Effects of the GABA receptor agonist, progabide, upon local cerebral glucose utilization.

The effects of a specific GABA receptor agonist, progabide, have been examined on local cerebral glucose utilization through the use of the autoradiographic [14C]2-deoxyglucose technique in conscious rats. The intraperitoneal administration of progabide (80-320 mg.kg-1) resulted in a heterogeneous pattern of significantly reduced glucose utilization throughout the 50 discrete regions of the brain that were studied. Insignificant decreases in local cerebral glucose use were noted following the low dose of progabide (80 mg.kg-1). Following progabide (160 mg.kg-1), reductions of approximately 20% in glucose utilization were observed in most of the extrapyramidal system (substantia nigra, pars compacta and reticulata; globus pallidus; caudate nucleus), some thalamic nuclei (lateral geniculate body, anterior and ventrolateral thalamic nuclei), a number of areas related to the limbic system (cingulate cortex; amygdala; hypothalamus; lateral habenula; nucleus accumbens; dorsal hippocampus as well as the CA3 field) and the raphé nuclei. In contrast, layer IV of the neocortex, the cerebellum and cerebellar nuclei, displayed only minimal (10-15%) reductions in glucose utilization. At the highest dose (320 mg.kg-1) examined, progabide effected widespread though heterogeneously distributed decreases in glucose use. The overall pattern of decreased glucose use seen with progabide was different from that noted with previously studied GABA-mimetic drugs, such as muscimol, except for those changes observed in the extrapyramidal and sensory-motor areas for which similar dose-response relationships occurred. A significant correlation was observed between progabide-induced decreases in glucose utilization and in serotonin synthesis in a number of brain areas. The pattern of progabide-induced changes in integrated functional activity is compatible with its neurochemical spectrum and could indicate the loci at which its anticonvulsant, antidepressant and extrapyramidal activities are initiated.