Effects of Acute Ethanol on GABA Release and GABA A Receptor Density in the Rat Mesolimbic System

Abstract

The present study has addressed whether acute ethanol administration mediates changes in GABA release and GABA A receptor density in the rat mesolimbic system. In vivo microdialysis was performed in the ventral pallidum and between the ventral tegmental area and substantia nigra of conscious ethanol-naive rats. Extracellular levels of endogenous GABA were stable in both brain regions and not significantly affected following administration of 5 ml of 20% ethanol by gavage, despite clear overt behavioral signs of intoxication. Two hours following ethanol administration, animals were decapitated and the brains processed for autoradiography. Adjacent tissue sections were incubated with [ 3H]SR95531 or [ 3H]muscimol and the resulting autoradiograms quantified. Binding of both radioligands was significantly reduced in the striatum of rats treated with ethanol compared to vehicle (15 ± 2% for [ 3H]SR95531 and 33 ± 6% for [ 3H]muscimol). In contrast, ethanol had no effect on [ 3H]SR95531 binding in hippocampus, while that of [ 3H]muscimol was increased by 100 ± 30%. Ethanol had no effect on the binding of either radioligand in all other areas examined. Therefore, while acute ethanol had no effect on the release of GABA in either the ventral pallidum or ventral tegmental area, changes in the binding density of GABA A ligands were observed in selected brain regions.