Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol in C57BL/6J mice.
Lance R Mcmahon, Brett C Ginsburg, R J Lamb
Psychopharmacology July 2008 DOI: 10.1007/s00213-007-0900-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Sample size | 8 |
| Population | C57BL/6J mice |
| Interventions | Delta(9)-THC CP 55940 WIN 55212-2 methanandamide cocaine ethanol ketamine SR 141716A (rimonabant) |
| Dose | Delta(9)-THC 10 mg/kg i.p. |
| Topics | Cannabis |
| Key findings | Delta(9)-THC can serve as a discriminative stimulus in mice, with dose-dependent effects (ED50 = 2.6 mg/kg). CP 55940 and WIN 55212-2 fully substituted for Delta(9)-THC, whereas methanandamide and noncannabinoids produced limited substitution. The CB1 antagonist rimonabant blocked Delta(9)-THC, CP 55940, and WIN 55212-2 effects, but not methanandamide, indicating that methanandamide's effects are mediated at least partly by non-CB1 receptors. |
Abstract
A variety of behavioral procedures have been developed to assess cannabinoid activity in mice; however, the feasibility of establishing Delta(9)-THC as a discriminative stimulus in mice has not been documented. One goal was to establish Delta(9)-THC as a discriminative stimulus in mice; after having done so, another goal was to examine the in vivo mechanism of action of Delta(9)-THC with other cannabinoids and noncannabinoids. C57BL/6J mice (n = 8) were trained to discriminate Delta(9)-THC (10 mg/kg i.p.) from vehicle while responding under a fixed ratio 30 schedule of food presentation. Mice satisfied the discrimination criteria in 18-98 (median = 67) sessions and the discriminative stimulus effects of Delta(9)-THC were dose-dependent (ED(50) = 2.6 mg/kg). CP 55940 and WIN 55212-2 dose-dependently increased Delta(9)-THC-appropriate responding to 100% (ED(50) = 0.032 and 0.45 mg/kg, respectively), whereas methanandamide and a variety of noncannabinoids (cocaine, ethanol, and ketamine) produced a maximum of 34% Delta(9)-THC-appropriate responding. The cannabinoid CB(1) antagonist SR 141716A (rimonabant) surmountably antagonized the discriminative effects of Delta(9)-THC, CP 55940, and WIN 55212-2; methanandamide did not significantly modify the Delta(9)-THC discriminative stimulus. The discriminative stimulus effects of Delta(9)-THC, CP 55940, and WIN 55212-2 are mediated by the same (i.e., CB(1)) receptors, whereas the effects of methanandamide or a metabolite of methanandamide are mediated at least in part by non-CB(1) receptors. The discriminative stimulus effects of Delta(9)-THC in mice could be used to evaluate mechanisms of cannabinoid activity with approaches (e.g., inducible knockouts) currently unavailable in nonmurine species.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Finding order in chemical chaos - Continuing characterization of synthetic cannabinoid receptor agonists. Neuropharmacology May 15, 2018
- Discriminative Stimulus Properties of Phytocannabinoids, Endocannabinoids, and Synthetic Cannabinoids. Current Topics in Behavioral Neurosciences 2018
- Phenotypic assessment of THC discriminative stimulus properties in fatty acid amide hydrolase knockout and wildtype mice. Neuropharmacology June 2015
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Cites 8
- The endogenous cannabinoid anandamide produces delta-9-tetrahydrocannabinol-like discriminative and neurochemical effects that are enhanced by inhibition of fatty acid amide hydrolase but not by inhibition of anandamide transport. Journal of Pharmacology and Experimental Therapeutics April 2007
- (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
- Cannabis: discrimination of "internal bliss"? Pharmacology, Biochemistry, and Behavior October 1999
- Delta9-THC training dose as a determinant for (R)-methanandamide generalization in rats. Psychopharmacology December 1998
- Evaluation of cannabimimetic effects of structural analogs of anandamide in rats. European Journal of Pharmacology August 21, 1998
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