Clocinnamox inhibits the intravenous self-administration of opioid agonists in rhesus monkeys: Comparison with effects on opioid agonist-mediated antinociception

G. Zernig, J. W. Lewis, J. H. Woods

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The effects of CCAM, an insurmountable mu opioid receptor antagonist, were studied on the intravenous self-administration and thermoantinociception of alfentanil and nalbuphine, high- and low-efficacy opioid agonists, respectively, in rhesus monkeys. A single dose of 0.1 mg/kg CCAM IV reduced alfentanil's reinforcing potency in an FR30 TO 45 s schedule 10-fold within a 24-h period. The maximum response rates remained essentially unchanged. At 1 mg/kg, CCAM caused a 300-fold shift of the alfentanil dose-response curve and also depressed the maximum response rates. CCAM also blocked insurmountably responding for nalbuphine, which was essentially abolished in two of three animals after a dose of 0.1 mg/kg CCAM and in all animals after 1 mg/kg. The acute insurmountable antagonism of alfentanil and nalbuphine self-administration by CCAM was used to determine the (relative initial) efficacy values of both agonists. Efficacy values, tau, were 391 for alfentanil and 196 for nalbuphine; the apparent in vivo dissociation constants, K(A), were 0.16 mg/kg per injection (i.e., 350 nmol/kg per injection) for alfentanil and 0.14 mg/kg (370 nmol/kg per injection) for nalbuphine. In comparison, in a rhesus monkey 50°C warm-water tail withdrawal assay, the tau values were 11 for alfentanil and 0.92 for nalbuphine, and the K(A) values were 0.2 mg/kg (440 nmol/kg) for alfentanil and 0.15 mg/kg (400 nmol/kg) for nalbuphine. Therefore, it seems that the higher potency of alfentanil and nalbuphine in self-administration as compared to thermal antinociception in rhesus monkeys is predominantly due to a larger efficacy of the same agonist in self-administration (i.e., a larger receptor pool) rather than differences in apparent in vivo affinity.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalPsychopharmacology
Volume129
Issue number3
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Alfentanil
  • Antinociception
  • Apparent in vivo affinity
  • Clocinnamox
  • Efficacy
  • Mu receptors
  • NIH 10443
  • Nalbuphine
  • Operant responding
  • Opioid receptors
  • Receptor reserve
  • Reinforcement
  • Self-administration
  • Spare receptors

ASJC Scopus subject areas

  • Pharmacology

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