The effects of Acamprosate (the calcium salt of an acetylated form of homotaurine) and the benzodiazepine-receptor agonist Diazepam, were investigated on the alcohol-induced behavioural preference towards alcohol following chronic alcoholization by inhalation. We also examined the effects of Acamprosate and Diazepam on the blood alcohol level (BAL) and on the cortical microvascular network. Acamprosate (50, 100, 200 and 400 mg/kg daily per os during the alcoholization period) did not significantly reduce either BAL or alcohol-induced cortical hypervascularization. Increasing dosages of Acamprosate (i.e. 50, 100, and 200 mg/kg/day), however, progressively reduced preference for alcohol as expressed in a free choice beverage procedure, whereas 400 mg/kg/day of Acamprosate immediately stopped this behaviour. Acamprosate (50 mg/kg/day) also reduced the spontaneous activity of rats during the withdrawal syndrome. By contrast, Diazepam (5 mg/kg) induced inversion in the animals' choice (i.e. increased water consumption versus decreased alcohol intake) during the same experimental procedure, and potentiated the alcohol-induced hypermotility of the animals during the withdrawal syndrome without altering cortical hypervascularization. Taken together, our data provide evidence that both substances exert dose-dependent effects on preference towards alcohol, but display opposite profiles on spontaneous motor activity during the withdrawal phase without any modification of brain microvascularization or blood alcohol levels.

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Cholecystokinin octapeptide (CCK8) coexists with dopamine (DA) in a subpopulation of mesolimbic DA neurons including the projections to the nucleus accumbens. In this structure, CCK8 has been reported to exert agonist-like or antagonist-like effects on DA-mediated behaviours and on amphetamine's locomotor-activating effects in rodents. These findings raise the possibility that CCK8 plays a role in modulating the neurochemical mechanisms underlying the effects of DA and amphetamine in the mesolimbic DA system. The purpose of this study was to determine regional tissue monoamine levels in the rat brain and their modulation following injection of CCK8 in the nucleus accumbens. The same paradigm was used to determine the effects of this octapeptide on changes in amine levels induced by amphetamine administered intraperitoneally. DA, norepinephrine (NE), serotonin (5-HT) and their primary metabolites, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured using a reversed-phase ion pair high-pressure liquid chromatography system with electrochemical detection (HPLC-ED). Frontal cortex displayed the highest DOPAC/DA ratio and the lowest DOPAC/HVA ratio in contrast to the olfactory tubercle. The intraperitoneal injection of amphetamine (1 mg/Kg) followed by the intra-accumbens administration of 0.15M saline decreased the levels of DOPAC and increased DA, 5-HT and 5-HIAA both in nucleus caudatus and nucleus accumbens. The DA agonist induced a decrease in the level of NE in olfactory tubercle and frontal cortex. The direct administration of CCK8 (300 pmol) into the nucleus accumbens decreased the level of DA, DOPAC and 5-HT mainly in olfactory tubercle and nucleus accumbens itself.(ABSTRACT TRUNCATED AT 250 WORDS)

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