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Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6J mice.
Eur J Pharmacol. 2009 Aug 01; 615(1-3):102-7.EJ

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.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, United States.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19470387

Citation

Vann, Robert E., et al. "Discriminative Stimulus Properties of Delta9-tetrahydrocannabinol (THC) in C57Bl/6J Mice." European Journal of Pharmacology, vol. 615, no. 1-3, 2009, pp. 102-7.
Vann RE, Warner JA, Bushell K, et al. Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6J mice. Eur J Pharmacol. 2009;615(1-3):102-7.
Vann, R. E., Warner, J. A., Bushell, K., Huffman, J. W., Martin, B. R., & Wiley, J. L. (2009). Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6J mice. European Journal of Pharmacology, 615(1-3), 102-7. https://doi.org/10.1016/j.ejphar.2009.05.010
Vann RE, et al. Discriminative Stimulus Properties of Delta9-tetrahydrocannabinol (THC) in C57Bl/6J Mice. Eur J Pharmacol. 2009 Aug 1;615(1-3):102-7. PubMed PMID: 19470387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6J mice. AU - Vann,Robert E, AU - Warner,Jonathan A, AU - Bushell,Kristen, AU - Huffman,John W, AU - Martin,Billy R, AU - Wiley,Jenny L, Y1 - 2009/05/23/ PY - 2008/12/01/received PY - 2009/05/05/revised PY - 2009/05/18/accepted PY - 2009/5/28/entrez PY - 2009/5/28/pubmed PY - 2009/11/11/medline SP - 102 EP - 7 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 615 IS - 1-3 N2 - 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. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19470387/Discriminative_stimulus_properties_of_delta9_tetrahydrocannabinol__THC__in_C57Bl/6J_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)00491-9 DB - PRIME DP - Unbound Medicine ER -