SR 141716A differentially attenuates the behavioral effects of delta9-THC in rhesus monkeys.
Lance R Mcmahon, M R Amin, Charles P France
Behavioural Pharmacology September 2005 DOI: 10.1097/00008877-200509000-00008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Sample size | 7 |
| Population | Rhesus monkeys (4 in the multiple-schedule group, 3 in the drug-discrimination group) |
| Interventions | SR 141716A delta9-tetrahydrocannabinol (delta9-THC) |
| Dose | SR 141716A 0.32 mg/kg and 1.0 mg/kg; delta9-THC 0.1 mg/kg (i.v., discrimination), 0.32 mg/kg, 3.2 mg/kg |
| Topics | Cannabis |
| Key findings | SR 141716A (0.32 mg/kg) attenuated delta9-THC-induced hypothermia without attenuating delta9-THC's rate-decreasing effects in either component of a multiple schedule, and 1.0 mg/kg SR 141716A itself decreased rectal temperature and food-component responding. In monkeys discriminating delta9-THC, SR 141716A (0.32 and 1 mg/kg) increased the delta9-THC ED50 by 2.3- and 3.7-fold. The authors conclude that the behavioral effects of delta9-THC are not equally attenuated by SR 141716A. |
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 delta9-tetrahydrocannabinol (delta9-THC). This study examined the effects of SR 141716A on the rate-decreasing, hypothermic and discriminative stimulus effects of delta9-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. delta9-THC to decrease responding in the food component (ED50=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 delta9-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 degrees C at a dose of 3.2 mg/kg. A dose of 0.32 mg/kg of SR 141716A, significantly attenuated delta9-THC-induced hypothermia without attenuating the rate-decreasing effects of delta9-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. delta9-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 ED50 of the delta9-THC by 2.3- and 3.7-fold, respectively. Collectively, these results demonstrate that the behavioral effects of delta9-THC are not equally attenuated by SR 141716A.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 7
- Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospinal fluid. Journal of Pharmacology and Experimental Therapeutics February 1, 2009
- Clinical and Preclinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol. Neuropsychopharmacology January 2018
- Cannabinoid discrimination and antagonism by CB(1) neutral and inverse agonist antagonists. Journal of Pharmacology and Experimental Therapeutics March 2013
- Δ⁹Tetrahydrocannabinol impairs visuo-spatial associative learning and spatial working memory in rhesus macaques. Journal of Psychopharmacology October 2012
- Apparent affinity estimates of rimonabant in combination with anandamide and chemical analogs of anandamide in rhesus monkeys discriminating Delta9-tetrahydrocannabinol. Psychopharmacology April 2009
and 2 more in the library
Cites 2
- (R)-methanandamide and Delta 9-THC as discriminative stimuli in rats: tests with the cannabinoid antagonist SR-141716 and the endogenous ligand anandamide. Psychopharmacology August 2001
- Effects of the cannabinoid CB1 receptor antagonist SR141716A on the behavior of pigeons and rats. Psychopharmacology April 1996