Pharmacological evaluation of alcohol withdrawal-induced inhibition of exploratory behaviour and supersensitivity to harmine-induced tremor.
Rats given a liquid diet containing 10% (v/v) alcohol consume high quantities of alcohol. Within 8 hr after cessation of the alcohol intake, the animals will show alcohol-withdrawal reactions including a supersensitivity to harmine-induced tremor and an inhibition of exploratory behaviour in a neutral environment. Several drugs can overcome one or more of these alcohol-withdrawal reactions. A reduction of the alcohol withdrawal-induced inhibition of exploration, in terms of both the number of transits into the open field and the time spent in the open field, was obtained with chlordiazepoxide, ritanserin, mianserin and propranolol. Of these four compounds, propranolol and mianserin were also active against the supersensitivity to both 5.00 and 10.00 mg/kg harmine-induced tremor. Chlordiazepoxide and ritanserin were only active against 5.00 mg/kg harmine. Other compounds that reversed the supersensitivity to harmine-induced tremor during alcohol withdrawal included buspirone, fluoxetine, haloperidol, clonidine, flunarizine and baclofen. Very limited effects on both alcohol-withdrawal reactions were observed with ondansetron, nimodipine and MK-801. Risperidone and SCH 23390 were inactive. These results demonstrate that some alcohol withdrawal reactions can be studied in a systematic way and that various pharmacological agents can differentially interact with these alcohol withdrawal reactions.
Meert
T F
TF
Department of Neuropsychopharmacology, Janssen Research Foundation, Beerse, Belgium.
D000430:Alcohol Withdrawal Delirium / Q000503:physiopathology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D000431:Ethanol / Q000493:pharmacokinetics; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D006247:Harmine / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D014202:Tremor / Q000139:chemically induced / Q000503:physiopathology*
D018377:Neurotransmitter Agents; D011619:Psychotropic Drugs; D017981:Receptors, Neurotransmitter; D000431:Ethanol; D006247:Harmine