Time-course and regional distribution of the metabolic effects of bromocriptine in the rat brain

Local cerebral glucose utilization (LCGU) and motor behavior were examined in awake Fischer-344 rats after administration of the dopaminergic agonist bromocriptine (BROMO). LCGU was measured using the [14C]2-deoxyglucose technique in 63 brain regions at 1,2,3 or 4 h after BROMO 20 mg/kg, and at 4 h after BROMO 100 mg/kg i.p. At 2 h, LCGU was reduced significantly in 13% of the 63 regions examined. The affected regions are related to the topographical distribution of dopaminergic innervation in the brain. At 3-4 h, LCGU remained depressed in some of the above dopaminergic regions, but was elevated significantly in regions which are involved in sensorimotor function. BROMO also produced two behavioral effects depending on time after administration. Locomotor activity was depressed at 1-2 h, and stereotyped behavior appeared at 3-4 h. The time-dependent effects of BROMO may reflect progressively increasing brain concentrations of the drug or of its active metabolites. The coincidence of locomotor depression and reduction of LCGU in dopaminergic regions suggests a role of dopamine autoreceptors in regulation of motor function. Metabolic stimulation of many non-dopaminergic regions when stereotypy is evident suggests that circuit(s) involving these areas may contribute to stereotypy.