Effects of glutamate receptor antagonists on posthypoxic myoclonus in rats.
Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac arrest and resuscitation. In current studies, roles of N-methyl-D-aspartate (NMDA), non-NMDA (a-amino-3-hydroxy-5-methylisoxazole-4-propionate, AMPA, and kainate), and metabotropic glutamate receptors in the pathophysiology of posthypoxic myoclonus were investigated. Treatments with the competitive or noncompetitive NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D[-]-AP-5) (ED50: 12.5 mg/kg, i.p.) or MK-801 maleate (ED50: 0.034 mg/kg, i.p.), and competitive or noncompetitive non-NMDA (AMPA/kainate) receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (ED50: 9.25 nM/5 microliters, i.c.v.) or 1-(4-ami -nophenyl)-4-methyl-7,8-methylenedioxy -5H-2,3-benzodiazepine hydrochloride (GYKI 52466) (ED50: 0.67 mg/kg, IP), significantly decreased myoclonus episodes in rats. On the other hand, treatment with the metabotropic glutamate receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L[+]-AP-3) (50 or 500 nM/5 microliters, i.c.v., exerted no significant effect on myoclonus scores in posthypoxic rats. These results indicate that activation of NMDA and non-NMDA receptors receptors may mediate posthypoxic myoclonus in rats, whereas, involvement of metabotropic glutamate receptors needs to be studied further.
Jaw
S P
SP
Department of Neurology, University of California Irvine 92717, USA.
Vuong
Q T
QT
Nguyen
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology; D001667:Binding, Competitive; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D002534:Hypoxia, Brain / Q000150:complications*; D008297:Male; D009207:Myoclonus / Q000188:drug therapy* / Q000209:etiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; C061950:GYKI 52466; D001569:Benzodiazepines; C056723:FG 9041; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate