Abstract
GABA (4-aminobutyric acid) and its bicyclic analog THIP (4,5,6,7-tetrahydroisoxazolo-[4,5-c]-pyridin-3-ol) produced membrane hyperpolarization and increased chloride ion conductance of mouse spinal cord neurons in cell culture. Above 1 nM diazepam enhanced the actions of both GABA and THIP with similar potency and efficacy. Diazepam has been shown to enhance the binding of [ 3H]GABA to rat brain membranes over similar concentration ranges, with the EC 50 values for enhancement of [ 3H]GABA binding and increase in membrane conductance being similar. In contrast, binding of [ 3H]THIP has been shown to be unaltered by diazepam under a variety of conditions. The possible reasons for such a discrepancy between these electrophysiological and neurochemical results with THIP are discussed.
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