Effects of competitive and noncompetitive antagonists of the N-methyl-D-aspartate receptor on the analgesic action of delta 1- and delta 2-opioid receptor agonists in mice.

1. The effects of MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and LY 235959, a competitive antagonists of the NMDA receptor on the analgesic actions of [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2, Glu4] deltorphin II (deltorphin II), the putative delta 1- and delta 2-opioid receptor agonists, respectively, were determined in the male Swiss-Webster mice. 2. Intracerebroventricular administration of DPDPE or deltorphin II produced analgesia. MK-801 administered intraperitoneally 10 min before the injection of DPDPE or deltorphin II, dose-dependently antagonized the analgesic actions of both drugs. 3. LY 235959 also dose-dependently antagonized the analgesic actions of DPDPE and deltorphin II. 4. The effects of MK-801 and LY 235959 on the binding of [3H]-DPDPE to mouse brain membranes were also determined. Neither of the NMDA receptor antagonists had any effect on the binding of [3H]-DPDPE. 5. It is concluded that competitive and noncompetitive antagonists of the NMDA receptor antagonize the analgesic action of delta 1- and delta 2-opioid receptor agonists and that such effects are not mediated via a direct interaction with brain delta-opioid receptors.