Rationale-Laboratory paradigms are useful for investigating mechanisms of human alcohol cue reactivity in a highly controlled environment. A number of studies have examined the effects of beverage exposure or negative affective stimuli on cue reactivity independently, but only a few have reported on interaction effects between beverage cue and affective stimuli, and none have evaluated the effects of positive stimuli on beverage cue reactivity.Objectives-To assess independent and interactive effects of both positive and negative affective stimuli and beverage cue on psychophysiological and subjective measures of reactivity in alcohol dependence.Methods-A total of 47 non treatment-seeking paid volunteers with current alcohol dependence participated in a within-subjects trial where each was exposed to a standardized set of pleasant, neutral, or unpleasant visual stimuli followed by alcohol or water cues. Psychophysiological cue reactivity measures were obtained during beverage presentation, and subjective reactivity measures were taken directly following beverage presentation.Results-Mixed-effect models revealed a significant main effect of beverage and positive (but not negative) affective stimuli on subjective strength of craving, and significant main effects of both positive and negative affective stimuli on ratings of emotionality. Despite the power to detect relatively small interaction effects, no significant interactions were observed between affect and beverage conditions on any reactivity measure. A key finding of this study is that positive affective stimuli commonly associated with drinking situations can induce craving in the absence of alcohol cues.Conclusions-Main effects of beverage cue replicated results from previous studies. In addition, positive affective stimuli influenced craving strength. Beverage and affective cues showed no interaction effects.Communicating author: Dr. Barbara J. Mason, 10550 North Torrey Pines Road, TPC 5, La Jolla, CA 92037, phone (858-784-7324), fax (858-784-7340), and (mason@scripps.edu). Draft: Do not cite or quote without permission NIH Public Access Author Manuscript Psychopharmacology (Berl). Author manuscript; available in PMC 2009 October 6. Published in final edited form as:Psychopharmacology (Berl Alcohol cue reactivity models attempt to recreate in the laboratory risk conditions for relapse similar to those experienced by alcoholics in their natural environment (Niaura et al. 1988;Litt and Cooney 1999). These paradigms link exteroceptive (e.g. the sight and smell of alcohol) and/or interoceptive (e.g. mood) cues with a hypothesized internal motivational state to drink alcohol (Carter and Tiffany 1999;Litt and Cooney 1999), a state typically referred to as craving.Craving is often a target of pharmacological and cognitive-behavioral therapeutic interventions for alcoholics based on evidence suggesting that it may increase the likelihood of relapse among alcoholics following treatment (Monti et al. 1993a;Monti et al. 1993b;Rohsenow et al. 1994;Monti et al...

Acamprosate and naltrexone are therapeutically effective drugs that promote abstinence and prevent drinking relapse among alcohol-dependent patients, and dose-dependently decrease alcohol self-administration in animals. The purpose of this experiment was to investigate the behavioral specificity of acamprosate and naltrexone treatment in mice on alcohol drinking elicited in a schedule-induced polydipsia (SIP) task. Food-deprived male C57BL/6J (B6) mice were divided into three groups assigned to a 5% alcohol SIP, water SIP, or a 1-hour limited access regulatory water drinking task. Injections (intraperitoneal) of acute (0, 50, 100, 200, 400 mg/kg) and chronic (2 x 100 mg/kg, 10 days) acamprosate, or naltrexone (0, 1.0, 2.5, 5.0 mg/kg) were administered. Behavioral drug specificity was determined by comparing alterations in alcohol or water consumption in SIP with alterations in limited access drinking. Additionally, drug effects on drinking-specific measures (g/kg consumption and lick efficiency) were compared with those of non-drinking measures (head entries for food and locomotor activity) during SIP. In comparison with saline injections, acute acamprosate (400 mg/kg) reduced both alcohol and water drinking in both SIP and the regulatory drinking conditions, but had no significant effects on non-drinking measures. Chronic administration of acamprosate reduced both alcohol and water drinking during SIP, but did not significantly affect regulatory drinking or non-drinking measures. Naltrexone (1.0, 2.5, 5.0 mg/kg) reduced alcohol and water drinking in both paradigms, and at the highest dose, significantly reduced head entries for food. These results indicate that acamprosate (acute and chronic) and naltrexone are relatively non-selective in their effects on alcohol self-administration in this task.

New emphasis has been placed upon cerebellar research because of recent reports demonstrating involvement of the cerebellum in non-motor cognitive behaviors. Included in the growing list of cognitive functions associated with cerebellar activation is working memory. In this study, we explore the potential role of the cerebellum in spatial working memory using a mouse model of Purkinje cell loss. Specifically, we make aggregation chimeras between heterozygous lurcher (Lc/+) mutant embryos and +/+ (wildtype) embryos and tested them in the delayed matching-to-position (DMTP) task. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic gain-of-function mutation. Lc/+< ->+/+ chimeras therefore have Purkinje cells ranging from 0 to normal numbers. Through histological examination of chimeric mice and observations of motor ability, we showed that ataxia is dependent upon both the number and distribution of Purkinje cells in the cerebellum. In addition, we found that Lc/+ mice, with a complete loss of Purkinje cells, have a generalized deficit in DMTP performance that is probably associated with their motor impairment. Finally, we found that Lc/+< ->+/+ chimeric mice, as a group, did not differ from control mice in this task. Rather, surprisingly, analysis of their total Purkinje cells and performance in the DMTP task revealed a significant negative relationship between these two variables. Together, these findings indicate that the cerebellum plays a minor or indirect role in spatial working memory.

In addition to reducing alcohol drinking, both drugs had other behavioral effects that included reductions in regulatory drinking. These results suggest that the therapeutic utility of these drugs for ameliorating human alcohol addiction remains questionable.