NBQX BLOCKS ACUTE AND LATE EPILEPTOGENIC EFFECTS OF PERINATAL HYPOXIA

Clinically, and in experimental models, perinatal hypoxic encephalopat hy is commonly associated with seizures. We previously described a rat model in which hypoxia induces seizures and permanently increases in seizure susceptibility in immature rats [postnatal day (P) 10-12] but not in older rats. In the present study, we compared the effect of pre treatment with the excitatory amino acid antagonists MK-801 and NBQX v ersus lorazepam in our rat model of perinatal hypoxia. Animals exposed to hypoxia at P10 without treatment have frequent seizures during hyp oxia and subsequently exhibit increased seizure susceptibility to flur othyl. Treatment with 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX 20 mg/kg) effectively suppressed hypoxia-induced seizures in im mature rats and also protected against permanent changes in flurothyl threshold in adulthood, whereas treatment with MK-801 (1 mg/kg) or lor azepam (LZP I mg/kg) did not prevent these hypoxia-related epileptogen ic effects. These results suggest that activation of alpha-amino-3-hyd roxy-5-methyl-4-isoxazol propionic acid (AMPA) receptors may partly me diate the age-dependent epileptogenic effect of hypoxia in the perinat al period.