Diazepam potentiates GABA-, but not adenosine-mediated, inhibition of neurons of the nigral pars reticulata

Abstract

Experiments were conducted to assess the relative roles of gamma-aminobutyric acid (GABA) and adenosine in mediating the inhibition of neuronal activity by diazepam injected intravenously. Recent studies have shown that benzodiazepines inhibit, in a dose-dependent manner, the firing of neurons in the substantia nigra pars reticulata. In support of a predominantly GABAergic mechanism for this inhibitory action, a small dose of diazepam (50 micrograms/kg, i.v.), which itself had little effect on cell firing, significantly potentiated the inhibitory responses of neurons of the pars reticulata to muscimol, a potent GABA agonist given intravenously, and significantly and selectively potentiated the inhibition of reticulata neurons by GABA applied iontophoretically. In contrast to their extreme sensitivity to GABAergic inhibition, neurons of the pars reticulata were comparatively insensitive to systemically and iontophoretically administered adenosine-related drugs. However, in those instances when inhibitions could be achieved with iontophoretically applied adenosine-5'-monophosphate, the inhibitory responses were not significantly modified by a 50 micrograms/kg (i.v.) dose of diazepam. These findings, considered in light of differences in GABA and adenosine receptor densities within the substantia nigra, suggest that the benzodiazepine-induced inhibition of neurons of the nigral pars reticulata most likely involves potentiation of GABA but not adenosine-mediated influences.