Increased [I-125]sulpiride binding in the subthalamic nucleus of rats withnigrostriatal lesions

SUBTHALAMIC nucleus (STN) hyperactivity follows lesions of mesencephalic do paminergic neurons in animal models of Parkinson's disease. The mechanism l eading to sustained STN hyperactivity in parkinsonism is not well understoo d, but it seems not to depend on the integrity of striato-pallido-subthalam ic connections (the so called indirect pathway). Sustained STN hyperactivit y could result from the loss of the direct dopaminergic innervation of the STN. Here we report increased [I-125]sulpiride binding in the STN of rats w ith 6-hydroxydopamine (6-OHDA) lesions of mesencephalic dopaminergic neuron s. Furthermore, we found that chronic oral treatment with levodopa reverted the lesion-induced increase in [I-125]sulpiride binding. Our results demon strate that most STN D2-class dopamine receptors are postsynaptic to affere nt dopaminergic fibers. Furthermore, they suggest that alterations of local STN dopaminergic mechanisms could play a role in the pathophysiology of pa rkinsonism and mediate the therapeutic/adverse effects of chronic levodopa administration. NeuroReport 10:1501-1505 (C) 1999 Lippincott Williams & Wil kins.