Behavioral effects of fetal substantia nigra tissue grafted into the dopamine-denervated striatum: responses to selective D1 and D2 dopamine receptor agonists

Abstract

Grafts of fetal ventral mesencephalon/substantia nigra cell suspensions into the dopamine-denervated striatum have been shown to reduce many of the behavioral alterations associated with striatal dopamine depletion. In this report, the behavioral response to amphetamine, apomorphine, the D1 receptor agonist SKF82958, and the D2 receptor agonist LY171555 were tested before and after intrastriatal grafts of fetal substantia nigra, of fetal striatum or no implantation procedure in animals with unilateral dopamine denervation. Grafts of fetal substantia nigra tissue were associated with significant behavioral recovery, as indicated by decreased turning induced by amphetamine (P ≤ 0.005), SKF82958 (P < 0.005), and LY171555 (P < 0.002). These effects were significantly different from the response in animals that did not receive grafts (P < 0.05) and occurred in the absence of decreased apomorphine-induced turning. These data suggest that the response to selective D1 or D2 dopamine receptor agonists is diminished following grafts of fetal dopaminergic tissue and that this behavioral effect is dissociable from the phenomena of behavioral supersensitivity to apomorphine. In a subset of substantia nigra grafted animals, it was found that D1 or D2 dopamine receptor antagonists administered 30 min prior to apomorphine could significantly reduce apomorphine-induced turning.