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The Journal of Neuroscience, July 1, 2000, 20(13):5170-5178

Nigrostriatal Lesions Alter Oral Dyskinesia and c-Fos Expression Induced by the Serotonin Agonist 1-(m-Chlorophenyl)piperazine in Adult Rats

Philippe De Deurwaerdère and Marie-Françoise Chesselet

Department of Neurology, University of California, Los Angeles School of Medicine, Los Angeles, California 90095

The loss of dopaminergic innervation of the basal ganglia, a group of subcortical regions involved in motor control, is the hallmark of Parkinson's disease. The resulting molecular and cellular alterations mediate behavioral deficits and may modify neuronal responses to other neurotransmitters. In the present study, we sought to determine the effects of chronic dopamine (DA) depletion on responses mediated by stimulation of serotonergic 2C (5-HT_2C) receptors, a serotonergic receptor subtype present in discrete regions of the basal ganglia. Specifically, the effects of unilateral lesions of nigrostriatal DA neurons on oral dyskinesia and Fos protein expression induced by the non-selective 5-HT_2C agonist 1-(m-chlorophenyl)piperazine (m-CPP) were examined.

Confirming previous findings, both peripheral and local injections of m-CPP into the subthalamic nucleus elicited oral dyskinesia. Nigrostriatal lesions markedly enhanced oral bouts induced by peripheral but not intrasubthalamic administration of m-CPP. In intact rats, Fos expression was increased by m-CPP (1 mg/kg, i.p.) in the striatum and the subthalamic nucleus. After nigrostriatal lesions, m-CPP-induced Fos expression remained unchanged in the subthalamic nucleus but was reduced in the medial quadrants of the striatum and was markedly enhanced in the entopeduncular nucleus. These data demonstrate regionally specific alterations in behavioral and cellular responses to a serotonergic agonist in an animal model of Parkinson's disease.

Key words: Parkinson's disease; dyskinesia; dopamine; serotonin; basal ganglia; serotonin 2C receptors; c-Fos; m-CPP

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20135170-09$05.00/0

This article has been cited by other articles:

				P. De Deurwaerdere, S. Navailles, K. A Berg, W. P. Clarke, and U. Spampinato Constitutive Activity of the Serotonin2C Receptor Inhibits In Vivo Dopamine Release in the Rat Striatum and Nucleus Accumbens J. Neurosci., March 31, 2004; 24(13): 3235 - 3241. [Abstract] [Full Text] [PDF]

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