Modulation of morphine antinociception by swim-stress in the mouse: involvement of supraspinal opioid delta-2 receptors

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 267; no. 1; pp. 449 - 455
• Main Authors: VANDERAH, T. W, WILD, K. D, TAKEMORI, A. E, SULTANA, M, PORTOGHESE, P. S, BOWEN, W. D, HRUBY, V. J, MOSBERG, H. I, PORRECA, F
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.10.1993
• Subjects: Amino Acid Sequence; Analgesics; Animals; Biological and medical sciences; Dose-Response Relationship, Drug; Male; Medical sciences; Mice; Mice, Inbred ICR; Molecular Sequence Data; Morphine - pharmacology; Neuropharmacology; Pain Threshold - drug effects; Pharmacology. Drug treatments; Receptors, Opioid, delta - drug effects; Receptors, Opioid, delta - physiology; Receptors, Opioid, mu - physiology; Stress, Physiological - physiopathology; Swimming; Nociception; Opiate receptor δ; Rodentia; Morphine; Opiates; Cerebral ventricle; Narcotic analgesic; Stress; Analgesia; Vertebrata; Mammalia; Pain; Mouse; Animal; Modulation; Intracerebral administration; Mechanism of action
• ISSN: 0022-3565; 1521-0103

The present study evaluated the effect of a brief exposure of mice to cold-water swim-stress (CWSS) on the antinociceptive potency of i.c.v. given morphine. No significant antinociceptive response could be demonstrated in the warm-water tail-flick test, 10 min after a 30-sec exposure of mice to water at 5 degrees C. However, the i.c.v. morphine dose-response curve in mice exposed to CWSS was displaced significantly to the left when compared to that obtained in control (i.e., non-CWSS-exposed) mice. Although coadministration of the delta antagonist, N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH 1 (ICI 174,864), with i.c.v. morphine did not produce antagonism of the antinociceptive action of this mu opiate, the leftward displacement of the i.c.v. morphine dose-response curve seen in CWSS-exposed mice was blocked in ICI 174,864-treated mice suggesting involvement of opioid delta receptors in the modulatory effect. Pretreatment of mice with the delta-1 antagonist, [D-Ala2, Leu5, Cys6] enkephalin, did not antagonize the antinociception of morphine and further did not antagonize the leftward displacement produced by exposure to CWSS. Pretreatment of mice with the delta-2 antagonist, 5'-isothiocyanate, also did not antagonize the antinociceptive effects of morphine but blocked the leftward displacement in the morphine dose-response curve associated with CWSS, suggesting involvement of an opioid delta-2 receptor in this effect. Pretreatment of mice with the mu antagonist, beta-funaltrexamine, produced a significant antagonism of the morphine antinociceptive effect as seen by a rightward displacement of the morphine dose-effect curve.