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Ethanol Increases GABAergic Transmission and Excitability in Cerebellar Molecular Layer Interneurons from GAD67-GFP Knock-in Mice
published on December 20th, 2011 at 06:03 PM
Aims This study assessed the acute effect of ethanol on GABAergic transmission at molecular layer interneurons (MLIs; i.e. basket and stellate cells) in the cerebellar cortex. The actions of ethanol on spontaneous firing of these pacemaker neurons were also measured. Methods Transgenic mice (glutamic acid-decarboxylase 67-green fluorescent protein knock-in mice) that express green fluorescence protein in GABAergic interneurons were used to aid in the identification of MLIs. Parasagittal cerebellar slices were prepared and whole-cell patch-clamp electrophysiological techniques were used to measure GABAA receptor-mediated spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs). Loose-seal cell-attached recordings were used to measure spontaneous action potential firing. Results Stellate cells received spontaneous GABAergic input in the form of a mixture of action potential-dependent events (sIPSCs) and quantal events (mIPSCs); ethanol increased sIPSC frequency to a greater extent than mIPSC frequency. Ethanol increased spontaneous action potential firing of MLIs, which could explain the increase in sIPSC frequency in stellate cells. Basket cells received GABAergic input in the form of quantal events only. Ethanol significantly increased the frequency of these events, which may be mediated by a different type of interneuron (perhaps, the Lugaro cell) or Purkinje cell collaterals. Conclusions Ethanol exposure differentially increases GABA release at stellate cell vs. basket cell-to-Purkinje cell synapses. This effect may contribute to the abnormalities in cerebellar function associated with alcohol intoxication.
Ethanol Consumption Alters the Expression and Reactivity of Adrenomedullin in the Rat Mesenteric Arterial Bed
published on December 20th, 2011 at 06:03 PM
Aims: Adrenomedullin (AM) is a peptide that displays cardiovascular protective activity. We investigated the effects of chronic ethanol consumption on arterial blood pressure, vascular reactivity to AM and the expression of AM system components in the rat mesenteric arterial bed (MAB). Methods: Male Wistar rats were treated with ethanol (20% vol/vol) for 6 weeks. Systolic, diastolic and mean arterial blood pressure were monitored in conscious rats. Vascular reactivity experiments were performed on isolated rat MAB. Matrix metalloproteinase-2 (MMP-2) levels were determined by gelatin zymography. Nitrite and nitrate generation were measured by chemiluminescence. Protein and mRNA levels of pre-pro-AM, CRLR (calcitonin receptor-like receptor) and RAMP1, 2 and 3 (receptor activity-modifying proteins) were assessed by western blot and quantitative real-time polymerase chain reaction, respectively. Results: Ethanol consumption induced hypertension and decreased the relaxation induced by AM and acetylcholine in endothelium-intact rat MAB. Phenylephrine-induced contraction was increased in endothelium-intact MAB from ethanol-treated rats. Ethanol consumption did not alter basal levels of nitrate and nitrite, nor did it affect the expression of MMP-2 or the net MMP activity in the rat MAB. Ethanol consumption increased mRNA levels of pre-pro-AM and protein levels of AM in the rat MAB. Finally, no differences in protein levels or mRNA of CRLR and RAMP1, 2 and 3 were observed after treatment with ethanol. Conclusion: Our study demonstrates that ethanol consumption increases blood pressure and the expression of AM in the vasculature and reduces the relaxation induced by this peptide in the rat MAB.
Personality Traits and Coping Compensate for Disadvantageous Decision-making in Long-term Alcohol Abstinence
published on December 20th, 2011 at 06:03 PM
Aims: High relapse rate and extreme difficulty to maintain abstinence are core characteristics of alcohol dependence (AD). Previous studies have demonstrated a persistent decision-making (DM) deficit in AD. We aimed to reveal specific personality features and stress-coping mechanisms presumed to compensate for ineffective DM skills. Methods: Eighty-eight unmedicated patients with AD were enrolled. Intact general cognitive status was assured by IQ above 90. Forty-three patients had an average abstinence period of 12 weeks and were currently in an inpatient treatment program (short-term abstinence group, STA) and 45 patients were abstinent for at least 3 years (long-term abstinence group, LTA). The two groups were assessed using an integrative approach combining domains of DM, temperament and character dimensions and stress-coping measures. Results: Both groups performed at chance level with no linear improvement tendency on the gambling task assessing DM adequacy. The LTA group scored significantly higher on scales of self-directedness and cooperativeness. In contrast, levels of harm avoidance, emotion-oriented coping and perceived stress were significantly higher in the STA group. Conclusion: Our findings provide new evidence for a persistent DM deficit with no learning effect in AD. Despite the deficit, alcohol-dependent patients can achieve LTA. STA patients perceive higher levels of stress and use non-adaptive coping strategies. We propose that the more adaptive personality profile of LTA patients contributes to the compensation of the trait-like DM deficit in alcoholism. These compensatory features represent promising new targets for preventive measures and therapeutic interventions in AD.
