Effects of nitrendipine, chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal.

1. Male hooded Lister rats were fed a liquid diet containing 10% absolute ethanol for 4-5 weeks. Control rats received the liquid diet in amounts controlled to produce equal weight gain. 2. The rats were tested 7.5 h after withdrawal of ethanol and 30 min after i.p. injection with nitrendipine, chlordiazepoxide or baclofen or 20 min after i.p. injection with flumazenil. 3. Nitrendipine (25-100 mg/kg) was unable to reverse the anxiogenic responses detected on withdrawal from ethanol, but the highest dose did reduce withdrawal tremor. 4. Chlordiazepoxide (10 mg/kg), flumazenil (4 mg/kg) and baclofen (1.25 mg/kg) significantly reversed the anxiogenic response detected on withdrawal from ethanol. 5. These reversals of ethanol withdrawal responses are similar to the reversal of the increased anxiety detected on withdrawal from chronic treatment with benzodiazepines. 6. The mechanisms and clinical implications of these drug-induced reversals are discussed.