Depression of benzodiazepine binding and diazepam potentiation of GABA-mediated inhibition after chronic exposure of spinal cord cultures to diazepam

Abstract

Cultures of fetal mouse spinal cord were exposed to 12.6 microM (3.6 micrograms/ml) diazepam for 7 days. After drug removal, benzodiazepine receptor binding was assayed on intact cells and intracellular recordings of diazepam effects on GABA-mediated inhibitory responses were obtained. The biochemical and electrophysiological data revealed significant and parallel reductions in both receptor binding and pharmacological action on GABA responses which did not return to control levels until 3-4 days after removal of diazepam. The results indicate that chronic exposure of spinal cord cultures to diazepam results in a reversible down-regulation of diazepam binding and function.