TY - JOUR
T1 - Antinociceptive interactions of opioid delta receptor agonists with morphine in mice
T2 - Supra- and sub-additivity
AU - Horan, Peter
AU - Tallarida, Ronald J.
AU - Haaseth, Ronald C.
AU - Matsunaga, Terry O.
AU - Hruby, Victor J.
AU - Porreca, Frank
N1 - Funding Information:
This work was supported by USPHS Grants from the National Institute on Drug Abuse. P.J.H. is the recipient of a NIDA Postdoctoral Fellowship (DA 05395).
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
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U2 - 10.1016/0024-3205(92)90144-E
DO - 10.1016/0024-3205(92)90144-E
M3 - Article
C2 - 1315897
AN - SCOPUS:0026550559
SN - 0024-3205
VL - 50
SP - 1535
EP - 1541
JO - Life Sciences
JF - Life Sciences
IS - 20
ER -