Effects of chronic diazepam exposure on GABA sensitivity and on benzodiazepine potentiation of GABA-mediated responses of substantia nigra pars reticulata neurons of rats.

This study examined the effects of chronic diazepam treatment on GABA sensitivity of substantia nigra pars reticulata neurons and on the ability of benzodiazepines to enhance GABAergic responses of these neurons in rats. Chronic diazepam exposure failed to significantly alter the sensitivity of reticulata neurons to microiontophoretically applied GABA. However, following chronic diazepam treatment for 1 day, or 1, 3 or 7-11 weeks, reticulata neurons showed tolerance to additional systemically or iontophoretically applied benzodiazepines and displayed an increased firing rate following injection of Ro 15-1788. These changes were not apparent 24 h after cessation of chronic treatment. Thus, tolerance to the effects of benzodiazepines on reticulata neurons appeared to develop after a single day of diazepam exposure and to dissipate by 24 h after cessation of treatment. When compared to our previous studies on dorsal raphe neurons, these results demonstrate regional differences in neuronal responses to chronic diazepam exposure, which may help elucidate neural systems which are involved in tolerance to the various functional aspects of benzodiazepines.