Specific changes in local cerebral glucose utilization in the rat brain induced by acute and chronic diazepam

Abstract

The effect of acute and long term administration of diazepam upon local cerebral glucose utilization (LCGU) in discrete regions of the central nervous system of the rat was studied by means of a quantitative autoradiographic [14C]2-deoxy-D-glucose technique. A single injection of diazepam (1.0 mg/kg and 2.5 mg/kg i.v.) reduced LCGU up to 30% in particular brain areas, such as the lateral and ventral thalamic nuclei, the medial geniculate body and the mamillary body, whereas the activity in many other structures was not significantly altered. That the effects may be mediated via specific benzodiazepine receptors was indicated by the ability of the selective benzodiazepine antagonist Ro 15-1788 (imidazobenzodiazepine) to attenuate these actions. Rats treated chronically with diazepam (20 mg/kg day for a period of 14 days) still displayed slight reductions of LCGU in certain areas affected acutely such as the lateral thalamic nucleus. In contrast to its effects in rats chronically treated with vehicle, an acute diazepam injection failed to significantly modify LCGU in rats chronically treated with diazepam. Furthermore, in chronic diazepam-treated animals Ro 15-1788 produced an increase of LCGU to values above control levels in those brain regions in which a decrement was seen upon acute diazepam administration to naive rats. These findings indicate an adaptation to and a possible development of physical dependence upon chronic drug treatment.