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TW Vanderah, KD Wild, AE Takemori, M Sultana, PS Portoghese, WD Bowen, VJ Hruby, HI Mosberg and F Porreca
Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.
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)
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