Publication Type:Journal Article
Source:Biochem Pharmacol, Volume 86, Issue 7, p.970-8 (2013)
Keywords:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Animals, Autoradiography, Basal Ganglia, Behavior, Animal, Benzamides, Brain, Case-Control Studies, Dyskinesia, Drug-Induced, Levodopa, Macaca fascicularis, Parkinson Disease, Pyridines, Receptor, Serotonin, 5-HT1B, Serotonin, Sulfonamides, Thiazoles
L-DOPA-induced dyskinesias (LID)s are abnormal involuntary movements limiting the chronic use of L-DOPA, the main pharmacological treatment of Parkinson's disease (PD). Serotonin receptors are thought to contribute to LID but serotonin 1B (5-HT1B) receptors have never been investigated in any primate models of PD and LID. Therefore, we measured 5-HT1B receptors with [(3)H]GR 125743 autoradiography in controls, MPTP-lesioned monkeys, and L-DOPA-treated MPTP monkeys, with or without Ro 61-8048 treatment, a kynurenine hydroxylase inhibitor alleviating LID. In normal condition, 5-HT1B receptor specific binding was highest in the substantia nigra pars reticulata (SNr), high in the globus pallidus (GP), nucleus accumbens and substantia innominata and lower in the caudate nucleus and putamen. 5-HT1B receptors were increased in caudate nucleus, putamen and SNr of MPTP monkeys compared to controls. L-DOPA-treated MPTP monkeys had elevated 5-HT1B receptor specific binding in caudate nucleus, putamen, SNr and internal GP. In all these brain regions, increases were prevented by co-administration of Ro 61-8048. No effect of MPTP lesion or treatment was observed for 5-HT1B specific binding in the external GP, nucleus accumbens and substantia innominata. This study is the first description in primates of altered brain 5-HT1B receptors associated with prevention of LID.