Delta enkephalin analogue [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been sh
own to protect dopamine transporters from methamphetamine-induced neurotoxi
city. In the present study, we demonstrate that exposure of embryonic ventr
al mesencephalic cells to DADLE (0.01 g/ml). prior to intrastriatal transpl
antation. enhanced functional recovery and graft survival in 6-hydroxydopam
ine-induced hemiparkinsonian rats. At 6 and 8 weeks posttransplantation, an
imals that received DADLE-treated cell grafts exhibited significantly highe
r (near normal) spontaneous locomotor behaviors, as well as trends of great
er reversal of motor asymmetrical behaviors compared with animals that rece
ived nontreated cell grafts. Histological examination revealed that animals
transplanted with DADLE-treated cell grafts exhibited about twice the numb
er of surviving tyrosine hydroxylase-immunoreactive grafted neurons compare
d with those animals that received nontreated cell grafts. These results su
ggest that DADLE should be considered as an adjunctive agent for neural tra
nsplantation therapy in Parkinson's disease.