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Neurobiol Aging. 2012 Jan;33(1):207.e9-19. doi: 10.1016/j.neurobiolaging.2010.09.011. Epub 2010 Nov 3.

Regulation of cortical and striatal 5-HT1A receptors in the MPTP-lesioned macaque.

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  • 1Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.

Abstract

Serotonergic 1A (5-HT(1A)) receptor agonists reduce L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia in Parkinson's disease (PD), though the mechanism(s) and site(s) of action remain unclear. We employed [(3)H]-WAY 100,635 autoradiographic receptor binding to measure 5-HT(1A) receptor levels in 4 groups of macaques: normal (vehicle-vehicle); 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned, without exposure to L-DOPA, i.e., untreated parkinsonian (MPTP-vehicle); MPTP-lesioned, receiving a single administration of L-DOPA to alleviate parkinsonism (MPTP-L-DOPA-acute); and MPTP-lesioned, chronically treated with L-DOPA, parkinsonism alleviated but exhibiting dyskinesia (MPTP-L-DOPA-chronic). We demonstrate that 5-HT(1A) receptor binding decreases (by 10%-20%, p < 0.05) in the external layers, but increases (by 80%-100%, p < 0.05) in the middle layers, of the premotor and motor cortex of all MPTP-lesioned macaques. In the striosomes of the caudate nucleus, 5-HT(1A) receptor binding increases in MPTP-vehicle macaques (by 50%, p < 0.05), compared with normal macaques. While 5-HT(1A) receptor binding is low in the matrix of the caudate nucleus in normal macaques, it increases (by 200%, p < 0.05) in MPTP-L-DOPA-chronic macaques. These data suggest that 5-HT(1A) receptors are involved in the pathophysiology of both parkinsonism and complications of L-DOPA therapy.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
21051107
[PubMed - indexed for MEDLINE]
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