Date of Defense

Fall 12-15-1994


Biological Sciences

First Advisor

Leonard C. Ginsberg

Second Advisor

Montford F. Piercey, Upjohn Company


The effects of U-95666A, a highly selective dopaminergic D2 receptor agonist, on local cerebral glucose utilization (LCGU) were studied via the Sokoloff 2-deoxy-D-[14C]-glucose autoradiography technique in lesioned (Parkinson's model) and non-lesioned rats. The idea behind this method is that neuronal activity is directly related to glucose metabolism in the brain. Five treatment groups were studied: control, U-95666A, u-95666A + haloperidol, lesion control, and lesion U-95666A. The lesions were induced using unilateral injections of 6-hydroxydopamine into the substantia nigra, thus destroying the dopamine neurons there and creating a hemiparkinsonian state of Parkinson's disease in the rats. Administration of this compound to the non-lesioned rats resulted in an overall depression of metabolism. LCGU in 35 of 65 analyzed areas showed statistically significant depression with U-95666A. LCGU in 118 of 121 analyzed regions was significantly depressed with U-95666A + haloperidol as compared to control. LCGU was depressed in 7 areas with the drug and haloperidol as compared to the drug alone. U-95666A in the lesioned animals did not seem to have much activity. Administration of the drug to lesioned animals produced a sinificant change (either LCGU depression or stimulation) in only 5 areas. With left and right hemispheric comparisons in selected areas, only one change (depression) of LCGU was noted.

Access Setting

Honors Thesis-Campus Only