PT  - JOURNAL ARTICLE
AU  - Michael R. Brandt
AU  - S. Stevens Negus
AU  - Nancy K. Mello
AU  - M. Scott Furness
AU  - Xiaoyan Zhang
AU  - Kenner C. Rice
TI  - Discriminative Stimulus Effects of the Nonpeptidic δ-Opioid Agonist SNC80 in Rhesus Monkeys
DP  - 1999 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1157--1164
VI  - 290
IP  - 3
4099  - http://jpet.aspetjournals.org/content/290/3/1157.short
4100  - http://jpet.aspetjournals.org/content/290/3/1157.full
SO  - J Pharmacol Exp Ther1999 Sep 01; 290
AB  - Five rhesus monkeys were trained to discriminate the nonpeptidic, δ-opioid agonist SNC80 (0.32 mg/kg i.m.) from saline by using a food-reinforced drug-discrimination procedure. Cumulative doses of SNC80 produced a dose-dependent increase in SNC80-appropriate responding and a dose-dependent decrease in response rate. In time-course studies, peak effects of the training dose of SNC80 were observed after 15 min, and these effects diminished over 240 min. In substitution studies, other piperazinyl benzamide δ agonists (SNC86, SNC162, and SNC243A) substituted for SNC80 with relative potencies similar those of SNC80. However, SNC67, the (−)-enantiomer of SNC80, did not occasion SNC80-appropriate responding up to a dose (32.0 mg/kg) that produced convulsions in one monkey. The μ agonists morphine and fentanyl and the κ agonists U-50,488 and enadoline failed to substitute for SNC80 up to doses that eliminated responding. Two nonopioids (the N-methyl-d-aspartate antagonist ketamine and the monoamine reuptake inhibitor cocaine) also produced primarily saline-appropriate responding. Both the discriminative stimulus and rate-decreasing effects of SNC80 were antagonized by the δ-selective antagonist naltrindole (0.01–1.0 mg/kg) but not by doses of the opioid antagonist quadazocine (0.1–1.0 mg/kg) that block the effects of μ and κ agonists. These data suggest that the discriminative stimulus effects of SNC80 are mediated by δ-opioid receptors and that the discriminative stimulus effects of δ opioids in primates can be differentiated from the effects of other opioid and nonopioid compounds. The American Society for Pharmacology and Experimental Therapeutics