Psychopharmacology

, Volume 172, Issue 3, pp 255–263

GABAA1 receptor agonists and antagonists: effects on species-typical and heightened aggressive behavior after alcohol self-administration in mice

  • Rosa M. M. de Almeida
  • James K. Rowlett
  • James M. Cook
  • Wenyuan Yin
  • Klaus A. Miczek
Original Investigation

DOI: 10.1007/s00213-003-1661-1

Cite this article as:
de Almeida, R.M.M., Rowlett, J.K., Cook, J.M. et al. Psychopharmacology (2004) 172: 255. doi:10.1007/s00213-003-1661-1

Abstract

Rationale

The positive modulation of gamma-aminobutyric acid type-A (GABAA) receptors is a putative mechanism via which alcohol escalates aggressive behavior. Broad-spectrum benzodiazepine antagonists block alcohol-heightened aggression in rats and monkeys. However, the degree to which GABAA subunit composition plays a role in heightened aggressive behavior induced by self-administration of a moderate alcohol dose remains unresolved.

Objective

β-Carboline-3-carboxylate-t-butyl ester (β-CCt) and zolpidem act preferentially at GABAA receptors containing the α1 subunit as antagonist and agonist, respectively, and serve as useful tools to evaluate the role of GABAA receptor subtypes in self-administered alcohol on aggression.

Methods

Male resident mice, housed in breeding pairs, were conditioned to nose-poke in a removable panel in their home cage, with each fifth poke being reinforced by the delivery of 0.05 ml of 6% ethanol (EtOH). After consuming EtOH, the resident mice were given the antagonists β-CCt and flumazenil or agonists zolpidem and triazolam, and then confronted an intruder male in their home cage for a 5-min period.

Results

Following self-administration of EtOH (1.0 g/kg, 1.7 g/kg), 14 of 37 resident mice displayed unusually large increases in the frequency of attack bites and sideways threats. Flumazenil or β-CCt decreased alcohol-heightened and non-heightened aggression in a dose-dependent manner. Administration of 3 mg/kg β-CCt lowered the aggression-heightening effects of 1 g/kg and 1.7 g/kg EtOH, but did not antagonize the sedative effects of 3.0 g/kg EtOH. Triazolam and zolpidem decreased alcohol-heightened and non-heightened aggressive behavior, and these antiaggressive effects were accompanied by reduced motor activity, indicating sedation.

Conclusions

Benzodiazepine antagonists, particularly those acting preferentially at GABAA1 subunit-containing receptors, decrease alcohol-heightened and species-typical aggressive behavior, but are ineffective in attenuating the sedative effects of alcohol.

Keywords

GABA receptorsAggressionAlpha subunitsSelf-administrationBenzodiazepine receptorAlcoholHypnoticLocomotion

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Rosa M. M. de Almeida
    • 1
    • 2
  • James K. Rowlett
    • 4
  • James M. Cook
    • 5
  • Wenyuan Yin
    • 5
  • Klaus A. Miczek
    • 1
    • 3
  1. 1.Department of PsychologyTufts UniversityMedfordUSA
  2. 2.Centro de Ciências da SaúdeUnisinosSão LeopoldoBrazil
  3. 3.Department of Psychiatry, Pharmacology and NeuroscienceTufts UniversityBostonUSA
  4. 4.New England Regional Primate Research CenterHarvard Medical SchoolSouthboroughUSA
  5. 5.Department of ChemistryUniversity of Wisconsin-MilwaukeeMilwaukeeUSA