CB1 receptor mediation of cannabinoid behavioral effects in male and female rats

Rationale. Cannabinoids have been shown to produce greater behavioral effects in female than male rats. Although central nervous system CB1 receptors are known to mediate cannabinoid-induced behavioral effects in male rats, it is not known whether the same is true for females. Objective. To determine if cannabinoid-induced antinociception and catalepsy are similarly mediated by central CB1 receptors in male and female rats. Methods. The ability of SR141716A, a CB1 receptor selective antagonist, administered ICV (1-1000 mug) or IT (1-600 mug) to block 10 mg/kg IP Delta(9)-THC-induced antinociception (paw pressure) and catalepsy (bar test), was compared in male and female rats. Results. Delta(9)-THC alone produced slightly greater antinociception, and significantly greater catalepsy in females than males. When administered ICV, SR141716A partially antagonized Delta(9)-THC-induced antinociception in both females and males. IT SR141716A also antagonized Delta(9)-THC-induced antinociception in both sexes; it was slightly more potent in males but equally effective in males and females. SR141716A antagonized Delta(9)-THC-induced catalepsy in a similar manner in males and females when given ICV or IT. Conclusions. These results confirm that Delta(9)-THC-induced behavioral effects are mediated by central CB1 receptors in male and female rats.