Hyper-reactivity to amphetamine in rats with dopaminergic grafts

Rats with dopaminergic lesions were subsequently given grafts of dopaminergic (DA) neurons in various brain regions, and later tested for behavioral reactivity to amphetamine. Two experimental situations were used. Amphetamine-induced circling behavior was measured in animals with unilateral lesion of the nigrostriatal pathway implanted with intrastriatal grafts, locomotor activation by amphetamine was measured in animals with bilateral lesions and grafts in the nucleus accumbens. In both situations, behavioral overcompensation was observed after grafting. Ipsilateral circling, which is caracteristic of a unilateral lesion of the nigrostriatal pathway, gave way to contralateral circling, and locomotor activity was restored to levels above those observed for control animals. This behavioral overcompensation is a reflection of hyper-reactivity of grafted animals to amphetamine: they were found to respond to much lower doses than controls and the effect of the drug lasted longer. This enhanced response does not seem to be due to postsynaptic hypersensitivity, but rather to hyper-reactivity of the grafted neurons themselves to amphetamine. The mechanism of this phenomenon, which seems to be a general property of grafted DA neurons is discussed.