Adrenal medulla grafts enhance functional activity of the striatal dopamine system following substantia nigra lesions

Abstract

Adrenal medulla grafts in the lateral ventricle reduce the behavioral manifestations of striatal dopamine depletion in an animal model of Parkinson's disease. Using microdialysis in freely moving rats, the present experiments determined that dopamine was not detectable in cerebrospinal fluid (CSF). However, adrenal medulla grafts were associated with an increase in dopamine turnover and amphetamine-stimulated striatal dopamine release was increased in animals with behaviorally effective adrenal medulla grafts. Therefore, adrenal medulla grafts increase striatal dopamine activity without an appreciable release of dopamine into the CSF. Adrenal medulla grafts also increased serum dopamine concentrations, and the increase in serum dopamine was directly correlated with the behavioral efficacy of the grafts. We suggest that dopamine, produced by adrenal medulla grafts, may gain access to the striatum via the blood supply and then leak out into the host striatum through permeable blood vessels adjacent to the graft. Through this mechanism, adrenal medulla grafts may increase functional dopaminergic activity in the striatum. These results may be important for understanding how autografts of adrenal medulla cells produce a putative alleviation of the symptoms of Parkinson's disease.