Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6J mice.
Robert E Vann, Jonathan A Warner, Kristen Bushell, John W Huffman, Billy R Martin, Jenny L Wiley
European Journal of Pharmacology August 1, 2009 DOI: 10.1016/j.ejphar.2009.05.010 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Male C57BL/6J mice |
| Interventions | Cannabinoid indoles Anandamide Phenylmethylsulphonyl fluoride Nicotine Rimonabant |
| Dose | 10 mg/kg THC |
| Topics | Cannabis |
| Key findings | THC served as an effective discriminative stimulus in mice, with dose-dependent self-substitution. Cannabinoid indoles substituted except one with low CB(1) affinity; anandamide substituted only when combined with the FAAH inhibitor phenylmethylsulphonyl fluoride; nicotine did not substitute; and the CB(1) antagonist rimonabant blocked THC's effects, demonstrating pharmacological specificity and CB(1) receptor involvement. |
Abstract
Primarily, rats have served as subjects in Delta(9)-tetrahydrocannabinol's (THC) discrimination studies although other species such as monkeys and pigeons have been used. While the introduction of the knockout and transgenic mice has vastly stimulated the study of the discriminative stimulus effects of drugs there is only a single published report of mice trained to discriminate THC. Thus, this study extended those results by providing a systematic replication that THC serves as an effective discriminative stimulus in mice and by further investigating the mechanisms of action involved in the THC discrimination model in the mouse. Male C57BL/6J mice were trained to discriminate 10 mg/kg THC from vehicle in 2-lever drug discrimination. THC fully and dose dependently substituted for itself. Cannabinoid indoles, except one with low cannabinoid CB(1) receptor affinity, substituted for THC. Anandamide failed to substitute for THC when administered alone but completely substituted when administered with the non-specific fatty acid amide hydrolase inhibitor, phenylmethylsulphonyl fluoride. As expected, nicotine failed to substitute for THC. Lastly, the cannabinoid CB(1) receptor antagonist rimonabant blocked THC's discriminative stimulus effects. Taken together these studies demonstrate THC's ability to produce discriminative stimulus effects as well as demonstrate its pharmacological specificity and mechanism of action in a two-lever drug discrimination mouse model.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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- Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents. Psychopharmacology June 1, 2010
- Discriminative stimulus properties of 3-substituent rimonabant analogs VCU Scholars Compass 2011
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and 13 more in the library
Cites 18
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- Apparent affinity estimates of rimonabant in combination with anandamide and chemical analogs of anandamide in rhesus monkeys discriminating Delta9-tetrahydrocannabinol. Psychopharmacology April 2009
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- Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol in C57BL/6J mice. Psychopharmacology July 2008
- 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
and 13 more in the library