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

J Pharmacol Exp Ther. 1993 Oct;267(1):449-55.

Abstract

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • Mice, Inbred ICR
  • Molecular Sequence Data
  • Morphine / pharmacology*
  • Pain Threshold / drug effects*
  • Receptors, Opioid, delta / drug effects
  • Receptors, Opioid, delta / physiology*
  • Receptors, Opioid, mu / physiology
  • Stress, Physiological / physiopathology*
  • Swimming

Substances

  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Morphine