Bidirectional effects of GABAergic agonists and antagonists on maintenance of voluntary ethanol intake in rats

Abstract

The effects of THIP (GABAA agonist) and picrotoxin (GABA antagonist) on the maintenance of voluntary ethanol ingestion were examined. Thirty-three male Long-Evans rats were initially exposed to a screening procedure in which increasing concentrations of ethanol (from 2% to 9%) were presented in a free choice with water, on an alternate day schedule. Following the screening procedure, the rats were exposed to five ethanol presentations at a concentration of 9%, which constituted the baseline period, and five additional ethanol presentations during which the effects of the GABAergic manipulations were determined (test period). During the test period, the animals received IP injections of either 16 mg/kg of THIP, 2 mg/kg of picrotoxin or saline. The results suggested that the differential GABA manipulations resulted in bidirectional effects on the consumption of ethanol. More specifically, the GABAA agonist THIP increased the intake of ethanol as compared to baseline measures, while the GABA antagonist picrotoxin decreased ethanol intake. Similarly, the administration of THIP increased ethanol preference. In contrast, preference for ethanol over water was decreased following the administration of picrotoxin. It appears that the effects of these GABAergic manipulations are specific to ethanol, since total fluid intake was not influenced by the administration of either drug (i.e., THIP or picrotoxin). In light of the literature suggesting that THIP and picrotoxin are active at different sites within the GABAA chloride-ionophore receptor complex, the present findings would suggest that the GABAA receptor may play a role in regulating the voluntary intake of ethanol.