Transplantation of embryonic mesencephalic and medullary raphe neurons to the neostriatum of rats with unilateral 6-hydroxydopamine lesions

The implantation of dopamine-rich mesencephalic grafts into the 6-hydroxydopamine (6-OHDA)-lesioned neostriatum of rats was accompanied by marked hyperinnervation by serotonin (5-HT) fibers. The purpose of this study was to examine the possibility that the graft-derived 5-HT hyperinnervation is governed by target-related effects present in the host neostriatum and the question of whether grafts rich in 5-HT cells can ameliorate the drug-induced motor asymmetry resulting from unilateral 6-OHDA lesions. Rats were allocated to one of two groups: lesion plus mesencephalic raphe grafts (group R5-HT/L); and lesion plus medullary raphe grafts (group C5-HT/L). A third group, sham-lesion plus mesencephalic raphe grafts (group R5-HT/S) was included. Complete recovery of (+)-amphetamine-induced rotation was observed only in rats which received 5-HT grafts derived from medullary raphe neurons. There was no marked recovery of apomorphine-induced rotation in either of the R5-HT/L and C5-HT/L groups. Immunohistochemistry showed that the R5-HT/L and C5-HT/L groups had 5-HT hyperinnervation in the neostriatum of the lesioned side. There was no target-related effect of the 6-OHDA-lesioned neostriatum specific for the different types of 5-HT tissue. It seems likely that the 5-HT tissue derived from the medullary raphe may contain additional neurotransmitters which contribute to the behavioral recovery.