Lesions causing so-called rubral tremors frequently involve the substantia nigra or the nigrostriatal fibers, suggesting dopaminergic denervation as possibly contributory. We examined this hypothesis using PET and [18F]-fluorodopa in six patients with a contralateral tremor following a peduncular lesion. The denervation revealed by PET was even more marked than in severe parkinsonian patients. All patients showed partial to complete improvement with levodopa therapy. PET evaluation of D2-receptors with [76Br]bromolisuride showed no asymmetry of the D2 binding despite the important asymmetry of 18F-fluorodopa uptake. Our results indicate an important involvement of the nigral dopaminergic system in peduncular tremors that appears to be independent of postsynaptic dopamine receptors.

Results suggest that cortical D(2) dopamine receptors are a common target of traditional and atypical antipsychotics for therapeutic action. Higher in vivo binding to the D(2) receptors in the cortex than in the basal ganglia is suggested as an indicator of favourable profile for a putative antipsychotic compound.