BEHAVIORAL-EFFECTS OF 5-HT2C RECEPTOR ANTAGONISM IN THE SUBSTANTIA-NIGRA ZONA RETICULATA OF THE 6-HYDROXYDOPAMINE-LESIONED RAT MODEL OF PARKINSONS-DISEASE

Overactivity of the substantia nigra zona reticulata and the medial se gment of the globus pallidus are responsible for the generation of sym ptoms in Parkinson's disease. Reducing the activity of these regions h as been shown to be a viable alternative to dopamine replacement in th e symptomatic treatment of Parkinson's disease. 5-HT2C receptors in th e substantia nigra zona reticulata are excitatory. In this study we ha ve shown that intracerebral infusion of the selective 5-HT2C receptor antagonist SE 206553 (50 nmol) into the substantia nigra zona reticula ta has an antiparkinsonian action in the 6-hydroxydopamine-lesioned ra t model of Parkinson's disease. SE 206553 did not affect locomotion wh en injected into the nonparkinsonian substantia nigra. Furthermore, we have demonstrated that systemic administration of selective 5-HT2C re ceptor antagonists SE 200646A (20 mg/kg) and SE 206553 (20 mg/kg) can potentiate the antiparkinsonian action of the dopamine D-2 receptor ag onist quinpirole in the 6-hydroxydopamine-lesioned rat. Hence, 5-HT2C receptor antagonists may be useful adjuncts to dopamine agonists in th e treatment of Parkinson's disease. (C) 1998 Academic Press.