Effect of fetal nigra transplantation on extracellular concentration of 5-hydroxytryptophan in the dopamine-depleted striatum of rats

In vivo microdialysis was used to examine the effects of dopaminergic transplants on extracellular 5-hydroxytryptophan (5-HTP) accumulation as an index of in vivo activity of tryptophan hydroxylase (TRH) in denervated rat striatum. Fetal substantia nigra (SN) transplants recovered the reduction of striatal dopamine (DA) in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal pathway. The transplants also recovered the reduction (whereas the reduction was not significant statistically) of serotonin in the denervated striatum. Dialysis perfusates were collected from intact, 6-OHDA lesion plus sham grafted and lesion plus SN grafted striata. The rat striatum was perfused with NSD-1015, an inhibitor of aromatic L-amino acid decarboxylase, and 1-3,4-dihydroxyphenylalanine (1-DOPA) and 5-HTP accumulation in dialysate were measured simultaneously. In response to NSD-1015, 5-HTP was substantially elevated in SN grafted striata in comparison with in sham grafted striata. These results provide evidence that implantation of DA-rich SN grafts into the 6-OHDA-lesioned striatum of rats is accompanied by hyperactivity of TRH which may attenuate the undesirable effects of 1-DOPA therapy in parkinsonism.