Changes in striatal dopamine D3 receptor regulation during expression of and recovery from MPTP-induced parkinsonism.
Striatal dopamine (DA) D3 receptor density (measured by quantitative receptor autoradiography) and mRNA expression (measured by reverse transcriptase-polymerase chain reaction) were analyzed in cats symptomatic for and recovered from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. In symptomatic cats, D3 receptor density was significantly decreased in all regions of the caudate nucleus (CD) (66--77%), the nucleus accumbens (NACC) (52--83%) and the islands of calleja (IC) (67%), all of which returned to normal values in recovered cats. In contrast, D3 receptor mRNA expression was slightly elevated in symptomatic cats, and significantly increased above normal in recovered cats (45% increase in the CD and 91% in the NACC). Thus, reduction of parkinsonian signs was related to normalization of striatal D3 receptor number. These alterations in D3 receptor expression may play an important role in the recovery process observed in this model of parkinsonism.
Wade
T V
TV
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, JAH 521, Philadelphia, PA 19107, USA.
Rothblat
D S
DS
Schneider
J S
JS
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence / Q000502:physiology; D002415:Cats; D018076:DNA, Complementary / Q000737:chemistry / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D020127:Recovery of Function / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
D018076:DNA, Complementary; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D004298:Dopamine