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Spontaneous and rimonabant‐precipitated cannabinoid withdrawal in Δ9‐tetrahydrocannabinol and AM2389‐treated mice (838.5)
Author(s) -
Chopda Girish,
Nikas Spyros,
Shukla Vidyanand,
Makriyannis Alexandros,
Paronis Carol
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.838.5
Subject(s) - rimonabant , agonist , cannabinoid , cannabinoid receptor , antagonist , inverse agonist , pharmacology , tetrahydrocannabinol , withdrawal syndrome , medicine , anesthesia , receptor
Cannabinoid (CB) withdrawal following exposure to THC has been described for human and nonhuman primates. Yet, despite several reports of antagonist‐precipitated CB withdrawal, spontaneous CB withdrawal has not been characterized in mice. Experiments compared the effects of rimonabant or vehicle in mice injected daily with THC or AM2389 (high efficacy CB agonist) using two indices of drug effect: increased paw tremors and decreased operant responding. For paw tremor studies, mice received 10‐20 mg/kg/day THC or 0.03‐1.0 mg/kg/day AM2389 for 5‐28 days and effects of vehicle or 1‐10 mg/kg rimonabant on observable behaviors (e.g. paw tremors) were evaluated at 4‐48 hr after the last CB agonist injection. Other mice, trained to respond (nosepoke) for 0.02 ml of sweetened milk, received 0.1 mg/kg/day AM2389 and the effects of AM2389, rimonabant, or vehicle on response rate were recorded. Results show increased paw tremors following vehicle injection at 24hr after AM2389 whereas rimonabant increased paw tremors at 4‐24 hr after AM2389 or THC injection, with some evidence that contextual cues may influence the expression of withdrawal. Similarly, both rimonabant and interruption of the daily dosing regimen decreased operant responding in AM2389‐treated mice. These results indicate that daily treatment with a high efficacy CB agonist will result in dependence that can be measured via spontaneous withdrawal effects.