Opioid delta-receptor involvement in supraspinal and spinal antinociception in mice

Abstract

The possibility that the opioid delta-receptor mediates antinociception in tests where heat is the noxious stimulus was investigated using highly selective mu- and delta-agonist and -antagonists. Antinociceptive dose-response curves were constructed for mu ([D-Ala2,NMePhe4,Gly-ol]enkephalin, DAGO; morphine) and delta ([D-Pen2,D-Pen5]enkephalin, DPDPE)-agonists in the absence, and in the presence of the mu non-surmountable antagonist, beta-funaltrexamine (beta-FNA) or the delta-antagonist ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH, where Aib is alpha-amino-isobutyric acid). Agonists and ICI 174,864 were given alone in the same intracerebroventricular (i.c.v.) or intrathecal (i.th.) injection to mice 20 min prior to testing in the warm-water (55 degrees C) tail-withdrawal test (+10 min for i.th. DPDPE); beta-FNA was given as a single i.c.v. or i.th. pretreatment dose (20 and 0.01 nM, respectively) 4 h prior to testing. I.c.v. pretreatment with beta-FNA resulted in a rightward displacement of the DAGO and morphine antinociceptive dose-response lines, but failed to displace the i.c.v. DPDPE curve. Similarly, i.th. pretreatment with beta-FNA displaced the i.th. morphine dose-response curve to the right without affecting the i.th. DPDPE antinociceptive dose-response line. ICI 174,864 (1 and 3 micrograms) produced a dose-related antagonism of i.c.v. or i.th. DPDPE, but did not alter the antinociceptive effects of DAGO or morphine given by the same routes. Co-administration of ICI 174,864 (3 micrograms) with i.c.v. morphine in beta-FNA pretreated (but not control) mice resulted in a further rightward displacement of the morphine dose-response line.(ABSTRACT TRUNCATED AT 250 WORDS)