Discriminative Stimulus Effects of Cp-55,940 and Structurally Dissimilar Cannabinoids in Rats

Abstract

CP 55,940 is a potent synthetic bicyclic cannabinoid analog that has been used in a number of studies as a radioligand for the cannabinoid receptor. This compound shares behavioral and biochemical properties with naturally occurring cannabinoids such as Delta(9)-THC. The purpose of the present study was 3-fold: to establish the ability of CP 55,940 to serve as a discriminative stimulus, to determine whether this discriminative stimulus is identical to that of Delta(9)-THC, and to examine whether a newly developed cannabinoid antagonist, SR141716A, would antagonize the discriminative stimulus effects of CP 55,940. Rats were trained to discriminate 0.1 mg/kg CP 55,940 from vehicle in standard 2-lever operant conditioning chambers. CP 55,940 produced dose-dependent generalization from the training dose in dose-effect determinations conducted before and after testing with other drugs. The effects of the training dose of CP 55,940 were dose-dependently antagonized by co-administration of SR141716A. Results of substitution tests showed that Delta(9)-THC, WIN 55,212-2, and cannabinol substituted completely for CP 55,940 in a dose-dependent manner; however, CP 55,940 was approx 10-fold more potent than any of the other drugs in producing CP 55,940-like discriminative stimulus effects. Several drugs with CNS depressant properties (phencyclidine, haloperidol and diazepam) failed to produce reliable substitution for CP 55,940. These results demonstrate that CP 55,940 has discriminative stimulus effects and that it shares these effects with structurally dissimilar compounds that, like CP 55,940, bind to the cannabinoid receptor. Further, these effects are blocked by SR141716A, a cannabinoid receptor antagonist. The present results provide support for the use of CP 55,940 as a probe for cannabinoid receptor-mediated effects related to cannabis abuse