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Apparent p A 2 analysis of cannabinoid antagonists in monkeys discriminating Δ 9 ‐tetrahydrocannabinol (Δ 9 ‐THC)
Author(s) -
McMahon Lance Richard
Publication year - 2006
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.20.4.a682
Subject(s) - cannabinoid , cannabinoid receptor , schild regression , cannabinoid receptor agonists , chemistry , pharmacology , tetrahydrocannabinol , receptor , cannabinol , agonist , biology , biochemistry
The behavioral effects of cannabis are presumably mediated by actions of Δ 9 ‐THC at cannabinoid CB 1 receptors, and the behavioral effects of other cannabinoid agonists also are presumably mediated by CB 1 receptors. Schild analysis was used to examine whether interactions between cannabinoid antagonists and agonists were consistent with a simple, competitive interaction at CB 1 receptors in rhesus monkeys discriminating Δ 9 ‐THC (0.1 mg/kg, i.v.). In addition to Δ 9 ‐THC, the cannabinoid agonists CP 55940 and WIN 55212‐2 occasioned high levels of responding (i.e. greater than 90%) on the Δ 9 ‐THC lever, whereas the CB 1 antagonists SR 141716A and AM 251 did not. Rather, SR 141716A (0.32–3.2 mg/kg) surmountably antagonized Δ 9 ‐THC, CP 55940 and WIN 55212‐2 and Schild analysis was consistent with a simple, competitive interaction (i.e. slope of the Schild plot was not different from unity); p A 2 values (6.21, 6.47, and 6.66 determined with Δ 9 ‐THC, CP 55940 and WIN 55212‐2, respectively) were not significantly different. Similar antagonism of Δ 9 ‐THC and WIN 55212‐2 was obtained with AM 251 (0.32–3.2 mg/kg); Schild analysis was consistent with a simple, competitive interaction and p A 2 values (6.27 and 6.58 determined with Δ 9 ‐THC and WIN 55212‐2, respectively) were not significantly different. These results indicate that the discriminative stimulus effects of Δ 9 ‐THC, CP 55940 and WIN 55212‐2 are mediated by CB 1 receptors, and demonstrate the utility of Schild analysis for examining CB 1 receptors that mediate the behavioral effects of cannabinoid agonists. Supported by USPHS grants DA15468 and DA19222