Abecarnil and alprazolam reverse anxiety-like behaviors induced by ethanol withdrawal.
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 In the elevated plus maze, ethanol-withdrawn rats displayed less open arm activity and total arm entries than pair-fed rats.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 In the pentylenetetrazol assay, ethanol-withdrawn rats selected the pentylenetetrazol lever (100%) over the salin-lever.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.
Jung
M E
ME
Department of Pharmacology, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA.mjung@hsc.unt.edu
Wallis
C J
CJ
Gatch
M B
MB
Lal
H
H
D000525:Alprazolam / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000008:administration & dosage / Q000627:therapeutic use*; D004193:Discrimination Learning; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D020318:Rats, Long-Evans; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000150:complications*
D014151:Anti-Anxiety Agents; D002243:Carbolines; D000431:Ethanol; C062769:abecarnil; D010433:Pentylenetetrazole; D000525:Alprazolam