EFFECTS OF GLUTAMATE-RECEPTOR ANTAGONISTS ON POSTHYPOXIC MYOCLONUS INRATS

Male Sprague-Dawley rats developed posthypoxic myoclonus following 10- min cardiac arrest and resuscitation. In current studies, roles of N-m ethyl-D-aspartate (NMDA), non-NMDA (a-amino-3-hydroxy-5-methylisoxazol e-4-propionate AMPA, and kainate), and metabotropic glutamate receptor s in the pathophysiology of posthypoxic myoclonus were investigated. T reatments with the competitive or noncompetitive NMDA receptor antagon ist, D(-)-2-amino-5-phosphonopentanoic acid (D[-]-AP-5) (ED(50): 12.5 mg/kg, IP) or MK-801 maleate (ED(50): 0.034 mg/kg, IP), and competitiv e or noncompetitive non-NMDA (AMPA/kainate) receptor antagonist, 6,7-d initroquinoxaline-2, 3-dione (DNQX) (ED(50): 9.25 nM/5 mu l, ICV) or 1 -(4-ami-nophenyl)-4-methyl-7, 8-methylenedioxy-5H-2, 3-benzodiazepine hydrochloride (GYKI 52466) (ED(50): 0.67 mg/kg, IP), significantly dec reased myoclonus episodes in rats. On the other hand, treatment with t he metabotropic glutamate receptor antagonist, L(+)-2-amino-3-phosphon opropionic acid (L[+]-AP-3) (50 or 500 nM/5 mu l, ICV), exerted no sig nificant effects on myoclonus scores in posthypoxic rats. These result s indicate that activation of NMDA and non-NMDA receptors receptors ma y mediate posthypoxic myoclonus in rats, whereas, involvement of metab otropic glutamate receptors needs to be studied further.