The dopamine (DA) hypothesis and the asymmetry hypothesis of schizophrenia converge in the possibility that, at least in a subgroup of schizophrenia, DA dysfunction may be asymmetric. Circling behavior in animals is mediated through a final common DA pathway. Rotational preference in humans is a newly described subtle clinical neurological sign. It is probably akin to hemispatial-neglect in neurological patients and to circling behavior in animals. Both hemi-neglect and circling have been specifically associated with asymmetry of DA attentional and motor pathways, and with striatal, prefrontal and inferior parietal lesions. Animals, as a rule, neglect-to-rotate toward the hemisphere with higher striatal DA activity, regardless of physical surroundings. DA receptor agonists AS A RULE induce preferential rotation AWAY FROM lesions (e.g. unilateral prefrontal lesions) that causes ipsilateral increase in the number of striatal DA receptors. A direct means of seeking human analogues of circling behavior was not previously available. A belt-mounted electronic rotometer, has been designed by the PI so that its output is determined by precisely the same logic employed with the circling apparatus commonly used to study rodents. The studies proposed here will use this novel automated instrument. We will record rotational behavior in unmedicated and never-medicated symptomatic schizophrenic patients. To test the hypothesis that a subgroup within the schizophrenic syndrome has dys-regulated asymmetric supersensitivity (right > left) of the striatal DA receptors. We will ask: a. Is there at least a subgroup within the schizophrenic syndrome that has clinical evidence of asymmetric DA dysfunction; a spontaneous left-prone rotational preference compares to controls? b. Will a bromocriptine challenge accentuate this neglect of right-sided turning exhibited by unmedicated schizophrenic patients?
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