ± 3.8 µg/ml), and IL-6 (73.3 ± 6.9 µg/ml). EPE (ED 50 =7.5 ± 0.9�

Group Hypnotherapy With Learning Disabled Children.

ERIC Educational Resources Information Center

Johnson, Lynn S.; And Others

The impact of group hypnotic and self-hypnotic training on the academic performance and self-esteem of learning disabled children was explored. Three hypnotic training sessions and instructions for six weeks of daily self-hypnotic practice containing suggestions for imagery related to improvement in these areas were given to 15 children, their…

Isoflurane: An Ideal Anesthetic for Rodent Orthotopic Liver Transplantation Surgery?

PubMed

Cao, D; Liu, Y; Li, J; Gong, J

2016-10-01

Because the choice of anesthetic affects the rodent orthotopic liver transplantation (OLT) model, we compared the effects of isoflurane, ketamine, chloral hydrate, and pentobarbital on the OLT model. OLT was performed using the two-cuff technique. Two hundred male rats were randomly divided into five groups: control, isoflurane, ketamine, chloral hydrate, and pentobarbital groups. Rectal temperatures, respiratory rates, arterial blood values (pH, PaCO 2 , PaO 2 , and SatO 2 ), liver function tests and histopathology, recovery times, and anhepatic stage mortality rates were assessed. Compared with controls, respiratory rates decreased by 20% in the isoflurane group, and decreased by 40%-50% in the ketamine, chloral hydrate, and pentobarbital groups. The PaO 2 , SatO 2 , and pH levels in the ketamine, chloral hydrate, and pentobarbital groups were significantly lower than those in the isoflurane and control groups (P < .05). Only the pentobarbital group displayed significant liver histopathologic changes along with significantly higher levels of serum alanine aminotransferase and total bilirubin, but a significantly lower level of serum albumin, compared with the control group (P < .05). The isoflurane group had a 0% anhepatic stage mortality rate compared with rates of 30%-40% in the other anesthetic groups. Isoflurane should be the preferred anesthetic for rodent OLT surgery due to its minimal respiratory and hepatic physiological effects as well as its low anhepatic phase mortality rate. Secondary to isoflurane, ketamine and chloral hydrate may be administered as donor anesthetics. Pentobarbital use should be avoided entirely in rodent OLT surgery due to its significant hepatotoxic effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychedelic drugs, hippie counterculture, speed and phenobarbital treatment of sedative-hypnotic dependence: a journey to the Haight Ashbury in the Sixties.

PubMed

Wesson, Donald R

2011-01-01

The 1960s were a time of social upheaval, wars, vibrant creativity and missed opportunity. Mainstream culture and a psychedelic drug-using counterculture shared a belief in "better living through chemistry'," but they disagreed about the particular chemistry. The Vietnam war and the cold war with the Soviet Union, racial discrimination, and gender roles fueled political activism. "Yes we can" was not a slogan of the time but political activists clearly believed they could change the beliefs, attitudes and behavior of mainstream culture; and they did. Hippie counterculture on the other hand was largely alienated and strove primarily to develop a separate culture with its own mores, beliefs and lifestyles. Although there was some overlap between hippies and activists, hippies didn't generally have the same sense of political empowerment. Hippie enclaves developed in New York; Boston; Seattle; Austin, Texas and elsewhere; but the epicenter was arguably the Haight-Asbury District of San Francisco. Psychedelic drugs, marijuana and the Vietnam war were among many wedge issues. This paper conjures up a personal history related to the evolution of the hippie counterculture, changing drug use patterns in the Haight-Ashbury, and the origins of a technique of withdrawing patients from barbiturates and other sedative-hypnotics using phenobarbital variously known as the "Phenobarbital Withdrawal Protocol, or the "Smith and Wesson Protocol."

Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT.

PubMed

Jubair, Shaiban; Li, Jianping; Dehlin, Heather M; Manteufel, Edward J; Goldspink, Paul H; Levick, Scott P; Janicki, Joseph S

2015-08-15

Accumulating evidence indicates that substance P is cardioprotective following ischemia-reperfusion primarily due to its potent coronary vasodilator actions. However, an anti-apoptotic effect of substance P has been observed in tenocytes following ischemia, which involved activation of the AKT pathway. This suggests the possibility that substance P also provides cardioprotection via direct actions to activate AKT in myocardial cells. The purpose of this study was to test the hypothesis that substance P attenuates ischemia-related cell death via direct effects on myocardial cells by activating cell survival pathways. Seven-week-old male Sprague-Dawley rats, anesthetized with intraperitoneal pentobarbital sodium (100 mg/kg), were used. The ability of substance P to prevent cellular damage was assessed following ischemia-reperfusion in an isolated heart preparation and in short-term hypoxia without reperfusion using a left ventricular tissue slice culture preparation. In addition, the NK-1 receptor and AKT involvement was assessed using the NK-1 receptor antagonist L732138 and the AKT inhibitor LY294002. The results indicate that substance P reduced the ischemia-related release of lactate dehydrogenase in both preparations and the degree of apoptosis and necrosis in the hypoxic left ventricular slices, indicating its ability to attenuate cell damage; and induced AKT phosphorylation, with both the AKT inhibitor and NK-1 receptor antagonist preventing the increased phosphorylation of AKT and the ability of substance P to attenuate hypoxic cellular damage. It is concluded that substance P reduces ischemia/hypoxia-induced myocardial cell death by acting directly on cardiac cells to initiate cell survival pathways via the NK-1 receptor and AKT. Copyright © 2015 the American Physiological Society.

Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT

PubMed Central

Jubair, Shaiban; Li, Jianping; Dehlin, Heather M.; Manteufel, Edward J.; Goldspink, Paul H.; Levick, Scott P.

2015-01-01

Accumulating evidence indicates that substance P is cardioprotective following ischemia-reperfusion primarily due to its potent coronary vasodilator actions. However, an anti-apoptotic effect of substance P has been observed in tenocytes following ischemia, which involved activation of the AKT pathway. This suggests the possibility that substance P also provides cardioprotection via direct actions to activate AKT in myocardial cells. The purpose of this study was to test the hypothesis that substance P attenuates ischemia-related cell death via direct effects on myocardial cells by activating cell survival pathways. Seven-week-old male Sprague-Dawley rats, anesthetized with intraperitoneal pentobarbital sodium (100 mg/kg), were used. The ability of substance P to prevent cellular damage was assessed following ischemia-reperfusion in an isolated heart preparation and in short-term hypoxia without reperfusion using a left ventricular tissue slice culture preparation. In addition, the NK-1 receptor and AKT involvement was assessed using the NK-1 receptor antagonist L732138 and the AKT inhibitor LY294002. The results indicate that substance P reduced the ischemia-related release of lactate dehydrogenase in both preparations and the degree of apoptosis and necrosis in the hypoxic left ventricular slices, indicating its ability to attenuate cell damage; and induced AKT phosphorylation, with both the AKT inhibitor and NK-1 receptor antagonist preventing the increased phosphorylation of AKT and the ability of substance P to attenuate hypoxic cellular damage. It is concluded that substance P reduces ischemia/hypoxia-induced myocardial cell death by acting directly on cardiac cells to initiate cell survival pathways via the NK-1 receptor and AKT. PMID:26071541

Use of the EMPOWER brochure to deprescribe sedative-hypnotic drugs in older adults with mild cognitive impairment.

PubMed

Martin, Philippe; Tannenbaum, Cara

2017-01-31

Evidence-based mailed educational brochures about the harms of sedative-hypnotic use lead to discontinuation of chronic benzodiazepine use in older adults. It remains unknown whether patients with mild cognitive impairment (MCI) are able to understand the information in the EMPOWER brochures, and whether they achieve similar rates of benzodiazepine discontinuation. Post-hoc analysis of the EMPOWER randomized, double-blind, wait-list controlled trial that assessed the effect of a direct-to-consumer educational intervention on benzodiazepine discontinuation. 303 community-dwelling chronic users of benzodiazepine medication aged 65-95 years were recruited from general community pharmacies in the original trial, 261 (86%) of which completed the trial extension phase. All participants of the control arm received the EMPOWER brochure during the trial extension. Normal cognition (n = 139) or MCI (n = 122) was determined during baseline cognitive testing using the Montreal Cognitive Assessment questionnaire. Changes in knowledge pre- and post-intervention were assessed with a knowledge questionnaire and changes in beliefs were calculated using the Beliefs about Medicines Questionnaire. Logistic regression was used to compare knowledge gained, change in beliefs and benzodiazepine cessation rates between participants with and without MCI. Complete discontinuation of benzodiazepines was achieved in 39 (32.0% [24.4,40.7]) participants with MCI and in 53 (38.1% [30.5,46.4]) with normal cognition (adjusted OR 0.79, 95% CI [0.45-1.38]). Compared to individuals with normal cognition, MCI had no effect on the acquisition of new knowledge, change in beliefs about benzodiazepines or elicitation of cognitive dissonance. The EMPOWER brochure is effective for reducing benzodiazepines in community-dwelling older adults with mild cognitive impairment. Our ClinicalTrials.gov identifier is NCT01148186 , June 21 st 2010.

The powers of suggestion: Albert Moll and the debate on hypnosis.

PubMed

Maehle, Andreas-Holger

2014-03-01

The Berlin physician Albert Moll (1862-1939) was an advocate of hypnotic suggestion therapy and a prolific contributor to the medical, legal and public discussions on hypnotism from the 1880s to the 1920s. While his work in other areas, such as sexology, medical ethics and parapsychology, has recently attracted scholarly attention, this paper for the first time comprehensively examines Moll's numerous publications on hypnotism and places them in their contemporary context. It covers controversies over the therapeutic application of hypnosis, the reception of Moll's monograph Der Hypnotismus (1889), his research on the rapport between hypnotizer and subject, his role as an expert on 'hypnotic crime', and his views on the historical influence of hypnotism on the development of psychotherapy. My findings suggest that Moll rose to prominence due to the strong late-nineteenth-century public and medical interest in the phenomena of hypnosis, but that his work was soon overshadowed by new, non-hypnotic psychotherapeutic approaches, particularly Freud's psychoanalysis.

Effects of Amphetamine-CNS Depressant Combinations and of Other CNS Stimulants in Four-Choice Drug Discriminations

ERIC Educational Resources Information Center

Li, Mi; Wessinger, William D.; McMillan, D. E.

2005-01-01

Three pigeons were trained to discriminate among 5 mg/kg pentobarbital, 2 mg/kg amphetamine, a combination of these two drugs at these doses, and saline using a four-choice procedure (amphetamine--pentobarbital group). Three other pigeons were trained to discriminate among 5 mg/kg morphine, 2 mg/kg methamphetamine, a combination of these two drugs…

Contextual and Temporal Disorganization During Posthypnotic Amnesia.

ERIC Educational Resources Information Center

Evans, Frederick J.; Kihlstrom, John F.

This paper discusses work on hypnotic amnesia as a paradigm of laboratory induced state-specific memory. Earlier research on sleep-specific learning and learning in varied states of consciousness is reviewed. Posthypnotic amnesia is viewed as an effective method of studying state-specific recall of episodic experiences. It is noted that highly…

Interaction of secalonic acid D with phenobarbital, 3-methyl cholanthrene, and SKF-525A in mice.

PubMed

Reddy, C S; Reddy, R V; Hayes, A W

1983-01-01

Secalonic acid D (SAD) is an acutely toxic and teratogenic fungal metabolite produced by Penicillium oxalium in corn and other cereal grains. Experiments were conducted to study the effects of single and multiple doses of SAD on pentobarbital-induced narcosis, as an index of the modulating effect of SAD on the hepatic drug metabolizing enzymes in mice. The effects of known enzyme modulators-phenobarbital (PB), 3-methyl cholanthrene (3-MC), and diethylaminoethyl diphenylproply acetate hydrochloride (SKF-525A)-on the acute toxicity of SAD in mice were also studied using body weights, mortality, and histopathology as indices. Results of this study failed to demonstrate any modulating effect by SAD of pentobarbital metabolizing enzymes. Pretreatment with SKF-525A, an enzyme inhibitor, enhanced SAD toxicity in mice, whereas pretreatment with PB or 3-MC, known enzyme inducers, had no effect. Further studies of interaction of [14C]SAD with PB and SKF-525A revealed that although neither PB nor SKF-525A altered the ratio of parent compound to total metabolites excreted in bile, SKF-525A significantly reduced the bile flow as well as the elimination of SAD-derived radioactivity in bile. These results strongly suggest the possibility that the effects of SKF-525A, other than the enzyme inhibition, may be responsible for its enhancement of SAD toxicity in mice.

Exposure to reactive intermediate-inducing drugs during pregnancy and the incident use of psychotropic medications among children.

PubMed

Tran, Yen-Hao; Groen, Henk; Bergman, Jorieke E H; Hak, Eelko; Wilffert, Bob

2017-03-01

Our study aimed to investigate the association between prenatal exposure to reactive intermediate (RI)-inducing drugs and the initiation of psychotropic medications among children. We designed a cohort study using a pharmacy prescription database. Pregnant women were considered exposed when they received a prescription of RI-inducing drugs. These drugs could be either used alone (RI+/FAA-) or combined with drugs exhibiting folic acid antagonism (FAA, RI+/FAA+). The reference group included pregnant women who did not receive any RI-inducing drugs or FAA drugs. We analyzed 4116 exposed and 30 422 reference pregnancies. The hazard ratio (HR) with 95% confidence interval (CI) was 1.27 (95%CI 1.15-1.41) for pregnancies exposed to RI-inducing drugs as a whole. Considering subgroups of RI-inducing drugs, prenatal exposure to both RI+/FAA+ and RI+/FAA- was associated with the children's initiation of psychotropic medications, HRs being 1.35 (95%CI 1.10-1.66) and 1.26 (1.13-1.41), respectively. The HRs were increased with prolonged exposure to RI-inducing drugs, especially in the first and second trimesters. In a detailed examination of the psychotropics, the incidences of receiving antimigraine preparations and psychostimulants were significantly increased for the exposed children, compared with the reference children. The incidences of receiving antipsychotics and hypnotics were also higher for the exposed children; however, the HRs did not reach significance after adjustment. We found a significantly increased incident use of psychotropic medications among children prenatally exposed to RI-inducing drugs, especially during the first and second trimesters. This suggests a detrimental effect during critical periods of brain development. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006.

PubMed

Gissler, Mika; Artama, Miia; Ritvanen, Annukka; Wahlbeck, Kristian

2010-06-30

Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results. The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons) in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or an induced abortion. In total 2.1% of women with a birth and 5.1% of women with an induced abortion had used a psychotropic medicine 0-3 months before pregnancy. Psychotropic drug users terminated their pregnancies (30.9%) more often than other pregnant women (15.5%). Adjustment for background characteristics explained one third of this elevated risk, but the risk remained significantly increased among users of psychotropic medicine (OR 1.94, 95% confidence intervals 1.87-2.02). A similar risk was found for first pregnancies (30.1% vs. 18.9%; adjusted OR 1.53, 95% confidence intervals 1.42-1.65). The rate for terminating pregnancy was the highest for women using hypnotics and sedatives (35.6% for all pregnancies and 29.1% for first pregnancies), followed by antipsychotics (33.9% and 36.0%) and antidepressants (32.0% and 32.1%). The observed increased risk for induced abortion among women with psychotropic medication highlights the importance to acknowledge the mental health needs of women seeking an induced abortion. Further studies are needed to establish the impact of pre-existing differences in mental health on mental health outcomes of induced abortions compared to outcomes of pregnancies ending in a birth.

The powers of suggestion: Albert Moll and the debate on hypnosis

PubMed Central

Maehle, Andreas-Holger

2014-01-01

The Berlin physician Albert Moll (1862–1939) was an advocate of hypnotic suggestion therapy and a prolific contributor to the medical, legal and public discussions on hypnotism from the 1880s to the 1920s. While his work in other areas, such as sexology, medical ethics and parapsychology, has recently attracted scholarly attention, this paper for the first time comprehensively examines Moll’s numerous publications on hypnotism and places them in their contemporary context. It covers controversies over the therapeutic application of hypnosis, the reception of Moll’s monograph Der Hypnotismus (1889), his research on the rapport between hypnotizer and subject, his role as an expert on ‘hypnotic crime’, and his views on the historical influence of hypnotism on the development of psychotherapy. My findings suggest that Moll rose to prominence due to the strong late-nineteenth-century public and medical interest in the phenomena of hypnosis, but that his work was soon overshadowed by new, non-hypnotic psychotherapeutic approaches, particularly Freud’s psychoanalysis. PMID:24594818

Hypnosis as sole anaesthesia for skin tumour removal in a patient with multiple chemical sensitivity.

PubMed

Facco, E; Pasquali, S; Zanette, G; Casiglia, E

2013-09-01

A female patient with multiple chemical sensitivity and previous anaphylactoid reactions to local anaesthetics was admitted for removal of a thigh skin tumour under hypnosis as sole anaesthesia. The hypnotic protocol included hypnotic focused analgesia and a pre-operative pain threshold test. After inducing hypnosis, a wide excision was performed, preserving the deep fascia, and the tumour was removed; the patient's heart rate and blood pressure did not increase during the procedure. When the patient was de-hypnotised, she reported no pain and was discharged immediately. Our case confirms the efficacy of hypnosis and demonstrates that it may be valuable as a sole anaesthetic method in selected cases. Hypnosis can prevent pain perception and surgical stress as a whole, comparing well with anaesthetic drugs. © 2013 The Association of Anaesthetists of Great Britain and Ireland.

Measurement of mean circulatory filling pressure and vascular compliance in domestic pigs.

