Embryonic striatal grafts reverse the disinhibitory effects of ibotenic acid lesions of the ventral striatum.

Abstract

Bilateral damage to the ventral striatum induced by the excitotoxin ibotenic acid was found to have profound disinhibitory effects on rats' behaviour. Lesioned animals were unable to acquire efficient levels of performance on an operant schedule (differential reinforcement of low rates of responding, DRL) that required them to inhibit a previously rewarded response. In addition, lesioned subjects were relatively resistant to the disruptive effects of amphetamine on performance of the DRL schedule and were slower to cease responding under conditions of non-reward. A measure of unconditioned behaviour, overnight locomotor activity, was also disinhibited by the presence of the lesion. Grafts of embryonic striatal tissue transplanted to the lesioned ventral striatum were found to survive well. Moreover, the presence of the grafts reversed the effects of the lesion on measures of conditioned and unconditioned behaviour. The nature of the lesion-induced behavioural deficit and the ability of the embryonic transplants to reverse it are discussed in terms of the possible restoration of limbi-subcortical circuitry.