Abstract

In a model of Parkinson's disease (PD), amphetamine, a dopamine (DA)-releasing drug, fails to induce ipsilateral drug rotations in a proportion of rats with complete unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle and DA neurons of the substantia nigra. To investigate this phenomenon, individual 6-OHDA lesions (measured by tyrosine hydroxylase immunohistochemistry) in the substantia nigra pars compacta (A9), ventral tegmental area (A10), and striatum were examined in conjunction with outcomes of four behavioral tests. The behavioral tests were skilled paw reaching, a head-turning test, and apomorphine (0.05 mg/kg) and amphetamine (4 mg/kg) drug-induced rotations. Four weeks postlesion, ipsilateral side bias measured by the head-turning test correlated strongly with extent of A9 DA neuronal lesion. Additional A10 neuronal DA lesions did not substantially improve the model fit, indicating that the head-turning bias was primarily A9 dependent. In contrast, total head-turning activity increased monotonically with lesions of A10 striatal DA fibers. Skilled paw-reaching accuracy decreased with increased lesion of both A9 and A10 DA neuronal systems. Associating amphetamine-induced rotations with extent of A9 DA lesion generated a second-order polynomial model, y = -11.1x + 0.20 x(2) + 208.7 (R(2) = 0.73), with an overall F ratio (df = 2,21) of 28.4 (P