PubMed

Ogilvie, R I; Zborowska-Sluis, D; Tenaschuk, B

1990-06-01

To measure mean circulatory filling pressure (Pmcf), a balloon was placed in the right atrium of seven pentobarbital sodium-anesthetized open-chest pigs for transient occlusion of flow combined with mechanical transfer of blood from the arterial to the venous circulation. Equilibration occurred within 6-8 s at a pressure at 12.3 +/- 0.3 (SE) mmHg after a 2.9 +/- 0.2 ml/kg transfer of blood. In another group of pentobarbital sodium-anesthetized closed-chest pigs, acetylcholine (ACh) was used to induce cardiac arrest. The Pmcf was 11.6 +/- 1.0 mmHg in the 7:17 pigs that arrested for 6-8 s. In four isoflurane-anesthetized closed-chest pigs, the Pmcf was 12.0 +/- 1.0 mmHg after terminal cardiac arrest induced by KCl. The pressure gradient for venous return [Pmcf--right atrial pressure (Pra)] averaged 5.9 +/- 0.2 mmHg. Total vascular compliance estimated from plots of Pmcf at base line, 5, and 10 ml/kg increases in circulating volume was 2.1 +/- 0.3 and 3.5 +/- 0.9 ml.kg-1.mmHg-1 in the balloon and ACh groups, respectively compared with 2.8 +/- 0.4 ml.kg-1.mmHg-1 using a volume infusion-withdrawal method without circulatory arrest. The use of ACh for the estimate of Pmcf in the pig is not recommended because of failure to consistently induce circulatory arrest and probable failure to achieve sufficient equilibrium of vascular pressures 6-8 s postarrest when it occurs.

Main neuroendocrine features and therapy in primary sleep troubles.

PubMed

Amihăesei, Ioana Cristina; Mungiu, O C

2012-01-01

Insomnia is a sleep trouble in which the patient has difficulties in falling or in staying asleep. There are patients who fall asleep easily, but wake up too early; others have troubles in falling asleep and a third category has troubles with both falling and staying asleep. Independent of the type of insomnia, the final result is a poor-quality sleep, responsible for depressive or irritable mood, loss in concentration, learning and memory capacities. Sleep is essential to emotional and physical health. Inadequate sleep over a period of time is increasing the risks for obesity, diabetes, heart disease and depression. People suffering of chronic insomnia show an increased predisposition for psychiatric problems. People who had sleep troubles reported impaired ability to fulfill tasks involving memory, learning, logical reasoning and mathematical operations. New studies show that insomnia might be a result of the decrease of gamma-aminobutyric acid (GABA), a neurochemical responsible for the decrease of activity in many brain areas. Lower brain GABA levels were also found in people with major depressive disorder and anxiety disorders. Hypnotics, such as benzodiazepines are acting increasing the activity of the GABA neurons. Exposure to stress is associated with a greater risk for insomnia, with individual differences. Stress activates the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. Increased activity of HPA axis is stimulating the secretion of corticotropin-releasing hormone, further inducing sleep disruption. Insomnia is also associated with depression and anxiety disorders, in which the HPA axis is characteristically overactive. People who show predisposition to sleep troubles have a hyperactive sympathetic nervous system, they are usually suffering from hyperarousal and they have a more intense response to stressful events. Primary sleep troubles (insomnia) has no apparent causes, is lasting more than one month, and is affecting

Targeted deletion of the GABRA2 gene encoding alpha2-subunits of GABA(A) receptors facilitates performance of a conditioned emotional response, and abolishes anxiolytic effects of benzodiazepines and barbiturates.

PubMed

Dixon, C I; Rosahl, T W; Stephens, D N

2008-07-01

Mice with point-mutated alpha2 GABA(A) receptor subunits (rendering them diazepam insensitive) are resistant to the anxiolytic-like effects of benzodiazepines (BZs) in the conditioned emotional response (CER) test, but show normal anxiolytic effects of a barbiturate. We investigated the consequence of deleting the alpha2-subunit on acquisition of the CER with increasing intensity of footshock, and on the anxiolytic efficacy of a benzodiazepine, diazepam, and a barbiturate, pentobarbital. alpha2 knockout (KO) and wildtype (WT) mice were trained in a conditioned emotional response (CER) task, in which lever pressing for food on a variable interval (VI) schedule was suppressed during the presentation of a compound light/tone conditioned stimulus (CS+) that predicted footshock. The ability of diazepam and of pentobarbital to reduce suppression during the CS+ was interpreted as an anxiolytic response. There were no differences between the genotypes in shock sensitivity, as assessed by their flinch responses to increasing levels of shock. However, alpha2 KO mice showed a greater suppression of lever pressing than WT littermates in the presence of a compound cue signalling footshock. Diazepam (0, 0.5, 1 and 2 mg/kg) induced a dose-dependent anxiolytic-like effect in WT mice but no such effect was seen in KO mice. Similarly, although pentobarbital (20 mg/kg) reduced the ability of the CS+ to reduce lever pressing rates in WT mice, this effect was not seen in the KO. These findings suggest that alpha2-containing GABA(A) receptors mediate the anxiolytic effects of barbiturates, as well as benzodiazepines, and that they may be involved in neuronal circuits underlying conditioned anxiety.

Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder.

PubMed

Ouchi, Hirofumi; Ono, Kazuya; Murakami, Yukihisa; Matsumoto, Kinzo

2013-02-01

Social isolation of rodents (SI) elicits a variety of stress responses such as increased aggressiveness, hyper-locomotion, and reduced susceptibility to pentobarbital. To obtain a better understanding of the relevance of SI-induced behavioral abnormalities to psychiatric disorders, we examined the effect of SI on latent learning as an index of spatial attention, and discussed the availability of SI as an epigenetic model of attention deficit hyperactivity disorder (ADHD). Except in specially stated cases, 4-week-old male mice were housed in a group or socially isolated for 3-70 days before experiments. The animals socially isolated for 1 week or more exhibited spatial attention deficit in the water-finding test. Re-socialized rearing for 5 weeks after 1-week SI failed to attenuate the spatial attention deficit. The effect of SI on spatial attention showed no gender difference or correlation with increased aggressive behavior. Moreover, SI had no effect on cognitive performance elucidated in a modified Y-maze or an object recognition test, but it significantly impaired contextual and conditional fear memory elucidated in the fear-conditioning test. Drugs used for ADHD therapy, methylphenidate (1-10 mg/kg, i.p.) and caffeine (0.5-1 mg/kg, i.p.), improved SI-induced latent learning deficit in a manner reversible with cholinergic but not dopaminergic antagonists. Considering the behavioral features of SI mice together with their susceptibility to ADHD drugs, the present findings suggest that SI provides an epigenetic animal model of ADHD and that central cholinergic systems play a role in the effect of methylphenidate on SI-induced spatial attention deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

Annual Research Progress Report (William Beaumont Army Medical Center) FY 1983

DTIC Science & Technology

1994-03-23

Algeo, Dept of Radiology) .............................................. 58 Pacheco, EJ: 93/53 (0) Phase II Study of Interferon-Modulated Indium- Il 1 ...76 Lutz, P: 92/68 ( 1 ) Nursing Effects on Mastectomy Patients’ Perception of Self Esteem ............................ 77 Nufer, E: 93/08 (C) Cardiac...15 1 Kravitz, MB: 93/49 (0) A Comparison Study of Midazolam and Pentobarbital Versus Pentobarbital A),=e in the Effective Sedation of

Hypnosis as a Tool in Parapsychological Research.

ERIC Educational Resources Information Center

Casler, Lawrence

The existence of extrasensory perception (ESP) among volunteer college students was investigated in numerous studies, under hypnotic and non-hypnotic conditions. Study results indicate that: (1) some types of suggestions administered in a hypnotic context appear to facilitate extrasensory perception; (2) strong ESP suggestions administered without…

Hypnosis as obedience behaviour.

PubMed

Hunt, S M

1979-02-01

Obedience to authority has been implicated in hypnotic behaviour from the earliest theories. However, no exact formulation of a model of obedience was available until Milgram's experiments in the 1960s. Milgram's model can usefully be applied to hypnotic behaviour in terms of antecedent and immediate antecedent variables, binding and strain factors and the resolution of conflict. An experiment was carried out to test the hypothesis that the presence of a 'disobedient' hypnotic subject in the same room as another hypnotic subject would lower the susceptibility to hypnosis of the second subject. Results showed that when one subject disobeyed by leaving the hypnotic situation, susceptibility was significantly less than that of control subjects. It is suggested that hypnosis can be viewed as an 'agentic state' whereby the subject gives up autonomy and relinquishes responsibility for his actions to the hypnotist, whilst remaining responsible to the hypnotist for his performance as an hypnotic subject.

Levo-tetrahydropalmatine inhibits the acquisition of ketamine-induced conditioned place preference by regulating the expression of ERK and CREB phosphorylation in rats.

PubMed

Du, Yan; Du, Li; Cao, Jie; Hölscher, Christian; Feng, Yongming; Su, Hongliang; Wang, Yujin; Yun, Ke-Ming

2017-01-15

Levo-tetrahydropalmatine (l-THP) is an alkaloid purified from the Chinese herbs Corydalis and Stephania and has been used in many traditional Chinese herbal preparations for its sedative, analgesic and hypnotic properties. Previous studies demonstrated that l-THP has antagonistic activity on dopamine receptors; thus, it may have potential therapeutic effects on drug abuse. However, whether l-THP affects ketamine-induced conditioned place preference (CPP) remains unclear. Therefore, the present study was designed to evaluate the effects of l-THP on the rewarding behavior of ketamine through CPP. Results revealed that ketamine (5, 10 and 15mg/kg) induced CPP in rats. Furthermore, Ketamine (10mg/kg) promoted the phosphorylation of extracellular-regulated kinase (ERK) and cAMP responsive element binding protein (CREB) in the hippocampus (Hip) and caudate putamen (CPu), but not in the prefrontal cortex (PFc). l-THP (20mg/kg) co-administered with ketamine during conditioning inhibited the acquisition of ketamine-induced CPP in rats. Furthermore, l-THP (20mg/kg) prevented the enhanced phosphorylation of ERK and CREB in CPu and Hip. These results suggest that l-THP has potential therapeutic effects on ketamine-induced CPP. The underlying molecular mechanism may be related to its inhibitory effect on ERK and CREB phosphorylation in Hip and CPu. The present data supports the potential use of l-THP for the treatment of ketamine addiction. Copyright © 2016 Elsevier B.V. All rights reserved.

Placebo-suggestion modulates conflict resolution in the Stroop Task.

PubMed

Magalhães De Saldanha da Gama, Pedro A; Slama, Hichem; Caspar, Emilie A; Gevers, Wim; Cleeremans, Axel

2013-01-01

Here, we ask whether placebo-suggestion (without any form of hypnotic induction) can modulate the resolution of cognitive conflict. Naïve participants performed a Stroop Task while wearing an EEG cap described as a "brain wave" machine. In Experiment 1, participants were made to believe that the EEG cap would either enhance or decrease their color perception and performance on the Stroop task. In Experiment 2, participants were explicitly asked to imagine that their color perception and performance would be enhanced or decreased (non-hypnotic imaginative suggestion). We observed effects of placebo-suggestion on Stroop interference on accuracy: interference was decreased with positive suggestion and increased with negative suggestion compared to baseline. Intra-individual variability was also increased under negative suggestion compared to baseline. Compliance with the instruction to imagine a modulation of performance, on the other hand, did not influence accuracy and only had a negative impact on response latencies and on intra-individual variability, especially in the congruent condition of the Stroop Task. Taken together, these results demonstrate that expectations induced by a placebo-suggestion can modulate our ability to resolve cognitive conflict, either facilitating or impairing response accuracy depending on the suggestion's contents. Our results also demonstrate a dissociation between placebo-suggestion and non-hypnotic imaginative suggestion.

Placebo-Suggestion Modulates Conflict Resolution in the Stroop Task

PubMed Central

Caspar, Emilie A.; Gevers, Wim; Cleeremans, Axel

2013-01-01

Here, we ask whether placebo-suggestion (without any form of hypnotic induction) can modulate the resolution of cognitive conflict. Naïve participants performed a Stroop Task while wearing an EEG cap described as a “brain wave” machine. In Experiment 1, participants were made to believe that the EEG cap would either enhance or decrease their color perception and performance on the Stroop task. In Experiment 2, participants were explicitly asked to imagine that their color perception and performance would be enhanced or decreased (non-hypnotic imaginative suggestion). We observed effects of placebo-suggestion on Stroop interference on accuracy: interference was decreased with positive suggestion and increased with negative suggestion compared to baseline. Intra-individual variability was also increased under negative suggestion compared to baseline. Compliance with the instruction to imagine a modulation of performance, on the other hand, did not influence accuracy and only had a negative impact on response latencies and on intra-individual variability, especially in the congruent condition of the Stroop Task. Taken together, these results demonstrate that expectations induced by a placebo-suggestion can modulate our ability to resolve cognitive conflict, either facilitating or impairing response accuracy depending on the suggestion’s contents. Our results also demonstrate a dissociation between placebo-suggestion and non-hypnotic imaginative suggestion. PMID:24130735

New approaches in the management of insomnia: weighing the advantages of prolonged-release melatonin and synthetic melatoninergic agonists

PubMed Central

Hardeland, Rüdiger

2009-01-01

Hypnotic effects of melatonin and melatoninergic drugs are mediated via MT1 and MT2 receptors, especially those in the circadian pacemaker, the suprachiasmatic nucleus, which acts on the hypothalamic sleep switch. Therefore, they differ fundamentally from GABAergic hypnotics. Melatoninergic agonists primarily favor sleep initiation and reset the circadian clock to phases allowing persistent sleep, as required in circadian rhythm sleep disorders. A major obstacle for the use of melatonin to support sleep maintenance in primary insomnia results from its short half-life in the circulation. Solutions to this problem have been sought by developing prolonged-release formulations of the natural hormone, or melatoninergic drugs of longer half-life, such as ramelteon, tasimelteon and agomelatine. With all these drugs, improvements of sleep are statistically demonstrable, but remain limited, especially in primary chronic insomnia, so that GABAergic drugs may be indicated. Melatoninergic agonists do not cause next-day hangover and withdrawal effects, or dependence. They do not induce behavioral changes, as sometimes observed with z-drugs. Despite otherwise good tolerability, the use of melatoninergic drugs in children, adolescents, and during pregnancy has been a matter of concern, and should be avoided in autoimmune diseases and Parkinsonism. Problems and limits of melatoninergic hypnotics are compared. PMID:19557144

Use of psychotropic drugs before pregnancy and the risk for induced abortion: population-based register-data from Finland 1996-2006

PubMed Central

2010-01-01

Background Some, though not all studies have reported an increased risk for mental health problems after an induced abortion. Problems with design and data have compromised these studies and the generalisation of their results. Methods The Finnish Medication and Pregnancy database (N = 622 671 births and 114 518 induced abortions for other than fetal reasons) in 1996-2006 was utilised to study the use of psychotropic drugs in the three months before a pregnancy ending in a birth or an induced abortion. Results In total 2.1% of women with a birth and 5.1% of women with an induced abortion had used a psychotropic medicine 0-3 months before pregnancy. Psychotropic drug users terminated their pregnancies (30.9%) more often than other pregnant women (15.5%). Adjustment for background characteristics explained one third of this elevated risk, but the risk remained significantly increased among users of psychotropic medicine (OR 1.94, 95% confidence intervals 1.87-2.02). A similar risk was found for first pregnancies (30.1% vs. 18.9%; adjusted OR 1.53, 95% confidence intervals 1.42-1.65). The rate for terminating pregnancy was the highest for women using hypnotics and sedatives (35.6% for all pregnancies and 29.1% for first pregnancies), followed by antipsychotics (33.9% and 36.0%) and antidepressants (32.0% and 32.1%). Conclusions The observed increased risk for induced abortion among women with psychotropic medication highlighs the importance to acknowledge the mental health needs of women seeking an induced abortion. Further studies are needed to establish the impact of pre-existing differences in mental health on mental health outcomes of induced abortions compared to outcomes of pregnancies ending in a birth. PMID:20591182

The effect of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), pentobarbital and methaqualone on punished responding in control and 5,7-dihydroxytryptamine-treated rats.

PubMed

Commissaris, R L; Lyness, W H; Rech, R H

1981-05-01

The purpose of the present study was to determine the role of central 5-hydroxytryptamine (5-HT) neuronal systems in the effects of d-lysergic acid diethylamide (LSD), 2,5-methoxy-4-methylamphetamine (DOM), pentobarbital (PB) and methaqualone (MQ) on punished responding in rats. Water-deprived rats were trained to drink from a tube that was electrified at intervals (variable interval 21 sec; 0.03 mA current intensity), electrification being signalled by a tone. In daily 10-min control sessions, these animals accepted a relatively constant number of shocks; water consumption was also quite stable. At maximally effective doses PB, and to a lesser extent MQ, produced large (400-600 percent of control) increases in punished responding with little decrease in water intake. Higher doses of these agents produced a significant depression of unpunished responding (water intake). The hallucinogens, on the other hand, produced only moderate (125-175 percent of control) increases in the number of shock received, yet a similar depression of unpunished responding. Selective destruction of 5-HT neurons by intracerebroventricular administration of the neurotoxin 5,7-dihydroxytryptamine per se produced little change in the number of shocks received or water consumed in controls sessions. This destruction of 5-HT neurons failed to alter the effects of PB or MQ on punished or unpunished responding. The increase in punished responding produced by the hallucinogens, however, was blocked by this destruction of 5-HT neurons. Furthermore, the capacity of the hallucinogens to decrease water intake was significantly potentiated by the neurotoxin pretreatment. These data demonstrate that the effects of the hallucinogens LSD and DOM on conditioned suppression are quite different from those of PB and MQ, and that this difference may be due to the extent of 5-HT involvement in the effects of these agents.

Anxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways.

PubMed

Brito, Adriane F; Fajemiroye, James O; Neri, Hiasmin F S; Silva, Dayane M; Silva, Daiany P B; Sanz, Germán; Vaz, Boniek G; de Carvalho, Flávio S; Ghedini, Paulo C; Lião, Luciano M; Menegatti, Ricardo; Costa, Elson A

2017-09-01

In this study, we proposed the design, synthesis of a new compound 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032), and pharmacological evaluation of its anxiolytic-like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital-induced sleep, open-field and wire tests. The anxiolytic-like effect of this compound was evaluated using elevated plus maze and light-dark box tests. In addition, the mnemonic activity was evaluated through step-down test. In sodium pentobarbital-induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open-field test, LQFM032 altered behavioral parameter, that suggested anxiolytic-like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light-dark box test, the LQFM032 showed anxiolytic-like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1-(2-Methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic-like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic-like activity without altering the mnemonic activity. © 2017 John Wiley & Sons A/S.

Intravenous anaesthetics inhibit nicotinic acetylcholine receptor-mediated currents and Ca2+ transients in rat intracardiac ganglion neurons

PubMed Central

Weber, Martin; Motin, Leonid; Gaul, Simon; Beker, Friederike; Fink, Rainer H A; Adams, David J

2004-01-01

The effects of intravenous (i.v.) anaesthetics on nicotinic acetylcholine receptor (nAChR)-induced transients in intracellular free Ca2+ concentration ([Ca2+]i) and membrane currents were investigated in neonatal rat intracardiac neurons. In fura-2-loaded neurons, nAChR activation evoked a transient increase in [Ca2+]I, which was inhibited reversibly and selectively by clinically relevant concentrations of thiopental. The half-maximal concentration for thiopental inhibition of nAChR-induced [Ca2+]i transients was 28 μM, close to the estimated clinical EC50 (clinically relevant (half-maximal) effective concentration) of thiopental. In fura-2-loaded neurons, voltage clamped at −60 mV to eliminate any contribution of voltage-gated Ca2+ channels, thiopental (25 μM) simultaneously inhibited nAChR-induced increases in [Ca2+]i and peak current amplitudes. Thiopental inhibited nAChR-induced peak current amplitudes in dialysed whole-cell recordings by ∼ 40% at −120, −80 and −40 mV holding potential, indicating that the inhibition is voltage independent. The barbiturate, pentobarbital and the dissociative anaesthetic, ketamine, used at clinical EC50 were also shown to inhibit nAChR-induced increases in [Ca2+]i by ∼40%. Thiopental (25 μM) did not inhibit caffeine-, muscarine- or ATP-evoked increases in [Ca2+]i, indicating that inhibition of Ca2+ release from internal stores via either ryanodine receptor or inositol-1,4,5-trisphosphate receptor channels is unlikely. Depolarization-activated Ca2+ channel currents were unaffected in the presence of thiopental (25 μM), pentobarbital (50 μM) and ketamine (10 μM). In conclusion, i.v. anaesthetics inhibit nAChR-induced currents and [Ca2+]i transients in intracardiac neurons by binding to nAChRs and thereby may contribute to changes in heart rate and cardiac output under clinical conditions. PMID:15644873

Antagonism of the Ethanol-Like Discriminative Stimulus Effects of Ethanol, Pentobarbital, and Midazolam in Cynomolgus Monkeys Reveals Involvement of Specific GABAA Receptor SubtypesS⃞

PubMed Central

Rogers, Laura S. M.; Grant, Kathleen A.

2009-01-01

The γ-aminobutyric acid (GABA)A receptors mediating the discriminative stimulus effects of ethanol were studied by comparing the potency of ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)benzodiazepine-3-carboxylate (Ro15-4513) and ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazol(1,5-a)-benzodiazepine-3-carboxylate (flumazenil, Ro15-1788) to antagonize ethanol, pentobarbital (PB), and midazolam substitution for ethanol. Ro15-4513 has high affinity for receptors containing α4/6 and α5 subunits and lower affinity for α1, α2, and α3 subunits. Flumazenil is nonselective for GABAA receptors containing α1, α2, α3, and α5 subunits and has low affinity for α4/6-containing receptors. Male (n = 9) and female (n = 8) cynomolgus monkeys (Macaca fascicularis) were trained to discriminate ethanol (1.0 or 2.0 g/kg i.g., 30-min pretreatment) from water. Ethanol, PB, and midazolam dose-dependently substituted for ethanol (80% ethanol-appropriate responding). Ro15-4513 (0.003–0.56 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in a vast majority of monkeys tested (15/15, 16/17, and 11/12, respectively). In contrast, flumazenil (0.30–10.0 mg/kg i.m., 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in 9 of 16, 12 of 16, and 7 of 9 monkeys tested, respectively. In the monkeys showing antagonism with both Ro15-4513 and flumazenil, ethanol and PB substitution were antagonized more potently by Ro15-4513 than by flumazenil, whereas midazolam substitution was antagonized with similar potency. There were no sex or training dose differences, with the exception that flumazenil failed to antagonize ethanol substitution in males trained to discriminate 2.0 g/kg ethanol. GABAA receptors with high affinity for Ro15-4513 (i.e., containing α4/6 and α5 subunits) may be particularly important mediators of the multiple discriminative stimulus effects of ethanol

Influence of dosage, consciousness, and nifedipine on the acute pressor response to intraperitoneally administered cadmium. [Rats

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

Hall, C.E.; Hungerford, S.

1982-05-01

The acute pressor effect of intraperitoneally administered cadmium was explored over the dose range 0.015-2 mg/kg in both pentobarbital-anesthetized and conscious rats. The former first respondent at 0.031 mg/kg, and successive doublings of that dosage increased the highest pressures attained in a stepwise fashion until a dosage of 0.25 mg/kg, the maximally effective quantity, was reached. Arterial pressure did not rise in conscious rats until a dose of 1 mg/kg, which gave the maximum response within the range examined. Heart-rate changes with Cd were slight, and rarely significant at a given dosage, but pentobarbital invariably caused tachycardia. Anesthetized rats thusmore » gave a graded response, while conscious animals reacted in an all-or-none fashion. The increased pressor responsiveness of rats under pentobarbital can not be ascribed to its cardiac parasympatholytic effects, since sensitivity was not conferred upon conscious rats when pretreated with atropine at a dose producing even greater tachycardia than that caused by pentobarbital. Nifedipine, which blocks calcium entry into smooth muscle cells, prevented the pressor response to cadmium when given as pretreatment and terminated an ongoing response when give intercurrently. Possible mechanisms to account for the observed behavior are considered.« less

Mediators of a brief hypnosis intervention to control side effects in breast surgery patients: Response expectancies and emotional distress

PubMed Central

Montgomery, Guy H.; Hallquist, Michael N.; Schnur, Julie B.; David, Daniel; Silverstein, Jeffrey H.; Bovbjerg, Dana H.

2010-01-01

Hypnosis is widely recognized as an empirically supported intervention to improve postsurgical outcomes. However, to date, no research has examined mediators of hypnotic benefit among surgery patients. The present study was designed to test the hypotheses that response expectancies and emotional distress would mediate the effects of an empirically validated presurgical hypnosis intervention on postsurgical side effects (i.e., pain, nausea, and fatigue). In a sample of 200 women undergoing breast conserving surgery (mean age = 48.50 years), structural equation modeling revealed the following: 1) hypnotic effects on postsurgical pain were partially mediated by pain expectancy (p< .0001), but not by distress (p=.12); 2) hypnotic effects on postsurgical nausea were partially mediated by presurgical distress (p=.02), but not by nausea expectancy (p=.10); 3) hypnotic effects on postsurgical fatigue were partially mediated by both fatigue expectancy (p=.0001) and presurgical distress (p=.02). These results improve understanding of the underlying mechanisms responsible for hypnotic phenomena in the surgical setting, and suggest that future hypnotic interventions target patient expectancies and distress to improve postsurgical recovery. PMID:20099953

Cardiovascular effects of torcetrapib in conscious and pentobarbital-anesthetized dogs.

PubMed

Polakowski, James S; King, Andrew J; Campbell, Thomas J; Nelson, Richard A; Preusser, Lee C; Kempf-Grote, Anita J; Marsh, Kennan C; Gintant, Gary A; Cox, Bryan F; Mittelstadt, Scott W

2009-12-01

Torcetrapib is a cholesteryl ester transfer protein inhibitor with an undesired response of increasing arterial pressure in humans. Pressor responses to torcetrapib have been demonstrated in multiple preclinical species. However, these studies have not related plasma concentrations to observed effects. Our purpose was to 1) characterize the cardiovascular responses of torcetrapib in conscious and anesthetized dogs with measured plasma concentrations; and 2) characterize the hemodynamic effects contributing to hypertension using comprehensively instrumented anesthetized dogs. Torcetrapib was dosed orally (3, 30 mg/kg) and intravenously (0.01, 0.33, 0.1 mg/kg) in conscious and anesthetized dogs, respectively. Mean arterial pressure and heart rate were monitored in both models; additional parameters were measured in anesthetized dogs. Plasma drug concentrations were assessed in both models. In conscious and anesthetized dogs, torcetrapib increased mean arterial pressure 25 and 18 mm Hg and heart rate 35 and 21 beats/min, at 2.94 and 3.99 microg/mL, respectively. In anesthetized dogs, torcetrapib increased pulmonary arterial pressure, both systemic and pulmonary hypertension driven by increases in vascular resistance. The compound increased rate pressure product and myocardial contractility while decreasing time to systolic pressure recovery and ejection time. Thus, torcetrapib-induced pressor responses are mediated by systemic and pulmonary vasoconstriction and are associated with increased myocardial oxygen consumption and positive inotropy.

Effects of general anesthetics on substance P release and c-Fos expression in the spinal dorsal horn

PubMed Central

Takasusuki, Toshifumi; Yamaguchi, Shigeki; Hamaguchi, Shinsuke; Yaksh, Tony L.

2013-01-01

Background We examined in vivo the effects of general anesthetics on evoked substance P release (primary afferent excitability) and c-Fos expression (neuronal activation) in superficial dorsal horn. Methods Rats received saline, propofol (100mg/kg), pentobarbital (50mg/kg), isoflurane (2 minimum alveolar concentration), nitrous oxide (66%) or fentanyl (30μg/kg). During anesthesia, rats received intraplantar 5% formalin (50μl) to left hindpaw. Ten min later, rats underwent transcardial perfusion with 4% paraformaldehyde. Substance P release from small primary afferents was assessed by incidence of Neurokinin 1 receptor (NK1r) internalization in the superficial dorsal horn. In separate studies, rats were sacrificed after 2 hrs and c-Fos expression measured. Results Intraplantar formalin induced robust NK1r internalization in ipsilateral dorsal horn (ipsilateral: 54±6% [mean±SEM], contralateral: 12±2%, P<0.05, n=4). Fentanyl, but not propofol, pentobarbital, isoflurane nor nitrous oxide alone inhibited NK1r internalization. However, 2 minimum alveolar concentration isoflurane + nitrous oxide reduced NK1r internalization (27±3%, P<0.05, n=5). All agents reduced c-Fos expression (control: 34±4, fentanyl: 8±2, isoflurane: 12±3, nitrous oxide: 11±2, isoflurane + nitrous oxide: 12±1, pentobarbital: 11±2, propofol: 13±3, P<0.05, n=3). Conclusion General anesthetics at anesthetic concentrations block spinal neuron activation through a mechanism which is independent of an effect upon small primary afferent peptide release. The effect of fentanyl alone and the synergistic effect of isoflurane and nitrous oxide on substance P release suggests a correlative rationale for the therapeutic use of these anesthetic protocol by blocking nociceptive afferent transmitter release and preventing the initiation of cascade which are immediately postsynaptic to the primary afferent. PMID:23708866

Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2010-09-30

a novel hypocretiniorexin antagonist, almorexant (ALM), to a standard hypnotic , zolpidem (ZOL), and placebo (PBO) on neurocognitive performance at...Placebo-Controlled, Randomized, Parallel- Group Study Comparing the Effect of a Novel HypocretiniOrexin Antagonist (Almorexant) Versus a Standard Hypnotic ...Group Study Comparing the Effect of a Novel HypocretiniOrexin Antagonist (Almorexant) Versus a Standard Hypnotic (Zolpidem) and Placebo on

Plasticity-Related Gene Expression During Eszopiclone-Induced Sleep.

PubMed

Gerashchenko, Dmitry; Pasumarthi, Ravi K; Kilduff, Thomas S

2017-07-01

Experimental evidence suggests that restorative processes depend on synaptic plasticity changes in the brain during sleep. We used the expression of plasticity-related genes to assess synaptic plasticity changes during drug-induced sleep. We first characterized sleep induced by eszopiclone in mice during baseline conditions and during the recovery from sleep deprivation. We then compared the expression of 18 genes and two miRNAs critically involved in synaptic plasticity in these mice. Gene expression was assessed in the cerebral cortex and hippocampus by the TaqMan reverse transcription polymerase chain reaction and correlated with sleep parameters. Eszopiclone reduced the latency to nonrapid eye movement (NREM) sleep and increased NREM sleep amounts. Eszopiclone had no effect on slow wave activity (SWA) during baseline conditions but reduced the SWA increase during recovery sleep (RS) after sleep deprivation. Gene expression analyses revealed three distinct patterns: (1) four genes had higher expression either in the cortex or hippocampus in the group of mice with increased amounts of wakefulness; (2) a large proportion of plasticity-related genes (7 out of 18 genes) had higher expression during RS in the cortex but not in the hippocampus; and (3) six genes and the two miRNAs showed no significant changes across conditions. Even at a relatively high dose (20 mg/kg), eszopiclone did not reduce the expression of plasticity-related genes during RS period in the cortex. These results indicate that gene expression associated with synaptic plasticity occurs in the cortex in the presence of a hypnotic medication. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Hypnosis and pain perception: An Activation Likelihood Estimation (ALE) meta-analysis of functional neuroimaging studies.

PubMed

Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; De Rossi, Pietro; Angeletti, Gloria; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2015-12-01

Several studies reported that hypnosis can modulate pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. We conducted an Activation Likelihood Estimation (ALE) meta-analysis on functional neuroimaging studies of pain perception under hypnosis to identify brain activation-deactivation patterns occurring during hypnotic suggestions aiming at pain reduction, including hypnotic analgesic, pleasant, or depersonalization suggestions (HASs). We searched the PubMed, Embase and PsycInfo databases; we included papers published in peer-reviewed journals dealing with functional neuroimaging and hypnosis-modulated pain perception. The ALE meta-analysis encompassed data from 75 healthy volunteers reported in 8 functional neuroimaging studies. HASs during experimentally-induced pain compared to control conditions correlated with significant activations of the right anterior cingulate cortex (Brodmann's Area [BA] 32), left superior frontal gyrus (BA 6), and right insula, and deactivation of right midline nuclei of the thalamus. HASs during experimental pain impact both cortical and subcortical brain activity. The anterior cingulate, left superior frontal, and right insular cortices activation increases could induce a thalamic deactivation (top-down inhibition), which may correlate with reductions in pain intensity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sleep, performance, and plasma levels in chronic insomniacs during 14-day use of flurazepam and midazolam: an introduction.

PubMed

Johnson, L C; Chernik, D A; Sateia, M J

1990-08-01

A review of the published literature reveals many unanswered questions regarding the effects of sedative-hypnotics on sleep, performance, and mood. The relationship between plasma half-life and hypnotic efficacy is also not clear. A randomized, double-blind, parallel-groups, multicenter study was designed to examine sleep, performance, and mood in patients with insomnia. A large, heterogeneous sample of patients with a history of benzodiazepine use for chronic insomnia was chosen to reflect the adult population for which sedative-hypnotics are often prescribed and to ensure statistical reliability. Although the major focus of the current study was on the effects of two benzodiazepine hypnotics on performance, this study also provided information on the following important issues: (1) effect of dose level; (2) short-versus long-term administration; and (3) significance of plasma half-life as it relates to hypnotic efficacy.

Episodic and semantic memory in posthypnotic amnesia: A reevaluation.

PubMed

Spanos, N P; Radtke, H L; Dubreuil, D L

1982-09-01

Recently, Kihlstrom found that a suggestion for posthypnotic amnesia produced impairments on episodic but not semantic memory tasks. During amnesia testing, highly and very highly susceptible subjects showed reduced recall for a previously learned word list but no deficits on a word association task designed to elicit the forgotten words as associates. He hypnotized that posthypnotic amnesia involved a dissociation between episodic and semantic components of memory. We tested the alternative hypothesis that Kihlstrom's findings resulted from experimental demands conveyed by the wording of the amnesia suggestion he employed. We found that subjects could be induced to show only episodic impairments (thereby replicating Kihlstrom) or both episodic and semantic impairments (contrary to Kihlstrom) by subtly varying the wording of amnesia suggestions. These findings are inconsistent with a dissociation hypothesis. Instead, they support the notion that hypnotic amnesia is a strategic enactment strongly influenced by expectations generated in the amnesia testing situation.

Marine Aviation Weapons and Tactics Squadron One (MAWTS-1): Sleep, Fatigue, and Aviator Performance Study

DTIC Science & Technology

2008-12-01

hypnotics , referred to as “go and no-go” pills, respectively, that help aviators maintain alertness and performance or acquire restorative sleep...Stimulants used in the aviation community are amphetamines, caffeine, and modafinil. Hypnotics may include temazepam, zolpidem, and possibly melatonin...Both stimulants and hypnotics may be available through prescriptions or over-the-counter, but the flight surgeon must always approve any medication

Hypnosis and behavioral treatment in a worksite smoking cessation program.

