Abstract
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.
Footnotes
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Send reprint requests to: Michael R. Brandt, Ph.D. Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, 115 Mill St., Belmont, MA. E-mail:mbrandt{at}hms.harvard.edu
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↵1 These studies were supported in part by Grants RO1-DA02519, P50-DA04059, T32-DA0752, and KO5-DA00101 from the National Institute on Drug Abuse, National Institutes of Health. We also thank the National Institute on Drug Abuse for partial support for the Laboratory of Medicinal Chemistry, National Institute of Diabetics, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD.
- Abbreviations:
- EKC
- ethylketocyclazocine
- % DR
- percent drug responding
- DPDPE
- [d-Pen2-d-Pen5]enkephalin
- Received March 11, 1999.
- Accepted May 7, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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