Abecarnil and alprazolam reverse anxiety-like behaviors induced by ethanol withdrawal

This study investigated the effects of a benzodiazepine partial agonist, abecamil, and a full agonist, alprazolam, on ethanol withdrawal-induced anxiety-like behaviors in rats. Anxiety was assessed in two models: elevated plus maze and pentylenetetrazol (GABAA antagonist) discrimination assay. Male rats received an ethanol-containing (4.5%) liquid diet for 7 to 10 days and were tested for withdrawal symptoms 12 h after termination of the diet. In the elevated plus maze, ethanol-withdrawn rats displayed less open arm activity and total arm entries than pair-fed rats. Abecarnil (0.08-0.32 mg/kg, IF) and alprazolam (0.08-1.25 mg/kg, IF) each produced a dose-dependent, full reversal of ethanol withdrawal-induced reduction of open arm activity, but only alprazolam increased the total arm entries. In the pentylenetetrazol assay, ethanol-withdrawn rats selected the pentylenetetrazol lever (100%) over the salin-lever. Abecarnil (0.04-0.32 mg/kg, IF) and alprazolam (0.08-0.32 mg/kg, IF) dose dependently reduced pentylenetetrazol-lever responding to control levels (10-20%). Alprazolam was more potent than abecamil in reversing ethanol withdrawal-induced decrease in open arm activities, but showed comparable potency and efficacy to abecamil in blocking the pentylenetetrazol-like ethanol withdrawal stimulus. These results suggest that abecamil and alprazolam may have therapeutic potential for treatment of ethanol withdrawal-induced anxiety-like symptoms. (C) 2000 Elsevier Science Inc. All rights reserved.