Effects of substantia nigra lesions on forebrain 2-deoxyglucose retention in the rat

A method was developed for the measurement of regional 2-deoxyglucose (2-DG) retention in rat brain by injecting tracer quantities of tritated 2-DG intravenously, dissecting out individual brain regions, making extracts of the tissue, and counting aliquots of the extracts. This technique permits the separation of unreacted 2-DG from 2-deoxyglucose-6-phosphate (2-DGP) by ion exchange chromatography as well as the performance of other biochemical measurements on the extracts. Using this method, the effect of unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra on 2-DG retention and 2-DGP formation by the striatum and the cerebral cortex was investigated. Animals were studied both 3 days and 2--4 weeks after lesioning. The location and efficacy of the lesions were verified histologically, behaviorally (by observing rotational behavior), and biochemically (by assay of striatal dopamine concentration or tyrosine hydroxylase activity). The lesions induced a mean asymmetry of less than 10% in 2-DG retention and in 2-DGP formation in striatum and cerebral cortex. This result was verified by [14C]2-DG autoradiography. Systemic administration of amphetamine (5 mg/kg) or apomorphine HBr (1.5 mg/kg) elicited rotational behavior, but did not induce a marked asymmetry of 2-DG retention in the regions studied. It is concluded that unilateral lesions of the nigrostriatal dopaminergic pathway have, at most, a modest effect on 2-DG retention by forebrain structures. We also conclude that vehicle injections may produce morphological and chemical evidence of brain injury, including small but reproducible changes in deoxyglucose retention.