TY - JOUR T1 - CB1 Receptor Antagonist Precipitates Withdrawal in Mice Exposed to Δ<sup>9</sup>-Tetrahydrocannabinol JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1150 LP - 1156 VL - 285 IS - 3 AU - Stacie A. Cook AU - John A. Lowe AU - Billy R. Martin Y1 - 1998/06/01 UR - http://jpet.aspetjournals.org/content/285/3/1150.abstract 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 Δ9-tetrahydrocannabinol (Δ9-THC) twice a day for 1 wk. SR141716A administration after the last Δ9-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 Δ9-THC regimens tested, daily Δ9-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 Δ9-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. The American Society for Pharmacology and Experimental Therapeutics ER -