Cocaine-induced turning behavior in rats with 6-hydroxydopamine lesions: effect of transplants of fetal substantia nigra.

Rats with a unilateral 6-hydroxydopamine lesion of the dopaminergic nigrostriatal pathway were examined for cocaine-induced rotational behavior 1 month after receiving transplants of fetal substantia nigra grafted over the dopamine (DA)-deafferented striatum. The ipsiversive rotational behavior induced by cocaine was significantly reduced as compared with the pre-transplantation baseline, and occurred only during the first 2 min after injection. In all rats with transplants, cocaine induced strong contraversive rotation starting after 2-3 min and lasting for 10-15 min. This contraversive rotation, which was never observed in response to cocaine in rats prior to transplantation or in rats with sham transplants, was reproduced using nomifensine and GBR 12909, but not imipramine and fluoxetine. These results indicate that the transplant-reinnervated striatum responds selectively and in an exaggerated fashion to the actions of DA uptake inhibitors.