Antinociceptive interactions of opioid delta receptor agonists with morphine in mice: supra- and sub-additivity

• Published in: Life sciences (1973) Vol. 50; no. 20; p. 1535
• Main Authors: Horan, P, Tallarida, R J, Haaseth, R C, Matsunaga, T O, Hruby, V J, Porreca, F
• Format: Journal Article
• Language: English
• Published: Netherlands 1992
• Subjects: Analgesics - pharmacology; Animals; Drug Synergism; Enkephalin, D-Penicillamine (2,5); Enkephalin, Methionine - pharmacology; Enkephalins - pharmacology; Male; Mice; Mice, Inbred ICR; Morphine - pharmacology; Oligopeptides - pharmacology; Receptors, Opioid - drug effects; Receptors, Opioid, delta
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/0024-3205(92)90144-E

In this study, the antinociceptive interactions of fixed ratio combinations of intracerebroventricularly (i.c.v.) given morphine and subantinociceptive doses of the delta agonists, [D-Pen2, D-Pen5]enkephalin (DPDPE), [D-Ala2, Glu4]deltorphin (DELT) or [Met5]enkephalin (MET) were examined using the mouse warm water tail flick test. When morphine was coadministered with DPDPE or DELT in a 4:1 and 9:1 mixture, respectively, a synergistic antinociceptive effect was observed. In contrast, when morphine was coadministered with MET in a 1:2 fixed ratio mixture, a subadditive interaction occurred. These results demonstrate both positive and negative modulatory interactions of delta agonists with morphine in an antinociceptive endpoint and that these interactions can be either supra- or subadditive. The data support the concept of a functional interaction between opioid mu and delta receptors and a potential regulatory role for the endogenous ligands of the opioid delta receptor.