Influence of Environment on the Efficacy of Intrastriatal Dopaminergic Grafts

Abstract

Functional recovery is influenced by experience. The aim of the present work was to examine the effects of “enriched” environment (EE) versus an “impoverished” environment on the anatomical and functional integration of intrastriatal dopaminergic grafts. These influences were studied using a paradigm where grafting was performed before the dopamine-depleting lesion. Dopaminergic grafts were implanted into the left neostriatum of adult male rats. In the enriched group, grafted rats were housed collectively and were trained on different behavioral tests following grafting. In contrast, impoverished grafted rats were housed individually and not further manipulated. Ten weeks after grafting, the mesotelencephalic dopaminergic pathway was destroyed unilaterally to the grafted side and different behaviors were followed for 7 months. Grafting prior to lesioning had no prophylactic effects on the performance as the graft did not prevent the onset of the lesion-induced impairments. However, under EE conditions, a graft effect was manifested in the reduction of drug-induced rotation and on the indices of bias as tested by a spatial alternation test. No positive graft effects were observed in the skilled paw reaching test. Grafted rats raised under impoverished conditions performed in a fashion indistinguishable from the control lesioned animals on most measures of behavior. A beneficial effect of EE conditions was observed on survival of TH-positive neurons within the grafts. The results suggest that survival of grafted neurons, and the reduction of the magnitude of particular behavioral impairments, can be optimized by increasing the complexity of the subject's environment.