PubMed

Frank, R G; Umlauf, R L; Wonderlich, S A; Ashkanazi, G S

1986-01-01

In the initial study, 48 subjects of the total (N = 63) ultimately used, were assigned to one of three treatments: four hypnotic sessions with a booster, two hypnotic sessions, or two hypnotic and two behavioral sessions with a booster. A follow-up group was later recruited composed of 15 subjects who received four hypnotic sessions and a booster session with less time between sessions. The results indicated no difference in smoking cessation 6 months after treatment regardless of the frequency, length between sessions, or addition of behavioral methods. Successful subjects were more educated, less able to utilize their imagination, and had fewer smokers at home.

Effect of a Hypocretin/Orexin Antagonist on Neurocognitive Performance

DTIC Science & Technology

2012-09-01

cells are more strongly activated by ZOL (Task 4a). Lesions of the basal forebrain (BF), a wakefulness-promoting area, potentiated the hypnotic ...receptor antagonist with a novel mechanism of action that has shown promise as an effective hypnotic . Preclinical data demonstrate that animals...results are consistent with the hypothesis that, although both ALM and ZOL are effective hypnotic medications, rats would show less functional impairment

[Behavioral pharmacological properties of nicergoline. Effects on gross-behavior in rats and monkeys and on DRL response, CER, and CAR in rats].

PubMed

Yamamura, M; Maeda, K; Nakagawa, H; Ishida, R

1986-02-01

Whether nicergoline has psychotropic-like pharmacological properties was examined through the gross-behavioral and operant behavioral observations in rats and monkeys. In gross-behavioral observations, slight decrement of spontaneous motor activity, lying on the abdomen and relaxation of abdominal tone were observed in rats when nicergoline was administered intravenously (1 mg/kg or more) and intraperitoneally (4 mg/kg or more). However, when it was administered orally, slight decrement of spontaneous motor activity was observed only at large doses of 32 and 128 mg/kg. In monkeys, nicergoline produced decrement of spontaneous motor activity, palpebral ptosis, and lacrimation when administered intraperitoneally at doses of 1 mg/kg or more. Under a differential reinforcement of low rate (DRL) schedule for food reinforcement in rats, nicergoline depressed the response at 4 mg/kg, i.p., or 128 mg/kg, orally. In conditioned emotional response (CER), nicergoline had no effect on the responses during both the alarm and safe periods at doses of 0.25, 1, and 4 mg/kg, i.p., or 8, 32, and 128 mg/kg, p.o. In Sidman continuous avoidance response (CAR), nicergoline (0.25, 1, and 4 mg/kg, i.p., or 8, 32, and 128 mg/kg, p.o.) slightly depressed the response and increased the total shock. These results were compared with those of chlorpromazine, chlordiazepoxide, pentobarbital, and methamphetamine and the following conclusion was drawn: Inhibitory effects of nicergoline on gross and operant behaviors seem to be non-specific, and its behavioral pharmacological properties are qualitatively different from those of anti-psychotics, anti-anxietics, hypnotics, and stimulants.

21 CFR 522.1704 - Pentobarbital.

Code of Federal Regulations, 2014 CFR

2014-04-01

... and hypnosis and may be supplemented with a local anesthetic. It may also be used in dogs for the.... The drug is administered intravenously “to effect”. For general surgical anesthesia, the usual dose is... for use. The drug is indicated for use as a general anesthetic in dogs and cats. Although it may be...

Physiologic, Behavioral, and Histologic Responses to Various Euthanasia Methods in C57BL/6NTac Male Mice.

PubMed

Boivin, Gregory P; Bottomley, Michael A; Schiml, Patricia A; Goss, Lori; Grobe, Nadja

2017-01-01

Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as more humane methods of euthanasia. In this study, we examined 3 commonly used euthanasia methods in mice: intraperitoneal injection of pentobarbital-phenytoin solution, CO2 inhalation, and isoflurane anesthesia followed by CO2 inhalation. We hypothesized that pentobarbital-phenytoin euthanasia would cause fewer alterations in cardiovascular response, result in less behavioral evidence of pain or stress, and produce lower elevations in ACTH than would the isoflurane and CO2 methods, which we hypothesized would not differ in regard to these parameters. ACTH data suggested that pentobarbital-phenytoin euthanasia may be less stressful to mice than are isoflurane and CO2 euthanasia. Cardiovascular, behavioral, and activity data did not consistently or significantly support isoflurane or pentobarbital-phenytoin euthanasia as less stressful methods than CO2. Euthanasia with CO2 was the fastest method of the 3 techniques. Therefore, we conclude that using CO2 with or without isoflurane is an acceptable euthanasia method. Pathologic alterations in the lungs were most severe with CO2 euthanasia, and alternative euthanasia techniques likely are better suited for studies that rely on analysis of the lungs.

Evaluation of a Commercially Available Euthanasia Solution as a Voluntarily Ingested Euthanasia Agent in Laboratory Mice.

PubMed

Dudley, Emily S; Boivin, Gregory P

2018-01-01

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice of various strains. We first explored the palatability of sugar-cookie dough with various flavorings added. We placed the cookie dough in the cage with an adult mouse and recorded the amount ingested after 1 h. Mice readily ingested all flavors of sugar-cookie dough. We then added a euthanasia solution containing pentobarbital and phenytoin to all flavors of cookie dough and placed a small bolus in the cage of each mouse or mouse pair. We observed the mice for 1 h for clinical signs of pentobarbital intoxication and then weighed uneaten dough to determine the dose of pentobarbital ingested. Palatability declined sharply when euthanasia solution was present. Mice ingested higher doses of pentobarbital in cookie dough during the dark phase and after fasting. Ingestion caused ataxia in some mice but was not sufficient to cause loss of righting reflex, unconsciousness, or death in any mouse. We successfully identified sugar cookie dough as a drug vehicle that was readily and rapidly eaten by mice without the need for previous exposure. Additional research is needed to identify euthanasia compounds for mice that do not affect the palatability of cookie dough.

Evaluation of a Commercially Available Euthanasia Solution as a Voluntarily Ingested Euthanasia Agent in Laboratory Mice

PubMed Central

Dudley, Emily S; Boivin, Gregory P

2018-01-01

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice of various strains. We first explored the palatability of sugar-cookie dough with various flavorings added. We placed the cookie dough in the cage with an adult mouse and recorded the amount ingested after 1 h. Mice readily ingested all flavors of sugar-cookie dough. We then added a euthanasia solution containing pentobarbital and phenytoin to all flavors of cookie dough and placed a small bolus in the cage of each mouse or mouse pair. We observed the mice for 1 h for clinical signs of pentobarbital intoxication and then weighed uneaten dough to determine the dose of pentobarbital ingested. Palatability declined sharply when euthanasia solution was present. Mice ingested higher doses of pentobarbital in cookie dough during the dark phase and after fasting. Ingestion caused ataxia in some mice but was not sufficient to cause loss of righting reflex, unconsciousness, or death in any mouse. We successfully identified sugar cookie dough as a drug vehicle that was readily and rapidly eaten by mice without the need for previous exposure. Additional research is needed to identify euthanasia compounds for mice that do not affect the palatability of cookie dough. PMID:29402349

The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers.

PubMed

Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

2017-08-01

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO 2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO 2 inhalation and decapitation. CO 2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers

PubMed Central

Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

2018-01-01

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO2 inhalation and decapitation. CO2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. PMID:28244216

Effects of relaxation on the delayed-type hypersensitivity (DTH) reaction to diphenylcyclopropenone (DCP).

PubMed

Zachariae, R; Jørgensen, M M; Christensen, S; Bjerring, P

1997-07-01

Delayed-type hypersensitivity (DTH) reactions to the experimental allergen diphenylcyclopropenone (DCP) were measured in four groups, which either trained (+) or did not train in relaxation (-) during the sensitization and/or the challenge phase. All groups consisted of high and low hypnotic susceptible subjects. While there were no differences in erythema, the mean induration of the group which trained in relaxation in both the sensitization and the challenge phase (+/+) was significantly greater than that of the group which trained in relaxation in the challenge phase only (-/+). Significant correlations were found between induration and hypnotic susceptibility scores, and between induration and degree of perceived relaxation during challenge. High hypnotic susceptible subjects experienced a higher degree of perceived relaxation and exhibited greater indurative and erythematous DTH reactions to DCP than low hypnotic susceptible subjects in all four experimental conditions. Though the mediating mechanisms remain unclear, our results suggest that relaxation may affect the DTH reaction, and support previous findings of higher psychophysiologic reactivity of high hypnotic susceptible subjects.

Effect of p-amino-diphenyl ethers on hepatic microsomal cytochrome P450.

PubMed

Jiang, Huidi; Xuan, Guida

2003-09-01

The present paper aims to investigate whether p-amino-2',4'-dichlorodiphenyl ether and p-amino-4'-methyldiphenyl ether are inhibitors as well as inducers of P450. Mice were given daily intraperitoneal (ip) injections of p-amino-2',4'-dichlorodiphenyl ether (0.25 mmol/kg) or p-amino-4'-methyldiphenyl ether (0.25 mmol/kg) for 4 days and tested at 24 h and 48 h after the last dose injection. The results showed the mice pentobarbital sleeping time was shorter and the P450 content of hepatic microsome increased significantly in the group pretreated with p-amino-4'-methyldiphenyl ether when compared with the control group, while in mice pretreated with p-amino-2',4'-dichlorodiphenyl ether the hepatic microsome P450 content increased but the pentobarbital sleeping time was extended in clear contrast to the control group. The sleeping time of the phenobarbital group (80 mg/kg daily ip injection for 4 days) was shortened at 24 h after the last injection with increased P450 content of hepatic microsome, but it showed no difference at 48 h. The zoxazolamine-paralysis times of mice treated with p-amino-2',4'-dichlorodiphenyl ether were longer than those of the control mice, while the same dose of zoxazolamine did not lead to paralysis in mice pretreated with BNF. p-Amino-2',4'-dichlorodiphenyl ether and p-amino-4'-methyldiphenyl ether inhibited the activity of 7-ethoxyresorufin O-deethylase from rat hepatic microsome induced by BNF in vitro by 70.0% and 50.1% respectively. These results suggest that p-amino-2',4'-dichlorodiphenyl ether and p-amino-4'-methyldiphenyl ether are inhibitors as well as inducers of P450.

Functional brain imaging and the induction of traumatic recall: a cross-correlational review between neuroimaging and hypnosis.

PubMed

Vermetten, Eric; Douglas Bremner, J

2004-07-01

The behavioral and psychophysiological alterations during recall in patients with trauma disorders often resemble phenomena that are seen in hypnosis. In studies of emotional recall as well as in neuroimaging studies of hypnotic processes similar brain structures are involved: thalamus, hippocampus, amygdala, medial prefrontal cortex, anterior cingulate cortex. This paper focuses on cross-correlations in traumatic recall and hypnotic responses and reviews correlations between the involvement of brain structures in traumatic recall and processes that are involved in hypnotic responsiveness. To further improve uniformity of results of brain imaging specifically for traumatic recall studies, attention is needed for standardization of hypnotic variables, isolation of the emotional process of interest (state),and assessment of trait-related differences.

New directions in hypnosis research: strategies for advancing the cognitive and clinical neuroscience of hypnosis

PubMed Central

Jensen, Mark P; Jamieson, Graham A; Lutz, Antoine; Mazzoni, Giuliana; McGeown, William J; Santarcangelo, Enrica L; Demertzi, Athena; De Pascalis, Vilfredo; Bányai, Éva I; Rominger, Christian; Vuilleumier, Patrik; Faymonville, Marie-Elisabeth; Terhune, Devin B

2017-01-01

Abstract This article summarizes key advances in hypnosis research during the past two decades, including (i) clinical research supporting the efficacy of hypnosis for managing a number of clinical symptoms and conditions, (ii) research supporting the role of various divisions in the anterior cingulate and prefrontal cortices in hypnotic responding, and (iii) an emerging finding that high hypnotic suggestibility is associated with atypical brain connectivity profiles. Key recommendations for a research agenda for the next decade include the recommendations that (i) laboratory hypnosis researchers should strongly consider how they assess hypnotic suggestibility in their studies, (ii) inclusion of study participants who score in the middle range of hypnotic suggestibility, and (iii) use of expanding research designs that more clearly delineate the roles of inductions and specific suggestions. Finally, we make two specific suggestions for helping to move the field forward including (i) the use of data sharing and (ii) redirecting resources away from contrasting state and nonstate positions toward studying (a) the efficacy of hypnotic treatments for clinical conditions influenced by central nervous system processes and (b) the neurophysiological underpinnings of hypnotic phenomena. As we learn more about the neurophysiological mechanisms underlying hypnosis and suggestion, we will strengthen our knowledge of both basic brain functions and a host of different psychological functions. PMID:29034102

Reply to Wagstaff: "Hypnosis and the relationship between trance, suggestion, expectancy, and depth: some semantic and conceptual issues".

PubMed

Pekala, Ronald J

2011-01-01

Wagstaff (2010) reviews and comments on two recent papers by Pekala et al. (2010a, 2010b), concluding that "many of the problems relating to the definition and conceptualization of terms associated with hypnosis... may stem from insufficient attention to the role of suggestion and expectancies in producing hypnotic phenomena, and an over-reliance on the role of the procedures and mechanics of the induction process" (p. 47). Although I agree with his semantic and conceptual focus, I believe that a number of these problems are due to not operationally defining terms such as hypnosis, hypnotic state, or trance in a comprehensive phenomenological manner. By using the PCI (Phenomenology of Consciousness Inventory) via retrospective phenomenological assessment, and using a phenomenological state instrument like the PCI-HAP (Phenomenology of Consciousness Inventory - Hypnotic Assessment Procedure) to obtain a state measure of hypnotic responsiveness, a means is available to define and empirically address some of these issues in a way that can significantly further our understanding of the nature of hypnotism. Such an approach might also address Kallio and Revonsuo's (2005) admonition concerning the need to develop "an internally coherent and widely shared theoretical vocabulary" (p. 51) to better understand consciousness, altered states of consciousness, and related phenomena, such as hypnosis/hypnotism.

VIRTUAL REALITY HYPNOSIS FOR PAIN CONTROL IN A PATIENT WITH GLUTEAL HIDRADENITIS:A CASE REPORT1

PubMed Central

SOLTANI, MARYAM; TEELEY, AUBRIANA M.; WIECHMAN, SHELLEY A.; JENSEN, MARK P.; SHARAR, SAM R.; PATTERSON, DAVID R.

2012-01-01

This case report describes the use of hypnotic analgesia induced through immersive three-dimensional computer-generated virtual reality, better known as virtual reality hypnosis (VRH), in the treatment of a patient with ongoing pain associated with gluteal hidradenitis, The patient participated in the study for two consecutive days white hospitalized at a regional trauma centre. At pretreatment, she reported severe pain intensity and unpleasantness as well as high levels of anxiety and nervousness. She was then administered two sessions of virtual reality hypnotic treatment for decreased pain and anxiety. The patient’s ratings of ‘time spent thinking about pain’, pain intensity, ‘unpleasantness of pain’, and anxiety decreased from before to after each daily VRH session, as well as from Day One to Day Two. The findings indicate that VRH may benefit individuals with severe, ongoing pain from a chronic condition, and that a controlled clinical trial examining its efficacy is warranted. PMID:23205274

The role of hypnosis in the detection of psychogenic seizures.

PubMed

Martínez-Taboas, Alfonso

2002-07-01

In this preliminary clinical investigation, hypnosis was used in the differential diagnosis of epileptic versus psychogenic seizures (PS). Eight patients with a clinical profile suggesting the presence of PS were given a hypnotic suggestion in which they had to go back in time to the exact moment of their last seizure. They were then asked to concentrate their attention on any unusual feeling or bodily sensation. All 8 patients presented a PS during the age regression protocol. In 6 cases, independent testimony from family members corroborated the morphological similarity of the induced attack and the ones presented in their natural environment. Also, the seizures ended abruptly after a command was given to stop them. A control group of 5 epileptic subjects did not present any signs of discomfort or seizure behavior during the hypnotic protocol. It is argued that a simple procedure as the one described in this investigation can be useful as a diagnostic tool in the differentiation of epileptic from PS attacks.

Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.

PubMed Central

Levitan, R D; Shen, J H; Jindal, R; Driver, H S; Kennedy, S H; Shapiro, C M

2000-01-01

OBJECTIVE: Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN: Randomized, double-blind, placebo-controlled trial. PATIENTS: Thirty individuals with major depressive disorder. INTERVENTIONS: Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES: Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS: During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS: Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings. PMID:11022398

Slowing of the hippocampal θ-rhythm correlates with anesthetic-induced amnesia

PubMed Central

Perouansky, Misha; Rau, Vinuta; Ford, Tim; Oh, S. Irene; Perkins, Mark; Eger, Edmond I.; Pearce, Robert A.

