FAILURE OF DELTA(9)-TETRAHYDROCANNABINOL AND CP-55,940 TO MAINTAIN INTRAVENOUS SELF-ADMINISTRATION UNDER A FIXED-INTERVAL SCHEDULE IN RHESUS-MONKEYS

The lack of procedures which can unequivocally demonstrate cannabinoid self-administration in animals has been an obstacle to the study of the neural basis for the reinforcing effects of this drug class. Because Delta(9)-tetrahydrocannabinol (Delta(9)-THC) produces a relatively slow-onset, long-lasting behavioral effect, a self-administration procedure with widely spaced drug deliveries was evaluated as an alternative to fixed-ratio schedules which typically require frequent, closely spaced injections to demonstrate reinforcing effects. Three adult male rhesus monkeys were surgically implanted with intravenous catheters and trained to self-administer phencyclidine (PCP) under a 10 min fixed-interval schedule of reinforcement. Three injections were available each day, separated by 2 h periods during which responding had no programmed consequences. In an attempt to link the effect of the drug with the response which produced it, each 20 s injection was paired with a red light which remained illuminated for 10 min. PCP (100 mu g/kg/injection) maintained steady rates of responding during each availability period, ranging from approximately 0.2 to 0.7 responses/s. During 7 day substitution periods, Delta(9)-THC (17-100 mu g/kg/injection) maintained low rates of responding which occasionally surpassed those during vehicle substitutions, but fell far below rates maintained by PCP. Substitution tests with the potent Delta(9)-THC analog CP 55,940 also resulted in low rates of responding. These results demonstrate that Delta(9)-THC is a poor reinforcer in animals, even under conditions where some of its unfavourable biodispositional properties are taken into consideration.