Generalization of the discriminative stimulus properties of delta 9-THC to delta 9(11)-THC in rats.

Rats were trained in a water maze to discriminate between IP injections of 3 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) and its vehicle. Both delta 8- and delta 9(11)-THC were generalized to the training drug. In contrast to our observations in rhesus monkeys, where delta 9(11)-THC is at least 100 times less potent than delta 9-THC, delta 9(11)-THC was found to be only seven times less potent in the rat. Relative potencies, expressed as the dosage at which 50% of the animals gave drug responses (ED50) were 1.8 mg/kg and 12.2 mg/kg for delta 9- and delta 9(11)-THC respectively. Twenty-four hours after receiving 7 X ED50 = 12 mg/kg delta 9-THC the tests showed intermediate results when conducted with the training dosage; 4 X ED50 = 50 mg/kg delta 9(11)-THC 48 h prior to the training dosage of 3 mg/kg delta 9-THC completely blocked drug-appropriate responses. Coinjection of ED50 dosages of delta 9- and delta 9(11)-THC led to 90% drug responses, demonstrating the additivity of the cannabis-like effect of both cannabinoids. Differences in the individual sensitivity of the rats to the tested cannabinoids were observed. Findings are interpreted in terms of the receptor mechanism for cannabis-like activity.