Brief Alcohol Intervention by Newly Trained Workers Versus Leaflets: Comparison of Effect in Older Heavy Drinkers Identified in a Population Health Examination Survey: A Randomized Controlled Trial
published on December 20th, 2011 at 06:03 PM
Aims: To test if a brief motivational intervention (BMI) in a non-treatment seeking population of heavy drinkers results in a reduced alcohol intake. Methods: Screening of 12,364 participants in a Danish health examination survey led to 1026 heavy drinkers of whom 772 were included and randomized to a BMI group (n = 391) or a control group (n = 381) receiving two leaflets about alcohol. Follow-up took place after 6 and 12 months including 670 and 616 participants respectively. The outcome measure was self-reported weekly alcohol consumption. Data were analysed according to the intention-to-treat principle. We used the Motivational Interviewing Treatment Integrity 3.0 code (MITI) as a quality control of the interventions delivered. Results: The intervention effect of the BMI was –1.0 drinks/week, but the effect was not significant. The MITI analysis showed that the quality of the BMI delivered was sub-optimal, as only one of four aspects was above the recommended level for beginning proficiency. Conclusion: We found no effect of a BMI in reducing alcohol consumption. The generalizability of the study is questionable, as individuals with the lowest level of education, low income and unmarried individuals are under-represented.
Atypical Antipsychotic Drugs and Ethanol Withdrawal Syndrome: A Review
published on December 20th, 2011 at 06:03 PM
Aims: Alcoholism and psychosis are known to have common neurochemical substrates. The aim of this review is to assess the reports involved in the effects of some atypical antipsychotic agents on the signs of ethanol withdrawal syndrome (EWS) in rats. Thus, both effectiveness of these drugs in ethanol withdrawal and the association between the drug effects and the signs have been investigated here on the same animal model. Methods: Adult Wistar rats were used as subjects. Ethanol was given to rats by modified liquid diet technique for inducing ethanol dependence. Clozapine, olanzapine, risperidone, quetiapine and ziprasidone were the drugs tested. Effects of these drugs on the signs of ethanol withdrawal such as locomotor hyperactivity, stereotyped behavior, tremor, wet dog shakes, tail-stiffness, abnormal posture and gait, agitation and audiogenic seizures were evaluated for the first 6 h of ethanol withdrawal. Results: Although some beneficial effects of all the drugs on ethanol withdrawal signs were observed, olanzapine precipitated abnormal posture and gait in the animals. Effectiveness rank of the used atypical antipsychotics was as follows: risperidone = quetiapine > ziprasidone > klozapine > olanzapine. Conclusion: Our results suggest that risperidone and quetiapine seem to be potent and pharmacologically more active agents on EWS in rats. Thus, these drugs may be beneficial in treatment of EWS in patients with alcoholism. Ziprasidone and clozapine also seem to be useful drugs in treatment of ethanol withdrawal.
Mentorship for Alcohol Problems (MAP): A Peer to Peer Modular Intervention for Outpatients
published on December 20th, 2011 at 06:03 PM
Aims: This is a Stage I open pilot to develop a new intervention, Mentorship for Alcohol Problems (MAP), for individuals with alcohol-use disorders in community treatment programs. Methods: Ten mentors participated for 6 months until 30 mentees received MAP for 12 weeks. Behavioral and biological measures were conducted in addition to fidelity measures. Four focus groups were held with participants and clinician feedback surveys were completed. Results: Feasibility and acceptance data in the domains of patient interest, safety and satisfaction were promising. Mentees reduced their alcohol and substance use and the majority of mentors sustained abstinence. Fidelity measures indicated that mentors adhered to the delivery of treatment. Conclusion: MAP shows promise to be incorporated into professionally run outpatient alcohol treatment programs to assist in the reduction of alcohol and substance use.
