Selective subregional dopamine depletions in the rat caudate-putamen following nigrostriatal lesions

Abstract

Previous work has demonstrated a complex neurochemical and neuroanatomical heterogeneity of the striatum in normal brains. The present research investigated whether the heterogeneous distribution of dopamine would be altered following unilateral injections of the neurotoxin 6-hydroxydopamine into the substantia nigra of the rat. Four weeks following injection, the nucleus accumbens and subregions of the caudate-putamen and substantia nigra were dissected and analyzed by HPLC with electrochemical detection for dopamine, 5-hydroxytryptamine, and their respective metabolites. Levels of dopamine and its metabolites in the anterodorsolateral caudate-putamen were depleted more than medial, posterior, and ventral, striatal areas in partially lesioned animals (less than 90% dopamine depletion). This resulted in an alteration of striatal heterogeneity such that a mediolateral gradient of dopamine tissue content was now superimposed on the normal rostrocaudal gradient observed in controls. Paralleling these findings, dopamine was more depleted in the lateral, as opposed to the medial, substantia nigra. These results indicate that the nigrostriatal dopamine system degenerates in a heterogeneous fashion following 6-hydroxydopamine administration. It is speculated that the differential loss of dopamine neurons observed in the nigra of Parkinson's patients may be due to a differential sensitivity to toxins within the nigra.