Glycine site antagonists abolish dopamine D2 but not D1 receptor mediated catalepsy in rats.
Catalepsy--a state of postural immobility (akinesia) with muscular rigidity (rigor)--and reduced locomotion in animals are behavioral deficits showing similarities with symptoms of Parkinson's disease (PD). The effects of the glycine site antagonists 7-chlorokynurenate and (R)-HA-966 on haloperidol-(D 2 antagonist) and SCH 23390- (D 1 antagonist) induced catalepsy and reduced locomotion are investigated in rats. Both antagonists dose-dependently counteract dopamine D 2 receptor mediated catalepsy but they have no influence on locomotion. Neither 7-chlorokynurenate nor (R)-HA-966 has any effect on dopamine D 1 receptor mediated catalepsy. This finding is surprising, since NMDA receptor antagonists counteract both, dopamine D 1 and D 2 receptor mediated catalepsy. D 1 and D 2 receptors are located on different populations of neurons. Thus, the present findings suggest that these different neuronal populations have different sensitivity for ligands binding at the glycine binding site of the NMDA receptor.
Kretschmer
B D
BD
Department of Neuropharmacology, University of Tübingen, Federal Republic of Germany.
Winterscheid
B
B
Danysz
W
W
Schmidt
W J
WJ
D000818:Animals; D001552:Benzazepines / Q000633:toxicity; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006220:Haloperidol / Q000633:toxicity; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology
D001552:Benzazepines; D011760:Pyrrolidinones; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C001369:1-hydroxy-3-amino-2-pyrrolidone; D007736:Kynurenic Acid; D006220:Haloperidol; C057013:7-chlorokynurenic acid