Acamprosate and diazepam differentially modulate alcohol-induced behavioural and cortical alterations in rats following chronic inhalation of ethanol vapour.
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.
Gewiss
M
M
Laboratoire de Psychobiologie, Université de Louvain, Belgium.
Heidbreder
C
C
Opsomer
L
L
Durbin
P
P
De Witte
P
P
D000077443:Acamprosate; D000280:Administration, Inhalation; D000428:Alcohol Drinking / Q000503:physiopathology*; D000435:Alcoholic Intoxication / Q000503:physiopathology; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D011963:Receptors, GABA-A; D013654:Taurine; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000077443:Acamprosate; D003975:Diazepam