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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Riahi, Golnasim Morissette, Marc Parent, Martin Di Paolo, Thérèse
Description	Country affiliation: Canada Author Affiliation: Riahi G ( Faculty of Pharmacy, Laval University, Quebec City, Canada.)
Abstract	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.
File Format	HTM / HTML
ISSN	0953816X
Issue Number	10
Volume Number	33
e-ISSN	14609568
Journal	European Journal of Neuroscience
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2011-05-01
Publisher Place	France
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Neuroscience 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Pharmacology Brain Metabolism Dopamine Agents Dyskinesia, Drug-induced Physiopathology Levodopa Adverse Effects Parkinsonian Disorders Receptor, Serotonin, 5-ht2a Animals Antiparkinson Agents Behavior, Animal Physiology Biogenic Amines Anatomy & Histology Drug Effects Pathology Ergolines Female Humans Ketanserin Therapeutic Use Macaca Drug Therapy Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Neuroscience

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