Characteristics of tetrahydrocannabinol (THC)-produced discrimination in rats

Abstract

Rats were trained in a T-shaped maze to discriminate the effects produced by i.p. injections of tetrahydrocannabinol (THC) and the no-drug state (state-dependency, StD). Several doses of both Delta8-THC (range: 0.75-5.0 mg/kg) and Delta9-THC (range: 0.75-40.0 mg/kg) were used in order to compare the number of sessions required by the animals until reaching criterion performance. An additional group of rats had to discriminate pentobarbital sodium (20.0 mg/kg) from the no-drug state.

Results: THC discrimination was proportional to dose i.e., animals that had to differentiate high doses of THC from no drug acquired the T-maze task faster than animals trained with the lower doses of THC. Acquisition data further suggest that Delta8-THC is somewhat less potent than the Delta9-isomer. Delta9-THC (10.0 mg/kg) produces strong StD, as defined by Overton (1971), since both this group and the barbiturate group reached the criterion within the first 10 training sessions. Time and dose testings suggest that stimulus properties of drugs vary in a quantitative way and that the calculated ED50 values are mainly determined by the training dose used. It was found that the higher the training dose used the higher was the corresponding ED50 value. Hashish smoke can maintain drug responding among THC-trained rats. A lowered content of brain catecholamines and/or serotonin, induced by AMPT (150 mg/kg) and PCPA (310-350 mg/kg), did not lessen Delta9-THC (2.5 mg/kg) discrimination.