SUBTHALAMIC NUCLEUS LESIONS - WIDESPREAD EFFECTS ON CHANGES IN GENE-EXPRESSION INDUCED BY NIGROSTRIATAL DOPAMINE DEPLETION IN RATS

Lesions of the subthalamic nucleus block behavioral effects of nigrost riatal dopamine depletion in rats and primates, but the contribution o f this region to the molecular effects of dopaminergic lesions is unkn own. The effects of subthalamic nucleus lesions alone or in combinatio n with a 6-hydroxydopamine-induced lesion of the substantia nigra were examined in adult rats. Unilateral subthalamic nucleus lesions caused ipsiversive rotation after peripheral administration of apomorphine a nd a small decrease in glutamic acid decarboxylase (GAD) mRNA in the i psilateral globus pallidus (external pallidum). Confirming previous re sults, nigrostriatal dopaminergic lesions caused contraversive rotatio n after apomorphine injection, and increased enkephalin mRNA in the st riatum, GAD mRNA in the globus pallidus, and somatostatin mRNA in the entopeduncular nucleus (internal pallidum) ipsilateral to the lesion. In addition, the lesion decreased substance P mRNA in the ipsilateral striatum compared to the contralateral side, and GAD mRNA in the contr alateral entopeduncular nucleus. These effects were abolished in rats with lesions of the subthalamic nucleus and substantia nigra on the sa me side. Thus, the subthalamic lesion prevented changes in gene expres sion induced by dopamine depletion, not only in regions receiving a di rect input from the subthalamic nucleus (ipsilateral pallidum), but al so in regions which do not (striatum and contralateral pallidum). This suggests that polysynaptic pathways regulated by the subthalamic nucl eus contribute to the effects of dopaminergic lesions in many regions of the basal ganglia. This pivotal role of the subthalamic nucleus may account for the beneficial effects of subthalamic nucleus lesions on motor symptoms resulting from dopamine depletion.