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Vol. 285, Issue 3, 1150-1156, June 1998
9-Tetrahydrocannabinol1
Department of Pharmacology and Toxicology, Medical College of
Virginia, Virginia Commonwealth University, Richmond, Virginia and
Pfizer Central Research, Pfizer Inc., Groton, Connecticut
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 
9-tetrahydrocannabinol
(9-THC) twice a day for 1 wk. SR141716A administration
after the last 9-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 9-THC regimens tested, daily 9-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
9-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.
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