title: Hyperdopaminergic status in experimental Huntington disease.
abstract: Huntington disease has been linked to increased dopaminergic neurotransmission in the striatum, and clinical studies have demonstrated that the associated chorea can be treated with dopamine antagonist or dopamine-depleting drugs. The origin of this hyperdopaminergic status is unknown. Because substantia nigra pars compacta and the ventral tegmental area are the main sources of striatal dopamine input, we hypothesized that changes in these regions relate to striatal dopaminergic alterations. Here, in a recently generated transgenic rat Huntington disease model that shows progressive striatal neurodegeneration and chorea, we found evidence of increased dopamine levels in the striatum. We also demonstrate more dopaminergic cells in the substantia nigra pars compacta and ventral tegmental area in these rats. These results suggest that increased striatal dopamine comes from these 2 main nuclei, and that it is not necessarily related to shrinkage of the striatum. The findings implicate increased dopamine input from these nuclei in the pathogenesis of chorea in Huntington disease.
authors: Department of Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
authors: Ali
authors: A
authors: Jahanshahi
authors: Rinske
authors: R
authors: Vlamings
authors: Ahmet Hilmi
authors: AH
authors: Kaya
authors: Lee Wei
authors: LW
authors: Lim
authors: Marcus L F
authors: ML
authors: Janssen
authors: Sonny
authors: S
authors: Tan
authors: Veerle
authors: V
authors: Visser-Vandewalle
authors: Harry W M
authors: HW
authors: Steinbusch
authors: Yasin
authors: Y
authors: Temel
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology*; D008297:Male; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine