Abstract
The behavioral effects of cannabis are presumably mediated by actions of Δ9-THC at cannabinoid CB1 receptors, and the behavioral effects of other cannabinoid agonists also are presumably mediated by CB1 receptors. Schild analysis was used to examine whether interactions between cannabinoid antagonists and agonists were consistent with a simple, competitive interaction at CB1 receptors in rhesus monkeys discriminating Δ9-THC (0.1 mg/kg, i.v.). In addition to Δ9-THC, the cannabinoid agonists CP 55940 and WIN 55212-2 occasioned high levels of responding (i.e. greater than 90%) on the Δ9-THC lever, whereas the CB1 antagonists SR 141716A and AM 251 did not. Rather, SR 141716A (0.32–3.2 mg/kg) surmountably antagonized Δ9-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); pA2 values (6.21, 6.47, and 6.66 determined with Δ9-THC, CP 55940 and WIN 55212-2, respectively) were not significantly different. Similar antagonism of Δ9-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 pA2 values (6.27 and 6.58 determined with Δ9-THC and WIN 55212-2, respectively) were not significantly different. These results indicate that the discriminative stimulus effects of Δ9-THC, CP 55940 and WIN 55212-2 are mediated by CB1 receptors, and demonstrate the utility of Schild analysis for examining CB1 receptors that mediate the behavioral effects of cannabinoid agonists. Supported by USPHS grants DA15468 and DA19222
Published Version
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