INFLUENCE OF COMBINED TREATMENT WITH NMDA AND NON-NMDA RECEPTOR ANTAGONISTS ON ELECTROCONVULSIONS IN MICE

-3-hydroxy-5-methyl-isoxazole-4-propionate/kainate (AMPA/kainate) rece ptor antagonists (at subthreshold doses against electroconvulsions), - 4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466 at maxim ally 5 mg/kg) and 3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline ( NBQX at maximally 20 mg/kg) enhanced the protective effects of NMDA re ceptor antagonists, MK-801 (dizocilpine) or (2-carboxypiperazine-4-yl) -1-propenyl-1-phosphonic acid (D-CPP-ene), against electroconvulsions. Similarly, MK-801 or D-CPP-ene reduced the ED,, values of both NBQX a nd GYKI 52466 against maximal electroshock. The adverse effects of D-C PP-ene, evaluated in the chimney and rotorod tests, were potentiated b y both GYKI 52466 (2.5 mg/kg) and NBQX (10 mg/kg). Also, D-CPP-ene (0. 1 mg/kg) worsened the motor performance of mice pretreated with GYKI 5 2466 in the rotorod test. Neither MK-801 (0.025 mg/kg) nor D-CPP-ene ( 0.1 mg/kg) affected the NBQX-induced impairment of motor coordination. Similarly, GYKI 52466 (2.5 mg/kg) or NBQX (10 mg/kg) did not influenc e the performance of mice treated with MK-801 (0.2 mg/kg). It may be c oncluded that the blockade of more than one subtype of glutamate recep tors leads to a more pronounced anticonvulsive effect when compared wi th the effect of blockade of an individual receptor subtype. In some c ases more efficient seizure protection was not associated with increas ed adverse effects.