Refractory Hypotension in a Patient with Wernicke's Encephalopathy
published on December 20th, 2011 at 06:03 PM
A 57-year-old male patient with gastric carcinoma underwent radical distal gastrectomy type II + Braun anastomosis, and received total parenteral nutrition for 10 days after surgery, followed by small amounts of semi-liquid nutrition for 3 days and liquid nutrition for 2 days. The patient developed refractory hypotension for more than 1 week in the early course of disease, and on Day 15 after surgery presented with characteristic signs of Wernicke's encephalopathy, including diplopia and mental confusion. The hypotension did not improve despite appropriate fluid replacement soon after admission. Treatment with moderate dose of thiamine for 3 months partly relieved ophthalmoplegia and confusion, but not Korsakoff syndrome. This extraordinary presentation with refractory hypotension and the unusual course of the disease encouraged us to present this case.
Do Media Messages Change People's Risk Perceptions for Binge Drinking?
published on December 20th, 2011 at 06:03 PM
Aims: The current study investigated the effect of a media health message for drinking on risk perception estimates (comparative optimism). Methods: Sixty-five young adults who regularly drink alcohol watched an anti-drinking scenario (having an accident due to drinking). There were two intervention conditions: 30 participants ‘imagined’ they were part of the scenario, and 35 ‘watched’ the scenario. They then completed four comparative optimism estimates comparing themselves to those the same age and gender with similar drinking habits. The four comparisons were of their likelihood of being involved in an accident due to drinking; having unprotected sex, when under the influence of alcohol; having a car accident due to drinking (drivers only) and developing cirrhosis. There was also a control group (n = 59) who just completed the questionnaires. Results: Both intervention groups reported significantly lower comparative optimism for accident, unprotected sex and car accident than the control group. The ‘imagine’ group reported significantly lower comparative optimism than the ‘watch’ group for accidents. Conclusions. These results highlighted that media messages can successfully change people's risk perception, and also that imagination can be a powerful tool in changing risk perceptions associated with binge drinking.
Social Norm Influences on Evaluations of the Risks Associated with Alcohol Consumption: Applying the Rank-Based Decision by Sampling Model to Health Judgments
published on December 20th, 2011 at 06:03 PM
Aims: The research first tested whether perceptions of other people's alcohol consumption influenced drinkers' perceptions of the riskiness of their own consumption. Second, the research tested how such comparisons are made—whether, for example, people compare their drinking to the ‘average’ drinker's or ‘rank’ their consumption amongst other people's. The latter untested possibility, suggested by the recent Decision by Sampling Model of judgment, would imply different cognitive mechanisms and suggest that information should be presented differently to people in social norm interventions. Methods: Study 1 surveyed students who provided information on (a) their own drinking, (b) their perceptions of the distribution of drinking in the UK and (c) their perceived risk of various alcohol-related disorders. Study 2 experimentally manipulated the rank of ‘target’ units of alcohol within the context of units viewed simultaneously. Results: In both studies, the rank of an individual's drinking in a context of other drinkers predicted perceptions of developing alcohol-related disorders. There was no evidence for the alternative hypothesis that people compared with the average of other drinkers' consumptions. The position that subjects believed they occupied in the ranking of other drinkers predicted their perceived risk, and did so as strongly as how much they actually drank. Conclusions: Drinking comparisons are rank-based, which is consistent with other judgments in social, emotional and psychophysical domains. Interventions should be designed to work with people's natural ways of information processing, through providing clients with information on their drinking rank rather than how their drinking differs from the average.
Normative Misperceptions about Alcohol Use in a General Population Sample of Problem Drinkers from a Large Metropolitan City
published on December 20th, 2011 at 06:03 PM
Aims: Heavy drinkers tend to overestimate how much others drink (normative fallacy), at least in college samples. Little research has been conducted to evaluate whether normative misperceptions about drinking extend beyond the college population. The present study explored normative misperceptions in an adult general population sample of drinkers. Methods: As part of a larger study, in Toronto, Canada, a random digit dialling telephone survey was conducted with 14,009 participants who drank alcohol at least once per month. Respondents with Alcohol Use Disorders Identification Test of eight or more (n = 2757) were asked to estimate what percent of Canadians of their same sex: (a) drank more than they do; (b) were abstinent and (c) drank seven or more drinks per week. Respondents' estimates of these population drinking norms were then compared with the actual levels of alcohol consumption in the Canadian population. Results: A substantial level of normative misperception was observed for estimates of levels of drinking in the general population. Estimates of the proportion of Canadians who were abstinent were fairly accurate. There was some evidence of a positive relationship between the respondents' own drinking severity and the extent of normative misperceptions. Little evidence was found of a relationship between degree of normative misperceptions and age. Conclusion: Normative misperceptions have been successfully targeted in social norms media campaigns as well as in personalized feedback interventions for problem drinkers. The present research solidifies the empirical bases for extending these interventions more widely into the general population.

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