Effects of baclofen and nitrendipine on ethanol withdrawal responses in the rat.
Withdrawal of rats from 5 weeks of a liquid ethanol diet (10%), resulted in anxiogenic responses in the social interaction and elevated plus-maze tests of anxiety. The rats withdrawn from ethanol also showed increased aggression, tremor and rearing. Baclofen (1.25 and 2.5 mg/kg), but not nitrendipine (25-100 mg/kg), reversed the anxiogenic withdrawal responses, without having any effect in control animals and without having significant sedative effects. Baclofen reduced the enhanced aggression during withdrawal of ethanol, but this may have reflected a more general anti-aggressive action. Baclofen (2.5 mg/kg) reduced the withdrawal tremor. Nitrendipine (100 mg/kg) significantly reduced withdrawal tremor, but this dose was sedative, so this was likely to be a non-specific effect. It is proposed that the anxiogenic response during withdrawal of ethanol is due to a reduced GABA function, involving both GABAA and GABAB receptors.
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Psychopharmacology Research Unit, London University, Guy's Hospital, U.K.
Zharkovsky
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Gulati
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D000374:Aggression / Q000187:drug effects; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001418:Baclofen / Q000494:pharmacology*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D007398:Interpersonal Relations; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009568:Nitrendipine / Q000494:pharmacology*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control* / Q000523:psychology; D014202:Tremor / Q000503:physiopathology / Q000517:prevention & control
D000431:Ethanol; D009568:Nitrendipine; D001418:Baclofen