2010-01-01

Background Temporary, antegrade amnesia is one of the core desirable endpoints of general anesthesia. Multiple lines of evidence support a role for the hippocampal θ-rhythm, a synchronized rhythmic oscillation of field potentials at 4–12 Hz, in memory formation. Previous studies have revealed a disruption of the θ-rhythm at surgical levels of anesthesia. We hypothesized that modulation of θ-rhythm would also occur at subhypnotic but amnestic concentrations. Therefore we examined the effect of three inhaled agents on properties of the θ-rhythm that are considered to be critical for the formation of hippocampus-dependent memories. Methods We studied the effects of halothane and nitrous oxide, two agents known to modulate different molecular targets (GABAergic vs. non-GABAergic, respectively), and isoflurane (both GABAergic and non-GABAergic targets), on fear-conditioned learning and θ-oscillations in freely behaving rats. Results All three anesthetics slowed θ-peak frequency in proportion to their inhibition of fear conditioning (by 1 Hz, 0.7 Hz and 0.5 Hz for 0.32% isoflurane, 60% N2O and 0.24% halothane). The anesthetics inconsistently affected other characteristics of θ-oscillations. Conclusions At sub-hypnotic amnestic concentrations, θ-oscillation frequency was the parameter most consistently affected by these three anesthetics. These results are consistent with the hypothesis that modulation of the θ-rhythm contributes to anesthetic-induced amnesia. PMID:21042201

Ginkgo Biloba Ameliorates Subfertility Induced by Testicular Ischemia/Reperfusion Injury in Adult Wistar Rats: A Possible New Mitochondrial Mechanism

PubMed Central

Ahmed, Asmaa Ibrahim; El-Zawahry, Khaled Mohamed

2016-01-01

Testicular torsion, a surgical emergency, could affect the endocrine and exocrine testicular functions. This study demonstrates histopathological and physiological effects of testicular ischemia/perfusion (I/R) injury and the possible protective effects of Ginkgo biloba treatment. Fifty adult male Wistar rats, 180–200 gm, were randomly divided into sham-operated, Gingko biloba supplemented, ischemia only, I/R, and Gingko biloba treated I/R groups. Overnight fasted rats were anaesthetized by Pentobarbital; I/R was performed by left testis 720° rotation in I/R and treated I/R groups. Orchiectomy was performed for histopathological studies and detection of mitochondrial NAD+. Determination of free testosterone, FSH, TNF-α, and IL1-β in plasma was performed. Plasma-free testosterone was significantly decreased, while plasma FSH, TNF-α, IL-1β, and testicular mitochondrial NAD+ were significantly increased in I/R group compared to control group. These parameters were reversed in Gingko biloba treated I/R group compared to I/R group. I/R caused marked testicular damage and increased APAF-1 in the apoptotic cells which were reversed by Ginkgo biloba treatment. It could be concluded that I/R caused subfertility induced by apoptosis and oxidative stress manifested by the elevated testicular mitochondrial NAD+, which is considered a new possible mechanism. Also, testicular injury could be reduced by Gingko biloba administration alone. PMID:28101298

Ginkgo Biloba Ameliorates Subfertility Induced by Testicular Ischemia/Reperfusion Injury in Adult Wistar Rats: A Possible New Mitochondrial Mechanism.

PubMed

Ahmed, Asmaa Ibrahim; Lasheen, Noha N; El-Zawahry, Khaled Mohamed

2016-01-01

Testicular torsion, a surgical emergency, could affect the endocrine and exocrine testicular functions. This study demonstrates histopathological and physiological effects of testicular ischemia/perfusion (I/R) injury and the possible protective effects of Ginkgo biloba treatment. Fifty adult male Wistar rats, 180-200 gm, were randomly divided into sham-operated, Gingko biloba supplemented, ischemia only, I/R, and Gingko biloba treated I/R groups. Overnight fasted rats were anaesthetized by Pentobarbital; I/R was performed by left testis 720° rotation in I/R and treated I/R groups. Orchiectomy was performed for histopathological studies and detection of mitochondrial NAD + . Determination of free testosterone, FSH, TNF- α , and IL1- β in plasma was performed. Plasma-free testosterone was significantly decreased, while plasma FSH, TNF- α , IL-1 β , and testicular mitochondrial NAD + were significantly increased in I/R group compared to control group. These parameters were reversed in Gingko biloba treated I/R group compared to I/R group. I/R caused marked testicular damage and increased APAF-1 in the apoptotic cells which were reversed by Ginkgo biloba treatment. It could be concluded that I/R caused subfertility induced by apoptosis and oxidative stress manifested by the elevated testicular mitochondrial NAD + , which is considered a new possible mechanism. Also, testicular injury could be reduced by Gingko biloba administration alone.

Mechanism involved in Danshen-induced fluid secretion in salivary glands

PubMed Central

Wei, Fei; Wei, Mu-Xin; Murakami, Masataka

2015-01-01

AIM: Danshen’s capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia. METHODS: Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium. The artery was cannulated and vascularly perfused at a constant rate. The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance. The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated. In addition, the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption. In order to assess the mechanism involved in Danshen-induced fluid secretion, either ouabain (an inhibitor of Na+/K+ ATPase) or bumetanide (an inhibitor of NKCC1) was additionally applied during the Danshen stimulation. In order to examine the involvement of the main membrane receptors, atropine was added to block the M3 muscarinic receptors, or phentolamine was added to block the α1 adrenergic receptors. In order to examine the requirement for extracellular Ca2+, Danshen was applied during the perfusion with nominal Ca2+ free solution. RESULTS: Although Danshen induced salivary fluid secretion, 88.7 ± 12.8 μL/g-min, n = 9, (the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine, P = 0.00093 by t-test) in the submandibular glands, the time course of that secretion differed from that induced by carbamylcholine. There was a latency associated with the fluid secretion induced by Danshen, followed by a gradual increase in the secretion to its highest value, which was in turn followed by a slow decline to a near zero level. The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%, and suppressed the oxygen consumption by 49% or 66%, respectively. These results indicated that Danshen activates Na+/K+ ATPase

Pathophysiological Alterations In The Basolateral Amygdala And Neurodegeneration Of Limbic Structures During Epileptogenesis Induced By Status Epilepticus

DTIC Science & Technology

2009-02-05

Crestani F, Martin JR, Möhler H, and Rudolph U (2000) Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol 131:1251–56...epilepsy laterality and reproductive hormone levels in women. Epilepsy Behav 4:407-13. Houser CR (1990) Granule cell dispersion in the dentate gyrus of...cortex from epileptic patients. Neurobiol Dis 8:459- 68. Kostarczyk EM (1986) The amygdala and male reproductive functions. I. Anatomical and

Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress.

PubMed

Kennedy, David O; Little, Wendy; Haskell, Crystal F; Scholey, Andrew B

2006-02-01

Melissa officinalis (lemon balm) and Valeriana officinalis (valerian) have been used both traditionally and contemporaneously as mild sedatives, anxiolytics and hypnotics. Recent research has suggested that both may attenuate laboratory induced stress. As the two herbs are most often sold in combination with each other the current study assessed the anxiolytic properties of such a combination during laboratory-induced stress. In this double-blind, placebo-controlled, randomized, balanced cross-over experiment, 24 healthy volunteers received three separate single doses (600 mg, 1200 mg, 1800 mg) of a standardized product containing M. officinalis and V. officinalis extracts, plus a placebo, on separate days separated by a 7 day wash out period. Modulation of mood and anxiety were assessed during pre-dose and 1 h, 3 h and 6 h post-dose completions of a 20 min version of the Defined Intensity Stressor Simulation (DISS) battery. Cognitive performance on the four concurrent tasks of the battery was also assessed. The results showed that the 600 mg dose of the combination ameliorated the negative effects of the DISS on ratings of anxiety. However, the highest dose (1800 mg) showed an increase in anxiety that was less marked but which reached significance during one testing session. In addition, all three doses led to decrements in performance on the Stroop task module within the battery, and the two lower doses led to decrements on the overall score generated on the DISS battery. These results suggest that a combination of Melissa officinalis and Valeriana officinalis possesses anxiolytic properties that deserve further investigation. Copyright 2006 John Wiley & Sons, Ltd.

Optic nerve head blood flow response to reduced ocular perfusion pressure by alteration of either the blood pressure or intraocular pressure.

PubMed

Wang, Lin; Cull, Grant A; Fortune, Brad

2015-04-01

To test the hypothesis that blood flow autoregulation in the optic nerve head has less reserve to maintain normal blood flow in the face of blood pressure-induced ocular perfusion pressure decrease than a similar magnitude intraocular pressure-induced ocular perfusion pressure decrease. Twelve normal non-human primates were anesthetized by continuous intravenous infusion of pentobarbital. Optic nerve blood flow was monitored by laser speckle flowgraphy. In the first group of animals (n = 6), the experimental eye intraocular pressure was maintained at 10 mmHg using a saline reservoir connected to the anterior chamber. The blood pressure was gradually reduced by a slow injection of pentobarbital. In the second group (n = 6), the intraocular pressure was slowly increased from 10 mmHg to 50 mmHg by raising the reservoir. In both experimental groups, optic nerve head blood flow was measured continuously. The blood pressure and intraocular pressure were simultaneously recorded in all experiments. The optic nerve head blood flow showed significant difference between the two groups (p = 0.021, repeat measures analysis of variance). It declined significantly more in the blood pressure group compared to the intraocular pressure group when the ocular perfusion pressure was reduced to 35 mmHg (p < 0.045) and below. There was also a significant interaction between blood flow changes and the ocular perfusion pressure treatment (p = 0.004, adjusted Greenhouse & Geisser univariate test), indicating the gradually enlarged blood flow difference between the two groups was due to the ocular perfusion pressure decrease. The results show that optic nerve head blood flow is more susceptible to an ocular perfusion pressure decrease induced by lowering the blood pressure compared with that induced by increasing the intraocular pressure. This blood flow autoregulation capacity vulnerability to low blood pressure may provide experimental evidence related to the

Sleep disturbances and exposure to organic solvents

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

Lindelof, B.; Almkvist, O.; Goethe, C.

An inquiry about sleep habits and sleep disturbances revealed a significantly higher prevalence of insomnia in a solvent-exposed group than in a comparable group that had no occupational exposure to organic solvents. The solvent-exposed group has also registered an increased consumption of hypnotics, and a significant increase occurred in the number of individuals who had consulted physicians because of sleep disorders. The results indicate that solvent exposure could induce sleep disturbances.

Impact of a preoperative conversational hypnotic session on propofol consumption using closed-loop anesthetic induction guided by the bispectral index

PubMed Central

Bataille, Aurélien; Besset, Sébastien; Szekely, Barbara; Michel-Cherqui, Mireille; Dumans, Virginie; Liu, Ngai; Chazot, Thierry; Fischler, Marc; Le Guen, Morgan

2017-01-01

the effect of a hypnotic conversational session on anesthesia induction using an automated tool for propofol administration. PMID:28489735

The special effects of hypnosis and hypnotherapy: A contribution to an ecological model of therapeutic change.

PubMed

Mende, Matthias

2006-04-01

There is ample evidence that hypnosis enhances the effectiveness of psychotherapy and produces some astounding effects of its own. In this paper, the effective components and principles of hypnosis and hypnotherapy are analyzed. The "special" hypnotic and hypnotherapeutic effects are linked to the fact that the ecological requirements of therapeutic change are taken into account implicitly and/or explicitly when working with hypnotic trances in a therapeutic setting. The hypnotic situation is described--theoretically and in case examples--as a therapeutic modality that gratifies and aligns the basic emotional needs to feel autonomous, related, competent, and oriented. It is shown how the hypnotic relationship can help promote a sound ecological balance between these needs--a balance that is deemed to be a necessary prerequisite for salutogenesis. Practical implications for planning hypnotherapeutic interventions are discussed.

The effects of perphenazine on self-administration behavior.

PubMed

Johanson, C E; Kandel, D A; Bonese, K

1976-04-01

In Experiment 1.6 rhesus monkeys prepared with intravenous catheters responded on a fixed-ratio 10 schedule for either an injection of 0.2 mg/kg of cocaine or 0.5 mg/kg of pentobarbital during a daily 3 hr session. The substitution of saline or various doses of perphenazine resulted in very low rates of responding. These results indicate that perphenazine is not a positive reinforcer. Pretreating animals maintained on 0.1 mg/kg or 0.2 mg/kg of cocaine with perphenazine resulted in increases in rate of self-administration at some doses and a decrease in rate at higher doses. The dose of perphenazine which resulted in the maximal increase in cocaine self-administration was directly related to the dose of cocaine maintaining responding. Pretreating animals maintained on 0.5 mg/kg of pentobarbital with perphenazine had no effect at doses which increased cocaine self-administration but decreased rate of pentobarbital self-administration at higher doses. These results indicate that perphenazine is capable of antagonizing some of the effects of cocaine.

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Vol. 47/No. RR-4.

DTIC Science & Technology

1998-04-17

antihista- mines (e.g., astemizole or terfenadine); sedative-hypnotics (e.g., alprazolam , midazolam, or triazolam); calcium channel blockers (e.g...acetate, propafenone, or quinidine); ergot alkaloid derivatives; cisapride; sedative-hypnotics (e.g., alprazolam , clorazepate, diazepam, estazo- lam

THE EFFECTS OF IONIZING RADIATIONS ON THE BIOCHEMISTRY OF MAMMALIAN TISSUES. III. STUDIES ON THE TOXICITY AND MECHANISM OF ACTION OF 2-MERCAPTOETHYLAMINE

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

Hietbrink, B.E.; Yam, K.M.

1964-10-31

A study was conducted to determine the effect of dibenzyline, dihydroergotamine, and adrenal demedullation on the mercaptoethylamine-induced increase in the blood glucose level of adult female rats. The results of these studies showed that the administration of dibenzyline or dihydroergotamine 10 min before 200 mg/kg of MEA inhibited the marked increase in blood glucose levels usually observed following this dose of MEA and substantially reduced the duration of action of this sulfur-containing compound. Adrenal demedullation almost completely prevented the increase in blood glucose levels caused by 200 mg/ kg of MEA. MEA caused a marked hypoglycemia in the demedullated animalsmore » during the latter part of the 5-hr observation period. Results of experiments on the influence of chronic administration of MEA on the blood glucose level of the rat indicated that repeated doses of MEA do not appear to cause drug tolerance. Studies on the influence of MEA on the acetylcholinesterase activity of the brain and serum of rats indicated that the gross toxic symptoms observed following the administration of MEA were not due to cholinesterase inhibition. The results of preliminary studies on the influence of sodium pentobarbital on the acute toxicity of MEA indicated that 25 mg/kg of pentobarbital prevented the lethal effect of doses of MEA as great as 325 mg/kg. (auth)« less

Comparison of tizanidine and morphine with regard to tolerance-developing ability to antinociceptive action.

PubMed

Nabeshima, T; Yamada, S; Sugimoto, A; Matsuno, K; Kameyama, T

1986-10-01

The antinociceptive, tolerance-developing and anti-withdrawal activities of tizanidine [5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzo-thiadiazole] were investigated by comparing its effects with those of morphine and clonidine in tail-flick-, hot plate-, acetic acid-induced writhing-, and naloxone-precipitated withdrawal jumping-tests. The antinociceptive action of tizanidine was not altered by naloxone, while that of morphine was antagonized. Tolerance to the tizanidine-induced antinociceptive action and to motor incoordination was developed by successive administration of tizanidine. In the tizanidine-tolerant mice, the antinociceptive action of morphine was significantly decreased, but not sleeping time induced by pentobarbital. The action of tizanidine was not modified in the morphine-tolerant mice. Tizanidine failed to induce morphine-withdrawal jumping and to inhibit naloxone-precipitated withdrawal jumping in the morphine-dependent mice. Cross tolerance to the antinociceptive action induced by tizanidine and clonidine was developed. These results suggest that alpha 2-adrenoreceptors may be involved in the action mechanism of tizanidine, but not opioid receptors. Functional tolerance to tizanidine action may be developed by successive administration of tizanidine.

Modulation of type I immediate and type IV delayed immunoreactivity using direct suggestion and guided imagery during hypnosis.

PubMed

Zachariae, R; Bjerring, P; Arendt-Nielsen, L

1989-11-01

Cutaneous reactivity against histamine skin prick test (Type I) and purified tuberculin protein derivative (Mantoux reaction, Type IV) was studied in eight volunteers under hypnosis. Types I and IV immunoreactivity were modulated by direct suggestion (Type I) and guided imagery (Type IV). The volunteers were highly susceptible subjects, selected by means of the Harvard Group Scale of Hypnotic Susceptibility, Form A. When the volunteers underwent hypnotic suggestion to decrease the cutaneous reaction to histamine prick test, a significant (P less than 0.02) reduction of the flare reaction (area of erythema) was observed compared with control histamine skin prick tests. The wheal reaction did not respond to hypnotic suggestion. Neither wheal nor flare reaction could be increased in size by hypnotic suggestion compared with control histamine skin prick tests. A hypnotic suggestion of increasing the Type IV reaction on one arm and decreasing the reaction on the other revealed a significant difference in both erythema size (P less than 0.02) and palpable induration (P less than 0.01). In two cases the reactions were monitored by laser doppler blood flowmetry and skin thickness measurement by ultrasound. The difference between the suggested increased and decreased reaction was 19% for the laser doppler bloodflow (in favor of the augmented side), and 44% for the dermal infiltrate thickness. This study objectively supports the numerous uncontrolled case reports of modulation of immunoreactivity in allergic diseases involving both Type I and Type IV skin reactions following hypnotic suggestions.

Crime and hypnosis in fin-de-siècle Germany: the Czynski case

PubMed Central

Wolffram, Heather

2017-01-01

Lurid tales of the criminal use of hypnosis captured both popular and scholarly attention across Europe during the closing decades of the nineteenth century, culminating not only in the invention of fictional characters such as du Maurier's Svengali but also in heated debates between physicians over the possibilities of hypnotic crime and the application of hypnosis for forensic purposes. The scholarly literature and expert advice that emerged on this topic at the turn of the century highlighted the transnational nature of research into hypnosis and the struggle of physicians in a large number of countries to prise hypnotism from the hands of showmen and amateurs once and for all. Making use of the 1894 Czynski trial, in which a Baroness was putatively hypnotically seduced by a magnetic healer, this paper will examine the scientific, popular and forensic tensions that existed around hypnotism in the German context. Focusing, in particular, on the expert testimony about hypnosis and hypnotic crime during this case, the paper will show that, while such trials offered opportunities to criminalize and pathologize lay hypnosis, they did not always provide the ideal forum for settling scientific questions or disputes.

Annual Progress Report on the Research Program of the United States Army Medical Research Institute of Infectious Diseases on Medical Defense against Biological Agents for Fiscal Year 1981

DTIC Science & Technology

1981-10-01

R. Di Luzio. 1980. Glucan -induced enhancement of host resistance to selected infectious diseases. Infect. Immun. 30:51-57. 3. Vezza, A. C., P. Cash...pathway of beta -oxidation to produce ketones. When infused as a 3 or 6% solution along with the 48% branched-chaia mixture, this compound had a hypnotic...dent Staff Physician 27:37-42. 9. Beisel, W. R. 1981. Impact of infectious disease upon fat metabolism and immune functions. Cancer Res. 41:3797-3798

Effect of a Hypocretin/Orexin Antagonist on Neurocogniive Performance

DTIC Science & Technology

2014-09-01

time: Tuesday , Nov 12, 2013, 4:00 PM - 5:00 PM Topic: ++E.08.e Sleep: Systems and behavior Authors: W. LINCOLN1, J. PALMERSTON1, T. NEYLAN2, T...functional impairment results from HcrtR antagonist-induced sleep, we evaluated the performance of rats in the Morris Water Maze in the presence of ALM vs. ZOL... Morris Water Maze. Although the concentrations of ALM and ZOL adminis- tered prior to these tests were equipotent in hypnotic efficacy, the

Abrupt treatments of hysteria during World War I, 1914-18.

PubMed

Macleod, Ad Sandy

2018-06-01

Case reports of the abrupt recovery of hysterical disorders during World War I (1914-18), though undoubtedly subject to publication bias, raise both aetiological and treatment issues regarding pseudo-neurological conversion symptoms. Published clinical anecdotes report circumstantial, psychotherapeutic, hypnotic, persuasive (and coercive) methods seemingly inducing recovery, and also responses to fright and alterations of consciousness. The ethics of modern medical practice would not allow many of these techniques, which were reported to be effective, even in the chronic cases.

The Possible Role of Hypnosis in Homograft Retention

PubMed Central

Fogel, Sydney; Knight, Charles R.

1965-01-01

Hypnosis was used to alter body image in an attempt to enable a woman to retain a skin homograft from an unrelated male donor. The man also acted as a nonhypnotized control by receiving a homograft from the hypnotized woman. Oneinch square full-thickness skin homografts were exchanged between the upper arms of the two volunteers. The homograft on the arm of the woman is still viable after eight months; the homograft on the man was rejected within two weeks. A second experiment in which the same subject was told under hypnosis to reject the homograft failed to produce rejection. Definite conclusions are not yet justified. Among factors to be considered in the present case are an unusual compatibility, schizophrenia as an inhibitor of the rejection mechanism, hypnotically induced irreversible acceptance, or other unknown mechanisms. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15 PMID:14339293

Pharmacology of Ramelteon, a Selective MT1/MT2 Receptor Agonist: A Novel Therapeutic Drug for Sleep Disorders

PubMed Central

Miyamoto, Masaomi

2009-01-01

An estimated one-third of the general population is affected by insomnia, and this number is increasing due to more stressful working conditions and the progressive aging of society. However, current treatment of insomnia with hypnotics, gamma-aminobutyric acid A (GABAA) receptor modulators, induces various side effects, including cognitive impairment, motor disturbance, dependence, tolerance, hangover, and rebound insomnia. Ramelteon (Rozerem; Takeda Pharmaceutical Company Limited, Osaka, Japan) is an orally active, highly selective melatonin MT1/MT2 receptor agonist. Unlike the sedative hypnotics that target GABAA receptor complexes, ramelteon is a chronohypnotic that acts on the melatonin MT1 and MT2 receptors, which are primarily located in the suprachiasmatic nucleus, the body's “master clock.” As such, ramelteon possesses the first new therapeutic mechanism of action for a prescription insomnia medication in over three decades. Ramelteon has demonstrated sleep-promoting effects in clinical trials, and coupled with its favorable safety profile and lack of abuse potential or dependence, this chronohypnotic provides an important treatment option for insomnia. PMID:19228178

Evaluation of CNS activities of aerial parts of Cynodon dactylon Pers. in mice.

PubMed

Pal, Dilipkumar

2008-01-01

The dried extracts of aerial parts of Cynodon dactylon Pers. (Graminae) were evaluated for CNS activities in mice. The ethanol extract of aerial parts of C. dactylon (EECD) was found to cause significant depression in general behavioral profiles in mice. EECD significantly potentiated the sleeping time in mice induced by standard hypnotics viz. pentobarbitone sodium, diazepam, and meprobamate in a dose dependant manner. EECD showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. EECD inhibited the onset and the incidence of convulsion in a dose dependent manner against pentylenetetrazole (PTZ)-induced convulsion. The present study indicates that EECD has significant CNS depressant activities.

Direct Activation of Sleep-Promoting VLPO Neurons by Volatile Anesthetics Contributes to Anesthetic Hypnosis

PubMed Central

Moore, Jason T; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C; Beck, Sheryl G; Kelz, Max B

2013-01-01

Summary Background Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Results Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, while neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized, but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Conclusions Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. PMID:23103189

Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetic hypnosis.

PubMed

Moore, Jason T; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C; Beck, Sheryl G; Kelz, Max B

2012-11-06

Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, whereas neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

Contextual mediation of perceptions in hauntings and poltergeist-like experiences.

PubMed

Lange, R; Houran, J; Harte, T M; Havens, R A

1996-06-01

The content of perceived apparitions, e.g., bereavement hallucinations, cannot be explained entirely in terms of electromagnetically induced neurochemical processes. It was shown that contextual variables influential in hallucinatory and hypnotic states also structured reported haunting experiences. As predicted, high congruency was found between the experiential content and the nature of the contextual variables. Further, the number of contextual variables involved in an experience was related to the type of experience and the state or arousal preceding the experience. Based on these findings we argue that a more complete explanation of haunting experiences should take into account both electromagnetically induced neurochemical processes and factors related to contextual mediation.

The effect of inhibitors of endogenous opioid degradation, bacitracin, bestatin, captopril, and D-phenylalanine, on digoxin-induced arrhythmias in guinea pigs.

PubMed

Rabkin, S W; Redston, M

1989-08-01

The purpose of this study was to investigate the effect of inhibition of endogenous opioid degradation on digitalis-induced arrhythmias, utilizing the inhibitors bacitracin, bestatin, captopril, and D-phenylalanine. Guinea pigs, anesthetized with pentobarbital, 50 mg/kg i.p., and breathing spontaneously received intracerebroventricular (i.c.v.) injection of bacitracin (6.8 mg/kg), bestatin (1 mg/kg), captopril (2 mg/kg), D-phenylalanine (1.2 mg/kg) or the diluent, saline. Digitalis arrhythmias were induced by a 50 micrograms/kg i.v. bolus of digoxin followed by 500 micrograms.kg-1.h-1 i.v. Bacitracin and bestatin, but not captopril or D-phenylalanine, significantly (p less than 0.05) altered the relationship between the digoxin dose and the first occurrence of arrhythmias, i.e., digoxin-induced ventricular arrhythmias became manifest at lower digoxin doses. The mean digoxin dose and ED50s, at which arrhythmias first occurred, were significantly (p less than 0.05) reduced by bacitracin and bestatin. The findings were similar for fatal arrhythmias, although D-phenylalanine appeared to decrease the digoxin dose at the development of fatal arrhythmias. The opioid antagonist naloxone, in a 50 micrograms/kg bolus and 50 micrograms.kg-1.h-1 i.c.v., completely prevented these effects of bacitracin and reduced the effect of bestatin. The relationship to arrhythmias could not be ascribed to an effect on blood pressure, as the blood pressure response to digoxin was the same in bestatin, D-phenylalanine, and control groups. To examine whether systemic administration of an inhibitor of opioid degradation had similar effects, a second protocol was selected with systemic administration of bacitracin because it altered the dose effect relationship after i.c.v. administration and systemic concentrations could be readily attained. Bacitracin, in a 13.5 mg/kg i.v. bolus and 135 mg.kg-1.h-1 i.v., was followed by 100 micrograms/kg digoxin i.v. every 15 min.(ABSTRACT TRUNCATED AT 250

Chemical characterization and pharmacological assessment of polysaccharide free, standardized cashew gum extract (Anacardium occidentale L.).

PubMed

da Silva, Daiany Priscilla Bueno; Florentino, Iziara Ferreira; da Silva Moreira, Lorrane Kelle; Brito, Adriane Ferreira; Carvalho, Verônica Vale; Rodrigues, Marcella Ferreira; Vasconcelos, Géssica Adriana; Vaz, Boniek Gontijo; Pereira-Junior, Marcus Antônio; Fernandes, Kátia Flávia; Costa, Elson Alves

2018-03-01

The cashew gum (Anacardium occidentale L.) is used in traditional Brazilian medicine in the treatment of inflammatory conditions, asthma, diabetes, and gastrointestinal disturbances. In the present study, we aimed at forming a chemical characterization and investigation of the antinociceptive and anti-inflammatory activities of the aqueous extract of cashew gum without the presence of polysaccharides in its composition (CGE). The CGE was obtained after the precipitation and removal of polysaccharides through the use of acetone. After, the acetone was removed by rotaevaporation, and the concentrated extract was lyophilized. The chemical characterization of CGE was performed by liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS/MS) analyses. Mice were used for the evaluation of the antinociceptive and anti-inflammatory activities. CGE was analyzed via the Irwin test, acetic acid-induced writhing test, formalin-induced pain test, and carrageenan-induced paw edema test. The motor activity or probable sedation was verified through the chimney, open-field, and sodium pentobarbital-induced sleep tests. We investigated if the analgesic and anti-inflammatory effects of CGE depend of reduction in PGE 2 levels, were performed the carrageenan or PGE 2 -induced hyperalgesia tests. The chemical characterization of CGE showed the presence of anacardic acids as the predominant phytoconstituents. The treatment with CGE (75, 150, and 300mg/kg, p.o.) inhibited the number of writhing in a dose-dependent manner. With an intermediate dose, CGE did not cause motor impairment with the chimney test or alterations in either the open-field or sodium pentobarbital-induced sleep. In the formalin-induced pain test, CGE (150mg/kg, p.o.) produced an antinociceptive effect only in the first phase of the test, suggesting anti-inflammatory activity. With the same dosage, CGE also reduced the carrageenan-induced paw edema at all hours of the test, confirming its anti

[Effects of extracts from ziziphi spinosae semen and schisandrae chinensis fructus on amino acid neurotransmitter in rats with insomnia induced by PCPA].

PubMed

Gao, Jia-Rong; Ji, Wen-Bo; Jiang, Hui; Chen, Jin-Feng

2013-10-01

To observe the effects of extract from Ziziphus Spinosa Semen and Schisandrae Chinensis Fructus on the content of amino acid neurotransmitter in the hypothalamus of insomnia rats induced by P-Chlorophenylalanine (PCPA) and its mechanism. The model of insomnia rats were established by PCPA intraperitoneal injection, after the modeling, all the therapeutic group were treated with corresponding drug for one week. The hypothalamus pathological changes of the rats were observed. The contents of GABA, Glu in the hypothalamus were detected by Elisa. The GABA, Glu protein expression were detected by immunohistochemical. GABA(A), R(alpha1) and GABA(A)R(gamma2) mRNA expressions were detected by RT-PCR. Compared with model group, the content of GABA in the hypothalamus of rats increased obviously in the alcohol-water group (P < 0.05 or P < 0.01), while the content of Glu decreased obviously (P < 0.05 or P < 0.01). The extract from Ziziphus Spinosae Semen and Schisandrae Chinensis Fructus has obviously Sedative-hypnotic effect. Its mechanism may be related to regulating the content of amino acid neurotransmitter in the hypothalamus of rats.

Charged anaesthetics alter LM-fibroblast plasma-membrane enzymes by selective fluidization of inner or outer membrane leaflets.

PubMed Central

Sweet, W D; Schroeder, F

1986-01-01

The functional consequences of the differences in lipid composition and structure between the two leaflets of the plasma membrane were investigated. Fluorescence of 1,6-diphenylhexa-1,3,5-triene(DPH), quenching, and differential polarized phase fluorimetry demonstrated selective fluidization by local anaesthetics of individual leaflets in isolated LM-cell plasma membranes. As measured by decreased limiting anisotropy of DPH fluorescence, cationic (prilocaine) and anionic (phenobarbital and pentobarbital) amphipaths preferentially fluidized the cytofacial and exofacial leaflets respectively. Unlike prilocaine, procaine, also a cation, fluidized both leaflets of these membranes equally. Pentobarbital stimulated 5'-nucleotidase between 0.1 and 5 mM and inhibited at higher concentrations, whereas phenobarbital only inhibited, at higher concentrations. Cationic drugs were ineffective. Two maxima of (Na+ + K+)-ATPase activation were obtained with both anionic drugs. Only one activation maximum was obtained with both cationic drugs. The maximum in activity below 1 mM for all four drugs clustered about a single limiting anisotropy value in the cytofacial leaflet, whereas there was no correlation between activity and limiting anisotropy in the exofacial leaflets. Therefore, although phenobarbital and pentobarbital below 1 mM fluidized the exofacial leaflet more than the cytofacial leaflet, the smaller fluidization in the cytofacial leaflet was functionally significant for (Na+ + K+)-ATPase. Mg2+-ATPase was stimulated at 1 mM-phenobarbital, unaffected by pentobarbital and slightly stimulated by both cationic drugs at concentrations fluidizing both leaflets. Thus the activity of (Na+ + K+)-ATPase was highly sensitive to selective fluidization of the leaflet containing its active site, whereas the other enzymes examined were little affected by fluidization of either leaflet. PMID:3028369

Regression: A Bibliography.

ERIC Educational Resources Information Center

Pedrini, D. T.; Pedrini, Bonnie C.

Regression, another mechanism studied by Sigmund Freud, has had much research, e.g., hypnotic regression, frustration regression, schizophrenic regression, and infra-human-animal regression (often directly related to fixation). Many investigators worked with hypnotic age regression, which has a long history, going back to Russian reflexologists.…

Hypnosis and Rational-Emotive Therapy as Used in Teaching Improved Auto Suggestion.

ERIC Educational Resources Information Center

DeRoos, Yosikazu Spencer; Johnson, David Pittman

1983-01-01

Detailes a method incorporating hypnosis and Rational-Emotive Therapy (RET) into a procedure termed Rational-Emotive Hypnosis. Indicates several areas in which clients often have difficulty engaging successfully in RET, and offers hypnotic techniques to overcome such problems. Both direct and indirect hypnotic procedures are examined. (JAC)

[Use of hypnosis in the treatment of combat post traumatic stress disorder (PTSD)].

PubMed

Abramowitz, Eitan G; Bonne, Omer

2013-08-01

Clinical reports and observations going back almost two centuries consistently indicate that hypnotherapy is an effective modality for the treatment of post traumatic stress disorder (PTSD). Pierre Janet was the first clinician to describe the successful initiation of stepwise hypnotic techniques in PTSD symptom reduction. Hypnotherapy may accelerate the formation of a therapeutic alliance and contribute to a positive treatment outcome. Hypnotic techniques may be valuable for patients with PTSD who exhibit symptoms such as anxiety, dissociation, widespread somatoform pain complaints and sleep disturbances. Hypnotic techniques may also facilitate the arduous tasks of working through traumatic memories, increasing coping skills, and promoting a sense of competency. In this review we will present guidelines for the stepwise implementation of hypnotherapy in PTSD. Since most data regarding the use of hypnotherapy in PTSD has been gathered from uncontrolled clinical observations, methodologically sound research demonstrating the efficacy of hypnotic techniques in PTSD is required for hypnotherapy to be officially added to the therapeutic armamentarium for this disorder.

Comparison of psychotropic prescriptions between oncology and cardiology inpatients: result from a pharmacy database in a teaching hospital in Malaysia.

PubMed

Ng, Chong Guan; Mohamed, Salina; Wern, Tai Yi; Haris, Azwa; Zainal, Nor Zuraida; Sulaiman, Ahmad Hatim

2014-01-01

To examine the prescription rates in cancer patients of three common psychotropic drugs: anxiolytic/ hypnotic, antidepressant and antipsychotic. In this retrospective cohort study, data were extracted from the pharmacy database of University Malaya Medical Center (UMMC) responsible for dispensing records of patients stored in the pharmacy's Medication Management and Use System (Ascribe). We analyzed the use of psychotropics in patients from the oncology ward and cardiology from 2008 to 2012. Odds ratios (ORs) were adjusted for age, gender and ethnicity. A total of 3,345 oncology patients and 8,980 cardiology patients were included. Oncology patients were significantly more often prescribed psychotropic drugs (adjusted OR: anxiolytic/hypnotic=5.55 (CI: 4.64-6.63); antidepressants=6.08 (CI: 4.83-7.64) and antipsychotics=5.41 (CI: 4.17-7.02). Non-Malay female cancer patients were at significantly higher risk of anxiolytic/hypnotic use. Psychotropic drugs prescription is common in cancer patients. Anxiolytic/hypnotic prescription rates are significantly higher in non-Malay female patients in Malaysia.

Suggestibility and negative priming: two replication studies.

PubMed

David, Daniel; Brown, Richard J

2002-07-01

Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

Neurotoxicological effects of cinnabar (a Chinese mineral medicine, HgS) in mice

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

Huang, C.-F.; Liu, S.-H.; Lin-Shiau, S.-Y.

