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Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol in C57BL/6J mice.
Psychopharmacology (Berl). 2008 Jul; 198(4):487-95.P

Abstract

RATIONALE

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.

OBJECTIVE

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

Links

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    ncbi.nlm.nih.gov
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    Authors+Show Affiliations

    McMahon LR
    Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. mcmahonl@uthscsa.edu.
    Ginsburg BC
    No affiliation info available
    Lamb RJ
    No affiliation info available

    MeSH

    AnimalsArachidonic AcidsBenzoxazinesCannabinoidsCyclohexanolsData Interpretation, StatisticalDiscrimination LearningDiscrimination, PsychologicalDose-Response Relationship, DrugDronabinolDrug InteractionsHallucinogensMaleMiceMice, Inbred C57BLMorpholinesNaphthalenesPiperidinesPyrazolesReceptor, Cannabinoid, CB1Reinforcement ScheduleRimonabant

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    17673980

    Citation

    McMahon, Lance R., et al. "Cannabinoid Agonists Differentially Substitute for the Discriminative Stimulus Effects of Delta(9)-tetrahydrocannabinol in C57BL/6J Mice." Psychopharmacology, vol. 198, no. 4, 2008, pp. 487-95.
    McMahon LR, Ginsburg BC, Lamb RJ. Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol in C57BL/6J mice. Psychopharmacology (Berl). 2008;198(4):487-95.
    McMahon, L. R., Ginsburg, B. C., & Lamb, R. J. (2008). Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol in C57BL/6J mice. Psychopharmacology, 198(4), 487-95.
    McMahon LR, Ginsburg BC, Lamb RJ. Cannabinoid Agonists Differentially Substitute for the Discriminative Stimulus Effects of Delta(9)-tetrahydrocannabinol in C57BL/6J Mice. Psychopharmacology (Berl). 2008;198(4):487-95. PubMed PMID: 17673980.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabinoid agonists differentially substitute for the discriminative stimulus effects of Delta(9)-tetrahydrocannabinol in C57BL/6J mice. AU - McMahon,Lance R, AU - Ginsburg,Brett C, AU - Lamb,R J, Y1 - 2007/08/03/ PY - 2007/06/06/received PY - 2007/07/11/accepted PY - 2007/8/4/pubmed PY - 2008/11/18/medline PY - 2007/8/4/entrez SP - 487 EP - 95 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 198 IS - 4 N2 - RATIONALE: 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. OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/17673980/Cannabinoid_agonists_differentially_substitute_for_the_discriminative_stimulus_effects_of_Delta_9__tetrahydrocannabinol_in_C57BL/6J_mice_ L2 - https://dx.doi.org/10.1007/s00213-007-0900-2 DB - PRIME DP - Unbound Medicine ER -