Interactions between the CB1 receptor agonist Delta 9-THC and the CB1 receptor antagonist SR-141716 in rats: open-field revisited.

This study examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and the CB1 antagonist SR-141716 on open-field behaviors in male Sprague-Dawley rats. Animals were examined after administration of Delta(9)-THC alone (dose range: 0.3-5.6 mg/kg), SR-141716 alone (dose range: 1-5.6 mg/kg) and the two drugs in combination; injections were given intraperitoneally 30 min prior to testing. There was a dose-related suppression of ambulation (horizontal activity) and rearing (vertical activity) after Delta(9)-THC administration. Co-administration of SR-141716 counteracted this suppression; however, antagonism was only partial for rearing. Interestingly, 1 mg/kg SR-141716 was as effective as 3 and 5.6 mg/kg SR-141716 in this antagonist action. Increasing doses of Delta(9)-THC produced an increase in circling behavior; latency to leave the starting area in the center of the field was significantly elevated by 5.6 mg/kg Delta(9)-THC. Those effects were completely blocked by SR-141716. Grooming and scratching showed a dose-related increase following administration of SR-141716 (1-5.6 mg/kg), which were only partially blocked by co-administration of Delta(9)-THC (3 and 5.6 mg/kg). When given alone, only the highest dose of SR-141716 (5.6 mg/kg) depressed ambulation; rearing and latency were not significantly changed, and circling was absent. Differences in the number of vocalizations, urination and defecation generally did not differ clearly among the treatment conditions. These results may show that SR-141716 is acting as (i) an inverse agonist and/or (ii) that the endogenous cannabinoid system is tonically active under certain conditions.