Pharmacology
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In male Sprague-Dawley rats, acute and chronic effects of dizocilpine (MK-801), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, were determined on the analgesic and hypothermic actions of U-50,488H, a kappa-opioid receptor agonist. In addition, the in vitro effects of MK-801 on the binding of [3H]ethylketocyclazocine ([3H]EKC) to kappa-opioid receptors in brain and spinal cord of the rat were determined. A single injection of MK-801 given 10 min prior to U-50,488H or given twice a day for 4 days dose-dependently enhanced the analgesic action of U-50,488H. ⋯ On the other hand, chronic treatment with MK-801 decreased the Kd of [3H]EKC binding in spinal cord without affecting Bmax. It is concluded that blockade of NMDA receptor enhances the analgesic response to a kappa-opioid receptor agonist and upregulates brain and spinal cord kappa-opioid receptors. Finally, the results suggest that the NMDA receptor may have a role in the regulation of kappa-opioid systems.