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

Marianna E. Jung, Cleatus J. Wallis, Michael B. Gatch, Harbans Lal

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

This study investigated the effects of a benzodiazepine partial agonist, abecarnil, 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 (GABA(A) 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 In the elevated plus maze, ethanol-withdrawn rats displayed less open arm activity and total arm entries than pair-fed rats.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, IP) and alprazolam (0.08-1.25 mg/kg, IP) 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 In the pentylenetetrazol assay, ethanol-withdrawn rats selected the pentylenetetrazol lever (100%) over the salin-lever.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, IP) and alprazolam (0.08-0.32 mg/kg, IP) dose dependently reduced pentylenetetrazol-lever responding to control levels (10-20%). Alprazolam was more potent than abecarnil in reversing ethanol withdrawal-induced decrease in open arm activities, but showed comparable potency and efficacy to abecarnil in blocking the pentylenetetrazol-like ethanol withdrawal stimulus. These results suggest that abecarnil and alprazolam may have therapeutic potential for treatment of ethanol withdrawal-induced anxiety-like symptoms.

Original languageEnglish
Pages (from-to)161-168
Number of pages8
JournalAlcohol
Volume21
Issue number2
DOIs
StatePublished - Jun 2000

Keywords

  • Abecarnil
  • Alprazolam
  • Anxiety
  • Elevated plus maze
  • Ethanol withdrawal
  • GABA receptor
  • Pentylenetetrazol discrimination

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