Tags

Type your tag names separated by a space and hit enter

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

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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info available

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), 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. 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 -