Opposite effects of NMDA and AMPA receptor blockade on catalepsy induced by dopamine receptor antagonists.
Excitatory amino acid antagonists have been proposed as novel therapeutic agents for Parkinson's disease due to their ability to reverse akinesia in animal models of this disorder. To further evaluate this therapeutic potential, we examined the effects of a N-methyl-D-aspartate (NMDA) and an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist on catalepsy produced by dopamine D1 or D2 receptor antagonists in rats. Male Sprague-Dawley rats were injected with dizocilpine (MK-801 0.025, 0.05 or 0.1 mg/kg i.p.), 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX 12.5 mg/kg i.p.) or saline prior to administration of either raclopride (2.5 mg/kg i.p.) or SCH 23390 (0.5 mg/kg i.p.). Catalepsy was evaluated with both grid and bar tests every 20 min for 2.7 h. MK-801 (0.1 mg/kg) reversed the catalepsy produced by either raclopride or SCH 23390 but did not stimulate locomotion when given alone at this dose. At 0.05 mg/kg, MK-801 markedly decreased SCH 23390-induced catalepsy, but did not affect the catalepsy produced by raclopride. In contrast, NBQX increased raclopride-induced catalepsy, but had no effect on catalepsy elicited by SCH 23390. These findings suggest that blockade of NMDA receptors, but not non-NMDA receptors, may reverse the catalepsy produced by dopamine receptor antagonists.
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892.
S M
SM
Papa
T M
TM
Engber
R C
RC
Boldry
T N
TN
Chase
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D012457:Salicylamides; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D020891:Raclopride; D016291:Dizocilpine Maleate