Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6810130 | Neurobiology of Aging | 2012 | 11 Pages |
Abstract
Serotonergic 1A (5-HT1A) 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 [3H]-WAY 100,635 autoradiographic receptor binding to measure 5-HT1A 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-HT1A 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-HT1A receptor binding increases in MPTP-vehicle macaques (by 50%, p < 0.05), compared with normal macaques. While 5-HT1A 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-HT1A receptors are involved in the pathophysiology of both parkinsonism and complications of L-DOPA therapy.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Ageing
Authors
Philippe Huot, Tom H. Johnston, James B. Koprich, Lieke Winkelmolen, Susan H. Fox, Jonathan M. Brotchie,