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CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9-tetrahydrocannabinol.
J Pharmacol Exp Ther 1998; 285(3):1150-6JP

Abstract

Although tolerance to cannabinoids has been well established, the question of cannabinoid dependence had been very controversial until the discovery of a cannabinoid antagonist, SR141716A. The objective of this study was to develop and characterize a mouse model of precipitated withdrawal indicative of cannabinoid dependence. Using a dosing regimen known to produce pharmacological and behavioral tolerance, mice were treated with Delta9-tetrahydrocannabinol (Delta9-THC) twice a day for 1 wk. SR141716A administration after the last Delta9-THC injection promptly precipitated a profound withdrawal syndrome. Typical withdrawal behavior was an increase in paw tremors and head shakes that was accompanied with a decrease in normal behavior such as grooming and scratching. Of the three Delta9-THC regimens tested, daily Delta9-THC injections of 10 and 30 mg/kg produced the greatest number of paw tremors and head shakes and the least number of grooms after challenge with SR141716A. Precipitated withdrawal was apparent after 2, 3, 7 and 14 days of treatment based on an increase in paw tremors in Delta9-THC-treated mice as compared with vehicle-treated mice. These findings are consistent with SR141716A-precipitated withdrawal in rats. Moreover, these results suggest that mice are a viable model for investigating dependence to cannabinoids.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9618417

Citation

Cook, S A., et al. "CB1 Receptor Antagonist Precipitates Withdrawal in Mice Exposed to Delta9-tetrahydrocannabinol." The Journal of Pharmacology and Experimental Therapeutics, vol. 285, no. 3, 1998, pp. 1150-6.
Cook SA, Lowe JA, Martin BR. CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9-tetrahydrocannabinol. J Pharmacol Exp Ther. 1998;285(3):1150-6.
Cook, S. A., Lowe, J. A., & Martin, B. R. (1998). CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9-tetrahydrocannabinol. The Journal of Pharmacology and Experimental Therapeutics, 285(3), pp. 1150-6.
Cook SA, Lowe JA, Martin BR. CB1 Receptor Antagonist Precipitates Withdrawal in Mice Exposed to Delta9-tetrahydrocannabinol. J Pharmacol Exp Ther. 1998;285(3):1150-6. PubMed PMID: 9618417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB1 receptor antagonist precipitates withdrawal in mice exposed to Delta9-tetrahydrocannabinol. AU - Cook,S A, AU - Lowe,J A, AU - Martin,B R, PY - 1998/6/17/pubmed PY - 1998/6/17/medline PY - 1998/6/17/entrez SP - 1150 EP - 6 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 285 IS - 3 N2 - Although tolerance to cannabinoids has been well established, the question of cannabinoid dependence had been very controversial until the discovery of a cannabinoid antagonist, SR141716A. The objective of this study was to develop and characterize a mouse model of precipitated withdrawal indicative of cannabinoid dependence. Using a dosing regimen known to produce pharmacological and behavioral tolerance, mice were treated with Delta9-tetrahydrocannabinol (Delta9-THC) twice a day for 1 wk. SR141716A administration after the last Delta9-THC injection promptly precipitated a profound withdrawal syndrome. Typical withdrawal behavior was an increase in paw tremors and head shakes that was accompanied with a decrease in normal behavior such as grooming and scratching. Of the three Delta9-THC regimens tested, daily Delta9-THC injections of 10 and 30 mg/kg produced the greatest number of paw tremors and head shakes and the least number of grooms after challenge with SR141716A. Precipitated withdrawal was apparent after 2, 3, 7 and 14 days of treatment based on an increase in paw tremors in Delta9-THC-treated mice as compared with vehicle-treated mice. These findings are consistent with SR141716A-precipitated withdrawal in rats. Moreover, these results suggest that mice are a viable model for investigating dependence to cannabinoids. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9618417/CB1_receptor_antagonist_precipitates_withdrawal_in_mice_exposed_to_Delta9_tetrahydrocannabinol_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9618417 DB - PRIME DP - Unbound Medicine ER -