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Discriminative stimulus effects of the synthetic cannabinoid JWH‐018 in rhesus monkeys
Author(s) -
Rodriguez Jesse S,
McMahon Lance R
Publication year - 2013
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.27.1_supplement.1097.6
Subject(s) - stimulus control , cannabinoid , pharmacology , agonist , ed50 , rimonabant , potency , chemistry , receptor , cannabinoid receptor , medicine , in vitro , biochemistry , nicotine
JWH‐018 produces greater maximal stimulation of G‐proteins at cannabinoid CB1 receptors than Δ9‐tetrahydrocannabinol (Δ9‐ THC); whether this results in a difference in maximum behavioral effects is not clear. The aim of this study was to establish a behavioral assay requiring high agonist efficacy by training a relatively large dose (0.1 mg/kg i.v.) of JWH‐018 as a discriminative stimulus in rhesus monkeys (n=5). The potency (ED50 value) of JWH‐018 to produce discriminative stimulus effects and to decrease response rate was 0.01 mg/kg and 0.06 mg/kg, respectively. Other cannabinoids substituted for the JWH‐ 018 discriminative stimulus with the following rank order potency (ED50 in mg/kg): CP‐55940 (0.005) = JWH‐018 >; Δ9‐THC (0.04) = WIN‐55212–2 (0.04) = JWH‐073 (0.07). The CB1 receptor‐selective antagonist rimonabant surmountably antagonized the discriminative stimulus effects of JWH‐018 and Δ9‐THC; Schild and single‐dose apparent affinity analyses yielded pA2 and pKB values that were not significantly different from each other. These data strongly suggest that the same receptor type mediates the discriminative effects of JWH‐018 and Δ9‐THC. However, the reported difference in efficacy at this receptor type does not result in different levels of discriminative stimulus effect in a situation where such a difference is expected.