Journal
BEHAVIOURAL PHARMACOLOGY
Volume 23, Issue 8, Pages 802-805Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FBP.0b013e32835a7c4d
Keywords
AM2389; efficacy; mouse; partial agonist; Delta(9)-tetrahydrocannabinol
Funding
- National Institute of Health National Institute on Drug Abuse [DA23142]
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Delta(9)-Tetrahydrocannabinol (THC) has been characterized as a partial agonist at cannabinoid CB1 receptors in vitro; however, it often produces the same maximum effects in vivo as other cannabinoid agonists. This study was carried out to determine whether THC would antagonize the hypothermic effects of another cannabinoid agonist, AM2389, in mice. Male mice were injected with 1-100mg/kg THC, 0.01-0.1mg/kg AM2389, or a combination of 30mg/kg THC and 0.1-1.0mg/kg AM2389, and rectal temperature was recorded for up to 12 h after injection. THC reduced the temperature by 5.6 degrees C at a dose of 30mg/kg; further increases in the dose did not produce larger effects, indicating a plateau in the THC dose-effect function. AM2389 reduced temperature by 9.0 degrees C at a dose of 0.1mg/kg. One hour pretreatment with 30mg/kg THC attenuated the hypothermic effects of 0.1mg/kg AM2389; a 10-fold higher dose, 1.0mg/kg AM2389, was required to further decrease temperature, reflecting a five-fold rightward shift of the lower portion of the AM2389 dose-effect function following THC pretreatment. These results indicate that, in an assay of mouse hypothermia, THC exerts both agonist and antagonist effects following acute administration, and mark the first demonstration of partial agonist/antagonist effects of THC in vivo. Behavioural Pharmacology 23: 802-805 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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