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

Peter Horan, Ronald J. Tallarida, Ronald C. Haaseth, Terry O. Matsunaga, Victor J. Hruby, Frank Porreca

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


In this study, the antinociceptive interactions of fixed ratio combinations of intracerebroventricularly (i.c.v.) given morphine and subantinociceptive doses of the δ 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 δ 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 μ and δ receptors and a potential regulatory role for the endogenous ligands of the opioid δ receptor.

Original languageEnglish (US)
Pages (from-to)1535-1541
Number of pages7
JournalLife Sciences
Issue number20
StatePublished - 1992

ASJC Scopus subject areas

  • General Pharmacology, Toxicology and Pharmaceutics
  • General Biochemistry, Genetics and Molecular Biology


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