The effect of diazepam upon local cerebral glucose use in the conscious rat

Abstract

The effects of diazepam (0.1–1.0 mg/kg i.v.) upon local cerebral glucose utilization, were analysed in 61 anatomically discrete areas of the conscious rat brain using [ 14C]-2-deoxyglucose quantitative autoradiography. The administration of diazepam resulted in significant reductions in the rate of glucose use in every region investigated. The regional pattern of alterations in glucose utilization was rather homogeneous, with the majority of brain regions analysed showing reductions of between 20 and 40% in response to 0.3 mg/kg diazepam. Only two regions of the central nervous system differed significantly from the widespread, homogeneous reductions. In the mammillary body, the rate of glucose utilization was more sensitive to depression than elsewhere in the brain (55% reductions following 0.3 mg/kg diazepam), whilst in the lateral amygdala, the rate of glucose use was less sensitive (8% reductions following 0.3 mg/kg diazepam). The effects of diazepam were compared to those elicited by i.v. injection of the γ-aminobutyric acid (GABA) agonists, muscimol and tetrahydroisoxazolopyridinol (THIP), as reported previously by the authors. 12 Although muscimol and THIP, like diazepam, reduced glucose use in every region of the brain, visual inspection of the autoradiograms suggested that whilst the patterns of regional responsiveness to the two GABA agonists were almost identical, they were different to the pattern of response evoked by diazepam. A rigorous system of analysis was devised making use of the dose-response profiles in each of the 61 brain areas to construct a regional hierarchy of responsiveness to the three drugs and allowing comparison of their effects on the brain as a whole. This critical form of data evaluation revealed that there was a more regionally homogeneous response to diazepam than to either muscimol or THIP, and whilst the regional hierarchy of responses to the GABA agonists was very similar, both differed from diazepam. It would appear that whilst benzodiazepines may interact with the GABA receptor, their effects upon the integrated functional activity of the brain as a whole differs markedly from that evoked by putative GABA receptor agonists.