Effect of positive and negative affective stimuli and beverage cues on measures of craving in non treatment-seeking alcoholics.

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. MATERIALS AND 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. CONCLUSIONS: 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. Main effects of beverage cue replicated results from previous studies. Beverage and affective cues showed no interaction effects.

Behavioral effects of aminoadamantane class NMDA receptor antagonists on schedule-induced alcohol and self-administration of water in mice.

RATIONALE: Aminoadamantanes represent a class of NMDA glutamate receptor antagonists that reduce alcohol consumption and may prevent alcohol-induced neuronal adaptations and side effects. OBJECTIVE: Behavioral specificity of memantine and amantadine on alcohol drinking in a schedule-induced polydipsia (SIP) task was investigated in mice. METHODS: Male C57BL/6J mice were food-deprived and divided into four groups: 5% alcohol SIP, water SIP, 1 h limited access regulatory water drinking, and a control group to determine if either drug altered ethanol drinking. Behavioral specificity of memantine (5, 10, and 25 mg/kg, ip) and amantadine (20, 40, and 60 mg/kg, ip) was determined by comparing alterations in alcohol or water consumption in SIP and regulatory water drinking. Drug effects on SIP drinking-specific measures (grams per kilogram consumption) were also compared to nondrinking measures (locomotion, head-entries for food, and lick efficiency). RESULTS: Compared to saline, memantine reduced alcohol SIP drinking (10 and 25 mg/kg). Memantine increased locomotion during alcohol SIP (25 mg/kg) and during water SIP (5 and 25 mg/kg). In contrast, amantadine reduced both alcohol SIP (40 mg/kg) and water SIP (40 and 60 mg/kg). Both drugs reduced regulatory water consumption over the entire dose range tested. Blood alcohol concentrations indicated consumption of physiologically meaningful amounts of alcohol during SIP, and that changes in alcohol metabolism did not account for drug-induced reductions in alcohol drinking. CONCLUSIONS: 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.

Schedule-induced alcohol drinking: non-selective effects of acamprosate and naltrexone.

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.