Uncoupling of cerebral blood flow and glucose utilization by dihydroergocristine in the conscious rat.

Dose-dependent effects of the dihydrogenated ergot alkaloid dihydroergocristine on physiological variables, local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were evaluated in the conscious rat after intravenous injection. Heart rate was reduced with 2.5 mg/kg and 20 mg/kg dihydroergocristine. LCBF and LCGU were determined autoradiographically by employing the 14C-iodoantipyrine or 14C-2-deoxyglucose technique, respectively. At a dose of 0.5 mg/kg, dihydroergocristine neither changed LCGU nor LCBF, while at 2.5 mg/kg a slight decrease in LCGU was measured, which was more pronounced at 20 mg/kg. LCBF was significantly increased in several structures at 2.5 mg/kg, but it was markedly reduced at 20 mg/kg. The divergent effects on LCBF and LCGU at a dose of 2.5 mg/kg suggest a potential capacity of dihydroergocristine to uncouple the close interrelation of cerebral blood flow and cerebral energy metabolism.

Effects of the indirect dopaminomimetic diethylpemoline on local cerebral glucose utilization and local cerebral blood flow in the conscious rat.

The changes in local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) following the systemic application of the indirect dopaminomimetic diethylpemoline (50 mg/kg i.v.) were measured in conscious rats using the autoradiographic [14C]2-deoxyglucose and the [14C] iodoantipyrine technique. Increased rates of glucose utilization were observed in the sensorimotor cortex, parafascicular nucleus, ventrolateral nucleus of the thalamus, substantia nigra, caudate nucleus, globus pallidus, red nucleus, subthalamic nucleus, cerebellar cortex and vermis. Cingulate cortex, anteromedial, anteroventral nucleus of the thalamus, habenula and nucleus accumbens showed a decreased LCGU. The determination of LCBF revealed a similar pattern of altered blood flow values. Statistical evaluation of the relationship between glucose utilization and blood flow by regression analysis did not reveal any distinguishable difference between diethylpemoline-treated rats and controls. The data suggest that it is mainly the altered neuronal activity and metabolic demand after dopaminergic stimulation that effect the changes in blood flow rather than a direct dopaminergic effect on brain vasculature.