SR 141716A differentially attenuates the behavioral effects of Δ9-THC in rhesus monkeys

Lance R. McMahon, M. R. Amin, C. P. France

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The prototypic cannabinoid CB1 antagonist SR 141716A is one important pharmacologic tool for examining CB1 receptors that mediate the behavioral and physiologic effects of Δ9- tetrahydrocannabinol (Δ9-THC). This study examined the effects of SR141716A on the rate-decreasing, hypothermic and discriminative stimulus effects of Δ9-THC in rhesus monkeys. In monkeys (n=4) responding under a multiple fixed ratio (FR-10:FR-10) schedule of food presentation and stimulus-shock termination, the potency of i.m. Δ9-THC to decrease responding in the food component (ED 50=0.64 mg/kg) was threefold greater than its potency in the stimulus-shock termination component (ED50=2.14 mg/kg). In the same monkeys, hypothermia was induced by Δ9-THC at a dose (e.g. 0.32 mg/kg) that did not alter responding in either schedule component; the maximum decrease was 2.1°C at a dose of 3.2 mg/kg. A dose of 0.32 mg/kg of SR 141716A, significantly attenuated Δ9-THC-induced hypothermia without attenuating the rate-decreasing effects of Δ9-THC in either component of the multiple schedule. The largest dose of i.m. SR 141716A that was studied, 1.0 mg/kg, significantly decreased rectal temperature and responding in the food component but did not significantly decrease responding in the stimulus-shock termination component of the multiple schedule. In a separate group of monkeys (n=3) that discriminated i.v. Δ9-THC (0.1 mg/kg) while responding under an FR-5 schedule of stimulus-shock termination, SR 141716A (0.32 and 1 mg/kg) significantly increased the ED 50 of the Δ9-THC by 2.3- and 3.7-fold, respectively. Collectively, these results demonstrate that the behavioral effects of Δ9-THC are not equally attenuated by SR 141716A.

Original languageEnglish (US)
Pages (from-to)363-372
Number of pages10
JournalBehavioural pharmacology
Volume16
Issue number5-6
DOIs
StatePublished - Sep 2005

Keywords

  • Antagonist
  • Cannabinoid
  • Hypothermia
  • Rhesus monkey
  • SR 141716A
  • Schedule-controlled behavior
  • Δ-THC

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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