Effect of L-Dopa on metabotropic glutamate receptor 5 in the brain of parkinsonian monkeys.
Behavioral investigations of selective and potent metabotropic glutamate receptor type 5 (mGluR5) antagonists in animal models suggest involvement of mGluR5 in compensatory mechanisms of the basal ganglia circuitry in Parkinson's disease and levodopa (L-Dopa) induced motor complications. This study investigated mGluR5 changes in MPTP lesioned monkeys. The effect of a chronic 1 month treatment with L-Dopa on mGluR5-specific binding and mRNA levels was investigated in MPTP monkeys killed 4 or 24 h after their last L-Dopa administration. [(3)H]ABP688 specific binding in the putamen was elevated in L-Dopa-treated MPTP monkeys killed 24 h but not 4 h after their last L-Dopa dose compared with vehicle-treated MPTP monkeys. Caudate nucleus [(3)H]ABP688-specific binding was elevated in both groups of L-Dopa treated compared with vehicle-treated MPTP monkeys. In contrast, caudate nucleus and putamen mGluR5 mRNA levels were elevated only in L-Dopa-treated MPTP monkeys killed 4 h after their last L-Dopa administration. MPTP monkeys killed 4 h after their last L-Dopa treatment showed higher caudate nucleus and putamen L-Dopa concentrations compared with those killed after 24 h. Hence, mGluR5 in the putamen are sensitive to presence of L-Dopa leading to a rapid decrease of [(3)H]ABP688-specific binding possibly involving a direct mGluR5/dopamine receptors interaction.
Molecular Endocrinology and Genomic Research Center, Laval University Medical Center (CHUL), Quebec, Canada.
Bazoumana
B
Ouattara
Fabrizio
F
Gasparini
Marc
M
Morissette
Laurent
L
Grégoire
Pershia
P
Samadi
Baltazar
B
Gomez-Mancilla
Thérèse
T
Di Paolo
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001345:Autoradiography; D001679:Biogenic Amines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003627:Data Interpretation, Statistical; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D017403:In Situ Hybridization; D007980:Levodopa / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000378:metabolism*; D008252:Macaca fascicularis; D010052:Ovariectomy; D010091:Oximes / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000378:metabolism*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D012110:Reserpine / Q000494:pharmacology
C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D000978:Antiparkinson Agents; D001679:Biogenic Amines; D002395:Catecholamines; D050483:Dopamine Plasma Membrane Transport Proteins; D010091:Oximes; D011725:Pyridines; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D007980:Levodopa; D012110:Reserpine