Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists

CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline), two competitive AMPA (non-NMDA glutamate) receptor antagonists, as well as their interaction with CGP 37849, a competitive NMDA receptor antagonist, were studied in rats and mice. CNQX and NBQX inhibited the locomotor activity of naive rats. No symptoms of behavioral excitation were observed. CGP 37849 induced locomotor hyperactivity which was reduced by CNQX and NBQX. In monoamine-depleted rats (pretreated with reserpine + alpha-methyl-p-tyrosine), none of the two quinoxalines nor CGP 37849 antagonized akinesia. The antiakinetic effect of L-DOPA was increased by CGP 37849, but not by CNQX or NBQX. The latter action of CGP 37849 was decreased by CNQX and NBQX. The antiakinetic effect of clonidine was not changed by CNQX. The locomotor hyperactivity induced by apomorphine or cocaine was not modified by CNQX. Neither of the quinoxalines changed the catalepsy induced by haloperidol or spiperone. The fluphenazine catalepsy was slightly decreased by CNQX and increased by NBQX. CNQX and NBQX were inactive in the forced swimming test; CNQX (but not NBQX) increased the CGP 37849-induced reduction of the immobility time. CNQX decreased the muscle tone of hind limbs in naive and monoamine-depleted rats. The obtained results indicate that the AMPA receptor antagonists differ in their neuropharmacological profile from CGP 37849, an NMDA receptor antagonist. There is no positive cooperation (except for the forced swimming test) between NMDA and AMPA receptor antagonists; on the contrary, an antagonistic between them has been observed.