The lateral vestibular nucleus is a site for the depressant action of benzodiazepines on the crossed extensor reflex

Abstract

The effects of diazepam microinjected into the subcerebellar nuclei, the lateral vestibular nucleus (LVN), the red nucleus and the substantia nigra were investigated using the crossed extensor reflex (CER) model in chloralose-anesthetized rats. Microinjections of diazepam at doses of 1 and 25 ng/animal into the left LVN, ipsilateral to the testing muscle, produced a dose-related CER depression, while injections of diazepam at a dose of up to 100 ng/animal into the right LVN and into other regions tested produced little effect. The CER depression produced by diazepam could be clearly reversed by a subsequent intravenous administration of Ro 15-1788, a benzodiazepine antagonist. Electrical lesions of the left LVN decreased the amplitude of CER in otherwise untreated rats. Intravenously administered diazepam at a dose of 0.01 or 0.05 mg/kg decreased spontaneous firing of LVN neurons. Iontophoretically applied GABA or flurazepam, a water-soluble benzodiazepine, decreased the spontaneous firing of LVN neurons. Depressant actions on neuronal activity in the LVN produced by both diazepam and flurazepam were clearly antagonized by intravenously administered Ro 15-1788, while it failed to reverse the depression produced by GABA. These findings indicate that the LVN is a major site of the CER depressant action of benzodiazepines and a possible mechanism of action is discussed.