Subthalamic nucleus lesions induce deficits as well as benefits in the hemiparkinsonian rat

Lesions of the subthalamic nucleus can restore some imbalances in motor out put of the basal ganglia induced by nigrostriatal dopamine depletion, and h ave been proposed as a potential therapy for Parkinson's disease. Although there is substantial supporting evidence from experimental studies in both rats and primates, there is less information on the effects of subthalamic lesions alone. In order to characterize potential side effects, the present study evaluates the behavioural effects of unilateral excitotoxic lesions of the subthalamic nucleus in rats that have previously received either uni lateral saline or 6-hydroxydopamine injections into the nigrostriatal bundl e on the same side. The 6-hydroxydopamine lesions induced ipsilateral orien tation asymmetries in head position and body axis bias, rotational asymmetr ies following injections of direct or indirect dopamine agonists, neglect o f contralateral stimuli, and a reduction in the numbers of pellets retrieve d with the contralateral paw in a skilled reaching task. Subsequent excitot oxic lesions of the subthalamic nucleus reduced (but did not abolish) rotat ional asymmetries, had no effects on the measures of neglect and skilled pa w-reaching, and produced contralateral orientation biases in head turning a nd body axis curling. Rats that received subthalamic lesions alone exhibite d de novo impairments comprising contralateral biases in the orientation te sts. These results support a neuromodulatory role of the subthalamic nucleu s in regulating motor outputs of the basal ganglia, and caution that there may be distinct side effects of the lesion by itself. Whereas some impairme nts attributable to dopamine depletion may be alleviated by subthalamic man ipulations, other symptoms are not, or may even be aggravated.