Behavioral changes associated with grafts of embryonic ventral mesencephalon tissue into the striatum and/or substantia nigra in a rat model of Parkinson’s Disease

Abstract

Unilateral 6-hydroxydopamine lesion of the ascending nigrostriatal pathway in rats is a commonly used model of Parkinson’s Disease. Transplantation of embryonic ventral mesencephalon (VM) into the striatum of such rats reduces drug-induced turning and ameliorates some simple behavioral deficits. While considerably less research has been conducted on the topic, VM grafts into the lesioned substantia nigra (SN) may induce recovery on more complex and/or spontaneous tasks. The present series of experiments was conducted to explicitly compare the behavioral efficacy of intrastriatal and intranigral VM grafts with the effects of grafts into both of these sites. Animals receiving control grafts were also tested. Following transplantation of VM or control tissue derived from E14 rat embryos, changes in drug-induced and spontaneous turning, as well as spontaneous paw use when rearing, were assessed each month for 5 months post-graft. Intrastriatal VM grafts were associated with decreases in drug-induced and spontaneous turning asymmetry but no change in paw use. Intranigral VM grafts did not affect drug-induced turning but decreased the asymmetry in spontaneous turning and spontaneous paw use. Following simultaneous VM grafts into the striatum and SN there was a decrease in drug-induced turning and an increase in the spontaneous use of the contralateral paw and both paws simultaneously. These results may have important implications for our understanding of the mechanisms mediating graft-induced behavioral recovery, both in the rat model of, and human Parkinson’s Disease.