The role of the alpha 1 and alpha 2 containing GABA(A) receptors in mediating the neurobehavioral properties of ethanol (EtOH)
Abstract
In the present study, a series of experiments were conducted to investigate the role of the α1 containing GABAA receptor in the neurobehavioral effects of EtOH. In experiment 1, the relationship between the expression of mRNA for the α1 and α2 containing GABAA receptors in the extended amygdala and innate EtOH preference was examined. In experiment 2, the effects of complete deletion of the GABAA α1 subunit receptor on EtOH (10% v/v) and sucrose (10% w/v) motivated responding were examined. In experiment 3, the GABAA α1 knockout (α1 (−/−) KO) and the wild-type control (α1 (+/+) WT) mice were given access to EtOH (10% v/v) in the 2.0 hour limited access forced choice paradigm. In experiment 4, the effects of EtOH on locomotor activity were tested in the α1 (−/−) KO and control mice. Finally, in order to attenuate the EtOH-induced effects on locomotor activity, βCCt, the selective α1 mixed agonist-antagonist and flumazenil, the non-selective benzodiazepine antagonist, were co-administered with EtOH. The HAD-1 rats had a higher distribution of the α2 containing GABAA receptor in the bed nucleus of the stria terminalis (BNST). In experiment 2, the α1 (−/−) KO mice lever-pressed for significantly less EtOH (10% v/v) and sucrose (10% w/v) in comparison to the α1 (+/+) WT mice. Similarly, the α1 (−/−) KO mice consumed significantly less EtOH (10% v/v) in the 2.0 hour limited access forced choice paradigm. The results from experiment 4 demonstrated the α1 (−/−) KO mice were less sensitive to the se dative effects of EtOH and more sensitive to the stimulant effects of EtOH. Finally, βCCt, but not flumazenil, was able to attenuate the EtOH-induced effects in the α1 (−/−) KO mice. The results from this series of experiments suggest that the α 1 and α2 containing GABAA receptors play a salient role in the neurobehavioral effects of EtOH.
Degree
Ph.D.
Advisors
June, Purdue University.
Subject Area
Psychobiology|Neurology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.