2007-10-15

Cinnabar, a naturally occurring mercuric sulfide (HgS), has long been used in combination with traditional Chinese medicine as a sedative for more than 2000 years. Up to date, its pharmacological and toxicological effects are still unclear, especially in clinical low-dose and long-term use. In this study, we attempted to elucidate the effects of cinnabar on the time course of changes in locomotor activities, pentobarbital-induced sleeping time, motor equilibrium performance and neurobiochemical activities in mice during 3- to 11-week administration at a clinical dose of 10 mg/kg/day. The results showed that cinnabar was significantly absorbed by gastrointestinal (G-I) tract and transportedmore » to brain tissues. The spontaneous locomotor activities of male mice but not female mice were preferentially suppressed. Moreover, frequencies of jump and stereotype-1 episodes were progressively decreased after 3-week oral administration in male and female mice. Pentobarbital-induced sleeping time was prolonged and the retention time on a rotating rod (60 rpm) was reduced after treatment with cinnabar for 6 weeks and then progressively to a greater extent until the 11-week experiment. In addition, the biochemical changes in blood and brain tissues were studied; the inhibition of Na{sup +}/K{sup +}-ATPase activities, increased production of lipid peroxidation (LPO) and nitric oxide (NO) were found with a greater extent in male mice than those in female mice, which were apparently correlated with their differences in the neurological responses observed. In conclusion, these findings, for the first time, provide evidence of the pharmacological and toxicological basis for understanding the sedative and neurotoxic effects of cinnabar used as a Chinese mineral medicine for more than 2000 years.« less

Differential Effects of Hypnosis, Biofeedback Training, and Trophotropic Responses on Anxiety, Ego Strength, and Locus of Control.

ERIC Educational Resources Information Center

Hurley, John D.

1980-01-01

College students were randomly assigned to one of four groups: hypnotic treatment, biofeedback treatment, trophotropic treatment, and control. Results indicated hypnosis was more effective in lowering anxiety levels. With regard to increasing ego strength, both the hypnotic and biofeedback training groups proved to be significant. Presented at the…

Group Hypnotizability Of Inpatient Adolescents.

PubMed

Quant, Michael; Schilder, Steffanie; Sapp, Marty; Zhang, Bo; Baskin, Thomas; Arndt, Leah Rouse

2017-01-01

This study investigated group hypnotizability in 167 adolescents (ages 13-17) in an inpatient behavioral healthcare setting through use of the Waterloo-Stanford Group Scale, Form C. It also investigated the influence of hypnotic inductions on group hypnotizability. Adolescents were randomly assigned to either a group session of hypnosis (n = 84) with a hypnotic induction or a comparison "no-induction" group (n = 83) that received identical suggestions without a hypnotic induction. Adolescents' imaginative absorption and dissociation were measured to examine their influence on hypnotizability. A between-group comparison showed the induction condition had a significantly higher score than the no-induction group on both behavioral and subjective measures of hypnotizability.

The Use of Role Play in the Training of Hypnotherapy.

ERIC Educational Resources Information Center

Sanders, Shirley

A model has been developed for using role play in the supervision and training of hypnotherapy. Specific techniques can be role played by trainee and supervisor which can enable the trainee to develop skill and confidence in the use of hypnotic techniques. Hypnotic induction, listening, observing and providing feedback, relaxation,…

Antiemetics With Concomitant Sedative Use in Civil Aviation Pilot Fatalities: From 2000 to 2006

DTIC Science & Technology

2007-10-01

Unclassified Unclassified 13 Form DOT F 1700.7 (8-72) Reproduction of completed page authorized iii CONTENTS INTRODUCTION...sedative hypnotics , and ethanol. Antiemetics and drugs with antiemetic properties such as metoclopramide, diphenhydramine (a sedating...antihistamines, ethanol, barbiturates, serotonin modulators, and/or sedative- hypnotics . Antihistamines such as diphenhydramine are commonly used. The

Cimetidine enhancement of cyclophosphamide antitumour activity.

PubMed Central

Dorr, R. T.; Alberts, D. S.

1982-01-01

Male DBA2 mice were given 10(6) P-388 leukaemic cells i.p. and cimetidine (CMT) at 100 mg/kg 1 day for 10 days, or as a single 100 mg/kg injection 30 min before cyclophosphamide (CTX). CMT significantly prolonged the survival of groups of mice receiving 50, 100 and 200 mg/kg of CTX 3 days after tumour inoculation. Median survival increased by 5.5 days (P less than 0.05), 10 days (P less than 0.05) and 13 days (P less than 0.05) respectively. The addition of CMT had the effect of roughly doubling the CTX dose, without increasing the lethality. CMT produced the only long-term survival seen in the study (1-2/10) CMT alone had no apparent antitumour activity. CMT significantly prolonged mean pentobarbital sleep to 28.6-60 min vs only 10 min for phenobarbital treated mice. Both CMT regimens increased the plasma concentration time products for CTX-induced metabolites (NBP) by about 1.3 fold (in contrast to a 33% reduction with phenobarbital). On average the single-dose CMT regimen produced the greatest effect on survival, on pentobarbital sleep duration and on total NBP reactive species. Probable mechanisms for the CMT-CTX interaction include competitive microsomal enzyme inhibition and/or acutely depressed hepatic blood flow. Caution should be used in combining CMT with full doses of CTX and any other highly metabolized antineoplastic agents in man. PMID:7059463

76 FR 81979 - Manufacturer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... (2010) I Tetrahydrocannabinols (7370) I Methamphetamine (1105) II Pentobarbital (2270) II Nabilone (7379) II With regard to Gamma Hydroxybutyric Acid (2010), Tetrahydrocannabinols (7370), and Methamphetamine...

77 FR 19718 - Manufacturer of Controlled Substances; Notice of Registration, Norac Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

... (2010) I Tetrahydrocannabinols (7370) I Methamphetamine (1105) II Pentobarbital (2270) II Nabilone (7379) II With regard to Gamma Hydroxybutyric Acid (2010), Tetrahydrocannabinols (7370), and Methamphetamine...

Nitric oxide mediates the anticonvulsant effects of thalidomide on pentylenetetrazole-induced clonic seizures in mice.

PubMed

Payandemehr, Borna; Rahimian, Reza; Gooshe, Maziar; Bahremand, Arash; Gholizadeh, Ramtin; Berijani, Sina; Ahmadi-Dastgerdi, Mohammad; Aminizade, Mehdi; Sarreshte-Dari, Ali; Dianati, Vahid; Amanlou, Massoud; Dehpour, Ahmad Reza

2014-05-01

Thalidomide is an old glutamic acid derivative which was initially used as a sedative medication but withdrawn from the market due to the high incidence of teratogenicity. Recently, it has reemerged because of its potential for counteracting number of diseases, including neurodegenerative disorders. Other than the antiemetic and hypnotic aspects, thalidomide exerts some anticonvulsant properties in experimental settings. However, the underlying mechanisms of thalidomide actions are not fully realized yet. Some investigations revealed that thalidomide could elicit immunomodulatory or neuromodulatory properties by affecting different targets, including cytokines (such as TNF α), neurotransmitters, and nitric oxide (NO). In this regard, we used a model of clonic seizure induced by pentylenetetrazole (PTZ) in male NMRI mice to investigate whether the anticonvulsant effect of thalidomide is affected through modulation of the l-arginine-nitric oxide pathway or not. Injection of a single effective dose of thalidomide (10 mg/kg, i.p. or higher) significantly increased the seizure threshold (P<0.05). On the one hand, pretreatment with low and per se noneffective dose of l-arginine [NO precursor] (10, 30 and 60 mg/kg) prevented the anticonvulsant effect of thalidomide. On the other hand, NOS inhibitors [l-NAME and 7-NI] augmented the anticonvulsant effect of a subeffective dose of thalidomide (1 and 5 mg/kg, i.p.) at relatively low doses. Meanwhile, several doses of aminoguanidine [an inducible NOS inhibitor] (20, 50 and 100 mg/kg) failed to alter the anticonvulsant effect of thalidomide significantly. In summary, our findings demonstrated that the l-arginine-nitric oxide pathway can be involved in the anticonvulsant properties of thalidomide, and the role of constitutive nNOS is prominent in the reported neuroprotective feature. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of the foetal time to death in mice after application of direct and indirect euthanasia methods.

PubMed

Muñoz-Mediavilla, C; Cámara, J A; Salazar, S; Segui, B; Sanguino, D; Mulero, F; de la Cueva, E; Blanco, I

2016-04-01

Directive 2010/63/EU on the protection of animals used for scientific purposes requires that the killing of mammal foetuses during the last third of their gestational period should be accomplished through effective and humane methods. The fact that murine foetuses are resistant to hypoxia-mediated euthanasia renders the current euthanasia methods ineffective or humane for the foetuses when these methods are applied to pregnant female mice. We have assessed the time to death of foetuses after performing either indirect (dam euthanasia) or direct (via intraplacental injection--a new approach to euthanasia) euthanasia methods in order to determine a euthanasia method that is appropriate, ethical and efficient for the killing of mouse foetuses. The respective times to death of foetuses after performing the three most commonly used euthanasia methods (namely cervical dislocation, CO2inhalation and intraperitoneal sodium pentobarbital administration) were recorded. Absence of foetal heartbeat was monitored via ultrasound. We consider that the most effective and humane method of foetal euthanasia was the one able to achieve foetal death within the shortest possible period of time. Among the indirect euthanasia methods assessed, the administration of a sodium pentobarbital overdose to pregnant female mice was found to be the fastest for foetuses, with an average post-treatment foetal death of approximately 29.8 min. As for the direct euthanasia method assessed, foetal time to death after intraplacental injection of sodium pentobarbital was approximately 14 min. Significant differences among the different mouse strains employed were found. Based on the results obtained in our study, we consider that the administration of a sodium pentobarbital overdose by intraplacental injection to be an effective euthanasia method for murine foetuses. © The Author(s) 2015.

Intraperitoneal Administration of Ethanol as a Means of Euthanasia for Neonatal Mice (Mus musculus).

PubMed

de Souza Dyer, Cecilia; Brice, Angela K; Marx, James O

2017-05-01

The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of ethanol as "acceptable with conditions," and recent work confirmed that this method is appropriate for euthanizing adult mice, but neonatal mice have not been tested. To explore this method in neonatal mice, mouse pups (C57BL/6 and CD1, 162 total) were injected with 100% ethanol, a pentobarbital-phenytoin combination, or saline at 7, 14, 21, 28, or 35 d of age. Electrocardiograms, respiratory rates, and times to loss of righting reflex and death were recorded. Time to death (TTD) differed significantly between ethanol and pentobarbital-phenytoin at 7, 14, and 21 d and between ethanol groups at 7, 14, and 21 d compared with 35 d. The average TTD (± 1 SD) for ethanol-injected mice were: 7 d, 70.3 ± 39.8 min; 14 d, 51.7 ± 30.5 min; 21 d, 32.3 ± 20.8 min, 28 d, 14.0 ± 15.2; and 35 d, 4.9 ± 1.4. Mean TTD in pentobarbital-phenytoin-injected mice were: 7 d, 2.8 ± 0.4 min; 14 d, 2.9 ± 0.5 min; 21 d, 3.9 ± 1.2 min; 28 d, 3.9 ± 0.7 min; and 35 d, 4.4 ± 0.5. Although TTD did not differ between ethanol and pentobarbital-phenytoin at 28 d of age, the TTD in 3 of 12 mice was longer than 15 min after ethanol administration at this age. Therefore, ethanol should not be used as a method of euthanasia for mice younger than 35 d, because the criteria for humane euthanasia were met only in mice 35 d or older.

Anesthetic agent-specific effects on synaptic inhibition.

PubMed

MacIver, M Bruce

2014-09-01

Anesthetics enhance γ-aminobutyric acid (GABA)-mediated inhibition in the central nervous system. Different agents have been shown to act on tonic versus synaptic GABA receptors to different degrees, but it remains unknown whether different forms of synaptic inhibition are also differentially engaged. With this in mind, we tested the hypothesis that different types of GABA-mediated synapses exhibit different anesthetic sensitivities. The present study compared effects produced by isoflurane, halothane, pentobarbital, thiopental, and propofol on paired-pulse GABAA receptor-mediated synaptic inhibition. Effects on glutamate-mediated facilitation were also studied. Synaptic responses were measured in rat hippocampal brain slices. Orthodromic paired-pulse stimulation was used to assess anesthetic effects on either glutamate-mediated excitatory inputs or GABA-mediated inhibitory inputs to CA1 neurons. Antidromic stimulation was used to assess anesthetic effects on CA1 background excitability. Agents were studied at equieffective concentrations for population spike depression to compare their relative degree of effect on synaptic inhibition. Differing degrees of anesthetic effect on paired-pulse facilitation at excitatory glutamate synapses were evident, and blocking GABA inhibition revealed a previously unseen presynaptic action for pentobarbital. Although all 5 anesthetics depressed synaptically evoked excitation of CA1 neurons, the involvement of enhanced GABA-mediated inhibition differed considerably among agents. Single-pulse inhibition was enhanced by propofol, thiopental, and pentobarbital, but only marginally by halothane and isoflurane. In contrast, isoflurane enhanced paired-pulse inhibition strongly, as did thiopental, but propofol, pentobarbital, and halothane were less effective. These observations support the idea that different GABA synapses use receptors with differing subunit compositions and that anesthetics exhibit differing degrees of selectivity for

A Nonpharmacologic Method for Enhancing Sleep in PTSD

DTIC Science & Technology

2015-10-01

medications include: Alcohol (during intoxication or withdrawal); cannabis (during intoxication); hallucinogens (during intoxication), phencyclidine... medications are taken solely under appropriate medical supervision, this criterion is not considered to be met. SEDATIVE/ HYPNOTIC/ANX CANNABIS ...are taken solely under appropriate medical supervision, this criterion is not considered to be met. SEDATIVE/ HYPNOTIC/ANX CANNABIS STIMULANTS

[Involvement of distal fragment of chromosome 13 in the regulation of sensitivity to ethanol in mice].

PubMed

Bazovkina, D V; Kulikov, A V

2015-01-01

The role of the fragment 57-65 cM of mouse chromosome 13 was studied in the regulation of ethanol action on locomotor activity, anxiety and sensitivity to hypnotic and hypothermic effects of ethanol. We used male mice of recombinant lines AKR/J and AKR.CBA-D13Mit76C, differing only in this fragment. After acute administration of ethanol only AKR mice showed the increase in the length of traveled distance in the open-field test (p < 0.05), only the AKR.CBA-D13Mit76C mice demonstrated the increase the time spent in the center of open-field arena (p < 0.05). Intact animals of both lines did not differ in sleep duration and intensity of hypothermia induced by injections of high doses of ethanol. At the same time, long-term alcohol treatment led to the weakening of the hypnotic effect of ethanol in the males of both lines compared to intact animals (p < 0.01 for the AKR, p < 0.001 for AKR.CBA-D13Mit76C). Chronic alcoholization led to increased ethanol-induced hypothermia in AKR males compared to intact animals (p < 0.01) and did not affect the intensity of ethanol hypothermic effect in AKR.CBA-D13Mit76C mice. The results suggest the involvement of the distal fragment 57-65 cM of chromosome 13 in the mechanisms of ethanol action in mice.

Emerging anti-insomnia drugs: tackling sleeplessness and the quality of wake time.

PubMed

Wafford, Keith A; Ebert, Bjarke

2008-06-01

Sleep is essential for our physical and mental well being. However, when novel hypnotic drugs are developed, the focus tends to be on the marginal and statistically significant increase in minutes slept during the night instead of the effects on the quality of wakefulness. Recent research on the mechanisms underlying sleep and the control of the sleep-wake cycle has the potential to aid the development of novel hypnotic drugs; however, this potential has not yet been realized. Here, we review the current understanding of how hypnotic drugs act, and discuss how new, more effective drugs and treatment strategies for insomnia might be achieved by taking into consideration the daytime consequences of disrupted sleep.

Hypnosis for nausea and vomiting in cancer chemotherapy: a systematic review of the research evidence.

PubMed

Richardson, J; Smith, J E; McCall, G; Richardson, A; Pilkington, K; Kirsch, I

2007-09-01

To systematically review the research evidence on the effectiveness of hypnosis for cancer chemotherapy-induced nausea and vomiting (CINV). A comprehensive search of major biomedical databases including MEDLINE, EMBASE, ClNAHL, PsycINFO and the Cochrane Library was conducted. Specialist complementary and alternative medicine databases were searched and efforts were made to identify unpublished and ongoing research. Citations were included from the databases' inception to March 2005. Randomized controlled trials (RCTs) were appraised and meta-analysis undertaken. Clinical commentaries were obtained. Six RCTs evaluating the effectiveness of hypnosis in CINV were found. In five of these studies the participants were children. Studies report positive results including statistically significant reductions in anticipatory and CINV. Meta-analysis revealed a large effect size of hypnotic treatment when compared with treatment as usual, and the effect was at least as large as that of cognitive-behavioural therapy. Meta-analysis has demonstrated that hypnosis could be a clinically valuable intervention for anticipatory and CINV in children with cancer. Further research into the effectiveness, acceptance and feasibility of hypnosis in CINV, particularly in adults, is suggested. Future studies should assess suggestibility and provide full details of the hypnotic intervention.

Experimental basis for a neurophysiological understanding of hypnoid states.

PubMed

Barolin, G S

1982-01-01

We postulate the hypnoid state of the human organism to be a third possible state besides waking and sleeping. This state can be equally induced by heterohypnotic and by autohypnotic means, by various techniques for meditation, relaxation and psychotherapy as well. It forms a basal status of the organism with partial deprivation of external stimuli. Out of this deprivation derives the possibility of stronger concentration on special stimuli (such as hypnotic suggestions) which would hence be able to act stronger in this state than in the waking state. Thus, it is possible to change external stimuli within their subjective perception (probably by ways of a subcortical modulating effect derived from the hypnotic suggestion). However, within their bioelectric parameters the stimuli pass unchanged through the peripheral receptor up to the cortex, which is measurable. If somebody produces actions within the hypnoid state these actions will have the same neurophysiological correlate as in the waking state, which means desynchronization. This does not exclude such actions (by concentration in the hypnoid state) having a stronger effect than in the waking state and/or having a different subjective perception.

Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study.

PubMed

Leufkens, T R M; Ramaekers, J G; de Weerd, A W; Riedel, W J; Vermeeren, A

2014-07-01

Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs. The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls). The study was conducted according to a 3 × 2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test. Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls. The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.

Hypnotic efficacy of zaleplon for daytime sleep in rested individuals.

PubMed

Whitmore, Jeffrey N; Fischer, Joseph R; Storm, William F

2004-08-01

The primary objective of this study was to determine whether zaleplon (10 mg) effectively promoted sleep during the daytime in well-rested individuals when compared to placebo. A secondary objective was to see if, while not expected, the use of zaleplon impacted the performance of well-rested individuals upon awakening. Repeated measures with 2 within-subject factors: drug (placebo/zaleplon) and trial (hourly testing during waking hours). Polysomnographic variables were recorded during a 3.5-hour nap following drug administration. Performance measures and subjective reports were collected during every waking trial of each session. The study was conducted at the Chronobiology and Sleep Laboratory located at Brooks Air Force Base. Twelve participants, 6 men and 6 women. 10-mg zaleplon or placebo capsules, single afternoon dose. Drug administration was counterbalanced and double-blinded. Zaleplon allowed participants to obtain significantly more slow-wave sleep than under placebo. There was also a trend for participants under zaleplon to accomplish a greater amount of sleep than under placebo. Performance was not adversely impacted following a 3.5-hour daytime sleep under zaleplon, nor were any undesirable symptoms induced. Zaleplon improves sleep quality when used by rested individuals to accomplish daytime sleep.

Rilmenidine produces mydriasis in cats by stimulation of CNS alpha 2-adrenoceptors.

PubMed

Koss, M C

2003-02-01

1. Experiments were undertaken to determine if the imidazoline/alpha2-adrenoceptor agonist, rilmenidine, would produce mydriasis in cats and, if so, to delineate its site of action and determine if this effect is mediated by imidazoline receptors or alpha2-adrenoceptors. 2. Rilmenidine produced dose-related pupillary dilator responses in pentobarbital anaesthetized cats that were independent of sympathetic innervation to the iris but were dependent upon intact parasympathetic neuronal tone. The ED50 for rilmenidine-induced pupillary dilation was approximately 200 microg kg(-1), i.v., and was sustained for at least 1 h. 3. The highly selective alpha2-adrenoceptor antagonist, RS-79948, administered either before or after rilmenidine, antagonized rilmenidine-induced mydriasis. Neuronally induced reflex inhibition of parasympathetic nerve activity was also inhibited by administration of RS-79948. 4. These results suggest that rilmenidine acts like clonidine to produce pupillary dilation by inhibition of parasympathetic tone to the iris sphincter and that this central nervous system parasympatho-inhibition is mediated by alpha2-adrenoceptors, rather than imidazoline receptors.

Neuropharmacological profile of ethnomedicinal plants of Guatemala.

PubMed

Morales Cifuentes, C; Gómez-Serranillos, M P; Iglesias, I; Villar del Fresno, A M; Morales, C; Paredes, M E; Cáceres, A

2001-08-01

We carried out the Irwin's test with some different extracts of the aerial parts of Thidax procumbens L., the leaves of Neurolaena lobata (L.) R. Br., bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp., and root and leaves of Petiveria alliacea L. At dosage of 1.25 g dried plant/kg weight aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp. demonstrated the most activity: decrease in motor activity, back tonus, reversible parpebral ptosis, catalepsy and strong hypothermia. These extracts of both plants were assayed for effects on CNS and they caused very significant reductions in spontaneous locomotor activity, exploratory behavior and rectal temperature and they increased the sodium pentobarbital-induced sleeping time.

21 CFR 522.1704 - Sodium pentobarbital injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... general anesthetic in dogs and cats. Although it may be used as a general surgical anesthetic for horses, it is usually given at a lower dose to cause sedation and hypnosis and may be supplemented with a local anesthetic. It may also be used in dogs for the symptomatic treatment of strychnine poisoning. (ii...

21 CFR 522.1704 - Sodium pentobarbital injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... general anesthetic in dogs and cats. Although it may be used as a general surgical anesthetic for horses... local anesthetic. It may also be used in dogs for the symptomatic treatment of strychnine poisoning. (ii) The drug is administered intravenously “to effect”. For general surgical anesthesia, the usual dose is...

21 CFR 522.1704 - Sodium pentobarbital injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... general anesthetic in dogs and cats. Although it may be used as a general surgical anesthetic for horses... local anesthetic. It may also be used in dogs for the symptomatic treatment of strychnine poisoning. (ii) The drug is administered intravenously “to effect”. For general surgical anesthesia, the usual dose is...

Anticonvulsive activity of Butea monosperma flowers in laboratory animals.

PubMed

Kasture, Veena S; Kasture, S B; Chopde, C T

2002-07-01

The bioassay-guided fractionation of dried flowers of Butea monosperma (BM) was carried out to isolate the active principle responsible for its anticonvulsant activity. The petroleum ether extract was fractionated by column chromatography using solvents of varying polarity such as n-hexane, n-hexane:ethyl acetate, ethyl acetate, and methanol. The anticonvulsive principle of B. monosperma was found to be a triterpene (TBM) present in the n-hexane:ethyl acetate (1:1) fraction of the petroleum ether extract. TBM exhibited anticonvulsant activity against seizures induced by maximum electroshock (MES) and its PD(50) was found to be 34.2+/-18.1 mg/kg. TBM also inhibited seizures induced by pentylenetetrazol (PTZ), electrical kindling, and the combination of lithium sulfate and pilocarpine nitrate (Li-Pilo). However, TBM was not effective against seizures induced by strychnine and picrotoxin. TBM exhibited depressant effect on the central nervous system. After repeated use for 7 days, the PD(50) (MES) of TBM increased to 51.5+/-12.1 mg/kg. Similarly, after repeated use of TBM, the duration of sleep induced by pentobarbital was not reduced significantly. Further studies are required to investigate its usefulness in the treatment of epilepsy.

Effects of angiotensin, vasopressin and atrial natriuretic peptide on intraocular pressure in anesthetized rats

NASA Technical Reports Server (NTRS)

Palm, D. E.; Shue, S. G.; Keil, L. C.; Balaban, C. D.; Severs, W. B.

1995-01-01

The effects of atrial natriuretic peptide (ANP), vasopressin (AVP) and angiotensin (ANG) on blood and intraocular pressures of pentobarbital anesthetized rats were evaluated following intravenous, intracerebroventricular or anterior chamber routes of administration. Central injections did not affect intraocular pressure. Equipressor intravenous infusions of ANG raised, whereas AVP decreased, intraocular pressure. Direct infusions of a balanced salt solution (0.175 microliter/min) raised intraocular pressure between 30 and 60 min. Adding ANG or ANP slightly reduced this solvent effect but AVP was markedly inhibitory. An AVP-V1 receptor antagonist reversed the blunting of the solvent-induced rise by the peptide, indicating receptor specificity. Acetazolamide pretreatment lowered intraocular pressure, but the solvent-induced rise in intraocular pressure and inhibition by AVP still occurred without altering the temporal pattern. Thus, these effects appear unrelated to aqueous humor synthesis rate. The data support the possibility of intraocular pressure regulation by peptides acting from the blood and aqueous humor.

Treating Panic Disorder Hypnotically.

PubMed

Reid, David B

2017-10-01

A hypnosis protocol for treating panic disorder is provided. The implementation of this protocol is demonstrated through a case example involving the successful treatment of a 28-year-old firefighter presenting with a 4-month history of near-daily panic attacks. Core principles associated with this protocol include: (1) Elementary education about the physiology of panic; (2) A review of primary factors contributing to the evolution and manifestation of panic; (3) Encouragement of physical activity; (4) Utilization of hypnosis applications; and (5) Monitoring and measuring progress evidenced by a reduction in the frequency and intensity of panic attacks. Six years after his last hypnosis session, "Jason," the once panicked firefighter returned to my office for concerns unrelated to panic, and reported that he remained panic-free, retained his job, and was twice promoted.

REVISITING THE SAFE PLACE:Method and Regulatory Aspects in Psychotherapy when Easing Allostatic Overload in Traumatized Patients.

PubMed

Gerge, Anna

2018-01-01

Safe-place inductions are considered important altered states of consciousness (ASC) to be (re)installed during trauma-informed psychotherapy. Coregulation aimed at changing implicit relational knowing and increasing integration and coherence through relational work and hypnotic techniques is crucial, as clients' abilities to self-soothe and regulate have become seriously impaired. Thus, resource-oriented metaphors as inner strength imagery is advocated. Also, methods such as creative-arts therapy and neurofeedback will induce ASCs, as most methods used with complex traumatized clients, due to their high hypnotizability. When positive or soothing imagery or relationally held suggestions for changed attentional focus are added to both psychodynamic psychotherapy and CBT, a hetero-hypnosis will be induced-a prerequisite for phase-specific trauma therapy aimed at changing inner schemas and scripts.

The state of the "state" debate in hypnosis: a view from the cognitive-behavioral perspective.

PubMed

Chaves, J F

1997-07-01

For most of the past 50 years, hypnosis research has been driven by a debate about whether hypnotic phenomena can be best described and understood as the product of an altered state of consciousness. The meanings of some of the pivotal concepts in this debate and the nature of the phenomena that gave rise to them were ambiguous at the outset and led to misconceptions and surplus meanings that have obscured the debate through most of its history. The nature of the posited hypnotic state and its assumed consequences have changed during this period, reflecting the abandonment of untenable versions of hypnotic state theory. Carefully conducted studies in laboratories around the world have refined our understanding of hypnotic phenomena and helped identify the critical variables that interact to elicit them. With the maturation of the cognitive-behavioral perspective and the growing refinement of state conceptions of hypnosis, questions arise whether the state debate is still the axis about which hypnosis research and theory pivots. Although heuristic value of this debate has been enormous, we must guard against the cognitive constraints of our own metaphors and conceptual frameworks.

The Effects of Hypnotherapy on Homosexuality

PubMed Central

Roper, Peter

1967-01-01

Fifteen homosexuals were treated with hypnosis. The patients were selected from a general psychiatric practice and had a long history of confirmed homosexual behaviour and showed no evidence of organic or psychotic illness. The type of hypnotic induction attempted in all cases is described. In those where a satisfactory depth of hypnotic trance was achieved a change in sexual orientation was suggested to the patient. Before therapy, each patient was assessed using the Kinsey scale. Results were evaluated in terms of the patient's subsequent behaviour and his subjective feelings. Of the 15 patients, three showed no improvement, four showed a mild improvement and eight showed a marked improvement. There was a significant correlation between the depth of hypnosis achieved and the therapeutic outcome. Those patients who reached a deep level of hypnotic trance were most likely to show a marked improvement. There were no significant correlations with other factors such as degree of homosexuality as measured on the Kinsey scale and the patient's marital status. Treatment of homosexuals with hypnosis may produce more satisfactory results than those obtainable by other means. The best results are likely to be achieved in patients who are good hypnotic subjects. PMID:6017544

Distinctive Recruitment of Endogenous Sleep-Promoting Neurons by Volatile Anesthetics and a Non-immobilizer

PubMed Central

Han, Bo; McCarren, Hilary S.; O'Neill, Dan; Kelz, Max B.

2014-01-01

BACKGROUND Numerous studies demonstrate that anesthetic-induced unconsciousness is accompanied by activation of hypothalamic sleep-promoting neurons, which occurs through both pre- and postsynaptic mechanisms. However, the correlation between drug exposure, neuronal activation, and onset of hypnosis remains incompletely understood. Moreover, the degree to which anesthetics activate both endogenous populations of GABAergic sleep-promoting neurons within the ventrolateral preoptic (VLPO) and median preoptic (MnPO) nuclei remains unknown. METHODS Mice were exposed to oxygen, hypnotic doses of isoflurane or halothane, or 1,2-dicholorhexafluorocyclobutane (F6), a nonimmobilizer. Hypothalamic brain slices prepared from anesthetic-naïve mice were also exposed to oxygen, volatile anesthetics, or F6 ex vivo, both in the presence and absence of tetrodotoxin. Double-label immunohistochemistry was performed to quantify the number of c-Fos-immunoreactive nuclei in the GABAergic subpopulation of neurons in the VLPO and the MnPO to test the hypothesis that volatile anesthetics, but not non-immobilizers, activate sleep-promoting neurons in both nuclei. RESULTS In vivo exposure to isoflurane and halothane doubled the fraction of active, c-Fos-expressing GABAergic neurons in the VLPO, while F6 failed to affect VLPO c-Fos expression. Both in the presence and absence of tetrodotoxin, isoflurane dose-dependently increased c-Fos expression in GABAergic neurons ex vivo, while F6 failed to alter expression. In GABAergic neurons of the MnPO, c-Fos expression increased with isoflurane and F6, but not with halothane exposure. CONCLUSIONS Anesthetic unconsciousness is not accompanied by global activation of all putative sleep-promoting neurons. However, within the VLPO hypnotic doses of volatile anesthetics, but not non-immobilizers, activate putative sleep-promoting neurons, correlating with the appearance of the hypnotic state. PMID:25057841

Ketamine-xylazine anesthesia causes hyperopic refractive shift in mice

PubMed Central

Tkatchenko, Tatiana V.; Tkatchenko, Andrei V.

2010-01-01

Mice have increasingly been used as a model for studies of myopia. The key to successful use of mice for myopia research is the ability to obtain accurate measurements of refractive status of their eyes. In order to obtain accurate measurements of refractive errors in mice, the refraction needs to be performed along the optical axis of the eye. This represents a particular challenge, because mice are very difficult to immobilize. Recently, ketamine-xylazine anesthesia has been used to immobilize mice before measuring refractive errors, in combination with tropicamide ophthalmic solution to induce mydriasis. Although these drugs have increasingly been used while refracting mice, their effects on the refractive state of the mouse eye have not yet been investigated. Therefore, we have analyzed the effects of tropicamide eye drops and ketamine-xylazine anesthesia on refraction in P40 C57BL/6J mice. We have also explored two alternative methods to immobilize mice, i.e. the use of a restraining platform and pentobarbital anesthesia. We found that tropicamide caused a very small, but statistically significant, hyperopic shift in refraction. Pentobarbital did not have any substantial effect on refractive status, whereas ketamine-xylazine caused a large and highly significant hyperopic shift in refraction. We also found that the use of a restraining platform represents good alternative for immobilization of mice prior to refraction. Thus, our data suggest that ketamine-xylazine anesthesia should be avoided in studies of refractive development in mice and underscore the importance of providing appropriate experimental conditions when measuring refractive errors in mice. PMID:20813132

Soybean meal fermented by Aspergillus awamori increases the cytochrome P-450 content of the liver microsomes of mice.

PubMed

Kishida, T; Ataki, H; Takebe, M; Ebihara, K

2000-04-01

The effect of soybean meal fermented by Aspergillus awamori on the acute lethality of acetaldehyde, pentobarbital sleeping time, and cytochrome P-450 content of the hepatic microsomes was studied in mice. Most of the daidzin and genistin in soybean meal (SBM) were converted into the respective aglycones, daidzein and genistein, by fermentation. In experiment 1, mice were fed isonitrogenic test diets with one of the following five protein sources for 28 d: casein, SBM, fermented and hot-air-dried SBM (FSBM-HD), fermented and freeze-dried SBM (FSBM-FD), or methanol-extracted FSBM-FD (FSMB-FD-R). The acute lethality of acetaldehyde in mice fed the FSBM-FD diet was significantly lower than that in mice fed the SBM, FSBM-HD, or FSBM-FD-R diet. In experiments 2 and 3, mice were fed isonitrogenic test diets with one of the following four protein sources for 28 d: casein, SBM, FSBM-FD, and FSBM-FD-R. The pentobarbital sleeping time was significantly shorter and the cytochrome P-450 content was significantly higher in the mice fed the FSBM-FD diet than the respective value in mice fed the other test diets. In experiment 4, mice were fed one of eight diets which contained different levels of aglycone obtained by varying the proportion of FSBM-FD and FSBM-FD-R, for 28 d. The cytochrome P-450 content in hepatic microsomes increased as the dietary level of isoflavonoid aglycones increased, but there was a saturation phenomenon. These results suggest that soy isoflavonoid aglycones are more potent inducers of cytochrome P-450 than isoflavonoid glycosides.

Sibutramine-associated psychotic symptoms and zolpidem-induced complex behaviours: implications for patient safety.

PubMed

Wiglusz, Mariusz S; Cubała, Wiesław Jerzy; Nowak, Paweł; Jakuszkowiak-Wojten, Katarzyna; Landowski, Jerzy; Krysta, Krzysztof

2013-09-01

Sibutramine is a weight loss agent recently withdrawn from the European market due to cardiovascular risk concerns. It was used for long-term obesity treatment. Zolpidem is a short acting hypnotic agent commonly used in the treatment of insomnia. A number of case reports describing psychotic reaction to sibutramine were reported in the literature. We present a case of a 61-year-old Caucasian woman who developed two psychotic episodes related to sibutramine treatment. The second psychotic episode was complicated with complex behaviours after zolpidem use due to insomnia. Sibutramine and zolpidem discontinuation resulted in rapid resolution of psychotic symptoms. This case suggests a possibility of incidence of psychotic symptoms and complex behaviour disturbances in patients prescribed sibutramine or other monoaminergic reuptake inhibitors.