Differential potentiative effects of glutamate receptor antagonists in theproduction of antinociception induced by opioids administered intrathecally in the mouse

The effect of (+/-)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5, 1 0-imine maleate (MK-801) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inj ected intrathecally (i.t.) on the inhibition of the tail-flick response ind uced by morphine, D-Ala(2)-NmePhe(4)-Gly-olI-enkephalin (DAMGO), p-endorphi n, beta-endorphin, D-Pen(2,5)-enkephalin (DPDPE), or {(trans-3,4-dichloro-N -methyl-N-[2-(1- pyrrolidinyl) cyclohexyl] benzeocetamide)} (U50, 488H) adm inistered i.t. was studied in ICR mice. The i.t. injection of MK-801 (2 mu g) or CNQX(1 Erg) alone did not affect the basal tail-flick response. Morph ine (0.2 mu g), DAMGO (0.8 ng), p-endorphin (0.1 mu g), DPDPE (0.5 CLS) or U50, 488H (6 mu g) caused only slight inhibition of the tail-flick response . CNQX injected i.t., but not MK-801, enhanced the inhibition of the tail-f lick response induced by i.t. administered morphine, DAMGO, DPDPE or U50, 4 88H. However, CNQX or MK-801 injected i.t. was not effective in enhancing t he inhibition of the tail-flick response induced by P-endorphin administere d i.t. The potentiating effect of CNQX on tail-flick inhibition induced by morphine, DAMGO, DPDPE or U50, 488H was blocked by naloxone (from 1 to 20 m u g), yohimbine (from 1 to 20 mu g) or methysergide (from 1 to 20 mu g) inj ected i.t. in a dose-dependent manner. Our results suggest that the blockad e of AMPA/kainate receptors located in the spinal cord appears to be involv ed in enhancing the inhibition of the tail-flick response induced by stimul ation of spinal mu-, delta-, and kappa-opioid receptors. Furthermore, this potentiating action may be mediated by spinal noradrenergic and serotonergi c receptors. However, N-methyl-D-aspartate receptors may not be involved in modulating the inhibition of the tail-flick response induced by various op ioids administered spinally. (C) 2000 Elsevier Science Inc.