Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys

Psychopharmacology (Berl). 1996 Feb;123(4):320-4. doi: 10.1007/BF02246641.

Abstract

The antagonist effects of clocinnamox were evaluated against opioid agonists, acting at mu, kappa and delta-receptors, in rhesus monkeys (n = 3-4) responding under a fixed-ratio 30 (FR 30) schedule for food delivery. Clocinnamox (0.032-0.1 mg/kg) dose-dependently antagonized fentanyl (0.001-0.32 mg/kg) after either a 3-h or 1-day pretreatment; there was substantial recovery of agonist potency by 1 week after clocinnamox. Etonitazene (0.0001-0.01 mg/kg) was also antagonized by clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The smaller extent of antagonism was not due to the appearance of non mu-opioid response-decreasing effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg) shifted the etonitazene dose-effect curve in the presence of clocinnamox (0.1 mg/kg). Clocinnamox (0.1-0.32 mg/kg) did not antagonize the rate-suppressing effects of the delta-agonist BW373U86 (0.0.01-1.0 mg/kg) or the kappa-agonist U69,593 (0.001-0.032 mg/kg). These results are consistent with previous in vivo and in vitro evidence that characterized clocinnamox as an insurmountable antagonist, with selectivity for mu- over kappa- and delta-receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cinnamates / pharmacology*
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Macaca mulatta
  • Male
  • Morphine Derivatives / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Opioid Peptides / antagonists & inhibitors*
  • Opioid Peptides / pharmacology
  • Receptors, Opioid, delta / agonists
  • Receptors, Opioid, mu / agonists
  • Receptors, sigma / agonists
  • Reinforcement Schedule

Substances

  • Cinnamates
  • Morphine Derivatives
  • Narcotic Antagonists
  • Opioid Peptides
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Receptors, sigma
  • clocinnamox