Differential potentiative effects of glutamate receptor antagonists in the production of antinociception induced by opioids administered intrathecally in the mouse.
The effect of (+/-)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5, 10-imine maleate (MK-801) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) injected intrathecally (i.t.) on the inhibition of the tail-flick response induced by morphine, D-Ala(2)-NmePhe(4)-Gly-ol-enkephalin (DAMGO), beta-endorphin, D-Pen(2,5)-enkephalin (DPDPE), or ¿(trans-3, 4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeocetamide)¿ (U50, 488H) administered i.t. was studied in ICR mice. The i.t. injection of MK-801 (2 microg) or CNQX (1 microg) alone did not affect the basal tail-flick response. Morphine (0.2 microg), DAMGO (0.8 ng), beta-endorphin (0.1 microg), DPDPE (0.5 microg) or U50, 488H (6 microg) caused only slight inhibition of the tail-flick response. CNQX injected i.t., but not MK-801, enhanced the inhibition of the tail-flick response induced by i.t. administered morphine, DAMGO, DPDPE or U50, 488H. However, CNQX or MK-801 injected i.t. was not effective in enhancing the inhibition of the tail-flick response induced by beta-endorphin administered 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 microg), yohimbine (from 1 to 20 microg) or methysergide (from 1 to 20 microg) injected i.t. in a dose-dependent manner. Our results suggest that the blockade of AMPA/kainate receptors located in the spinal cord appears to be involved in enhancing the inhibition of the tail-flick response induced by stimulation of spinal mu-, delta-, and kappa-opioid receptors. Furthermore, this potentiating action may be mediated by spinal noradrenergic and serotonergic receptors. However, N-methyl-D-aspartate receptors may not be involved in modulating the inhibition of the tail-flick response induced by various opioids administered spinally.
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Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, South Korea. hwsuh@sun.hallym.ac.kr
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Huh
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Kim
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D001615:beta-Endorphin / Q000494:pharmacology
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D020881:Enkephalin, D-Penicillamine (2,5)-