DISCRIMINATIVE STIMULUS EFFECTS OF PHENCYCLIDINE - PHARMACOLOGICALLY SPECIFIC INTERACTIONS WITH DELTA(9)-TETRAHYDROCANNABINOL AND DELTA(8)-TETRAHYDROCANNABINOL

Rats were trained to discriminate a dose of 1.75 mg/kg phencyclidine ( PCP) from saline. During substitution tests, both PCP (0.3-10.0 mg/kg) and the non-competitive NMDA antagonist, MK-801 (0.01-0.3 mg/kg) subs tituted for the PCP stimulus in a dose-dependent manner. In contrast, Delta(9)-tetrahydrocannabinol (Delta(9)-THC, 0.1-5.6 mg/kg) and Delta( 8)-tetrahydrocannabinol (Delta(8)-THC, 0.3-5.6 mg/kg) failed to substi tute for the PCP stimulus, up to doses that substantially decreased ra te of responding. However, both Delta(9)-THC and Delta(8)-THC partiall y attenuated the discriminative stimulus effects of the PCP training d ose. Furthermore, a dose of 3.0 mg/kg Delta(9)-THC shifted the PCP dos e-effect curve for discriminative stimulus effects to the right and sh ifted the PCP dose-effect curve for rate of responding to the left. Th e attenuation of the PCP stimulus by Delta(9)-THC lacked a strong dose -dependent relationship and was observed both at doses which did not a lter rate of responding, as well as at doses which substantially decre ased rate. In contrast to the effects observed with Delta(9)-THC and D elta(8)-THC, morphine, d-amphetamine and chlordiazepoxide failed to at tenuate the discriminative stimulus effects of PCP, even at doses that markedly decreased rate of responding. The present findings suggest t hat Delta(9)-THC and Delta(8)-THC alter the discriminative stimulus ef fects of PCP in a pharmacologically specific manner.