THE DETRIMENTAL EFFECT OF LEVODOPA ON BEHAVIORAL EFFICACY OF FETAL DOPAMINE NEURON GRAFTS IN RATS IS REVERSIBLE FOLLOWING PROLONGED WITHDRAWAL OF CHRONIC DOSING

In previous studies, we observed that chronic levodopa treatment resul ted in impaired morphology and function of grafted dopamine neurons in rats. To begin to better understand how levodopa treatment might infl uence dopamine neurons, we examined whether subsequent discontinuation of chronic levodopa treatment might allow for recovery of graft effic acy. Function of embryonic mesencephalic tissue grafts was assessed by monitoring rotational behavior elicited by amphetamine in lesioned, g rafted rats initially treated for 6 weeks with levodopa followed by a 6 week drug-free period. As observed previously, control grafted anima ls, but not levodopa treated animals, showed behavioral improvement. H owever, following a 6 week withdrawal period, the levodopa animals dem onstrated a significant reduction in amphetamine rotations which was r eminiscent of control animals. This suggests that grafted neurons can recover functionally after levodopa treatment is withdrawn, which may be of significance in clinical transplantation trials.