Fig. 2:

Effects of Xie2-64 on cocaine self-administration. A, Xie2-64, at the doses of 10 or 20 mg/kg, i.p., failed to alter cocaine self-administration maintained by 1 mg/kg/infusion under a low fixed-ratio (FR2) reinforcement schedule. B, Xie2-64 decreased cocaine self-administration in rats under a PR schedule of reinforcement. C, Xie2-64 reduced PR breakpoints for cocaine self-administration, indicating a reduction in motivation to earn cocaine reward. D, Xie2-64, at the same doses, inhibited cocaine self-administration maintained by lower doses of cocaine under an FR2 schedule of reinforcement and shifted the cocaine dose-response curves downward. E, SR144528, another CB₂R inverse agonist, also inhibited cocaine self-administration and shifted the cocaine dose-response curves downward. F, Xie2-64 reduced cocaine self-administration in wild-type, but not CB₂-KO mice, under a FR1 schedule of reinforcement. **p < 0.01, *p < 0.05 compared to vehicle treatment.