Brain 5-HT(2A) receptors in MPTP monkeys and levodopa-induced dyskinesias.

Golnasim Riahi, Marc Morissette, Martin Parent, Thérèse Di Paolo

Faculty of Pharmacy, Laval University, Quebec City, Canada.

The European journal of neuroscience 2011 May

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Levodopa-induced dyskinesias (LIDs) are abnormal involuntary movements induced by the chronic use of levodopa (l-Dopa) limiting the quality of life of Parkinson's disease (PD) patients. We evaluated changes of the serotonin 5-HT(2A) receptors in control monkeys, in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys and in l-Dopa-treated MPTP monkeys, without or with adjunct treatments to inhibit the expression of LID: CI-1041, a selective NR1A/2B subunit antagonist of glutamate N-methyl-d-aspartic acid (NMDA) receptor, or Cabergoline, a long-acting dopamine D(2) receptor agonist. All treatments were administered for 1 month and animals were killed 24 h after the last dose of l-Dopa. Striatal concentrations of serotonin were decreased in all MPTP monkeys investigated, as measured by high-performance liquid chromatography. [(3) H]Ketanserin-specific binding to 5-HT(2A) receptors was measured by autoradiography. l-Dopa treatment that induced dyskinesias increased 5-HT(2A) receptor-specific binding in the caudate nucleus and the anterior cingulate gyrus (AcgG) compared with control monkeys. Moreover, [(3) H]Ketanserin-specific binding was increased in the dorsomedial caudate nucleus in l-Dopa-treated MPTP monkeys compared with saline-treated MPTP monkeys. Nondyskinetic monkeys treated with CI-1041 or Cabergoline showed low 5-HT(2A) -specific binding in the posterior dorsomedial caudate nucleus and the anterior AcgG compared with dyskinetic monkeys. No significant difference in 5-HT(2A) receptor binding was observed in any brain regions examined in saline-treated MPTP monkeys compared with control monkeys. These results confirm the involvement of serotonergic pathways and the glutamate/serotonin interactions in LID. They also support targeting 5-HT(2A) receptors as a potential treatment for LID. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Citation

Golnasim Riahi, Marc Morissette, Martin Parent, Thérèse Di Paolo. Brain 5-HT(2A) receptors in MPTP monkeys and levodopa-induced dyskinesias. The European journal of neuroscience. 2011 May;33(10):1823-31