Doty P, Dykstra L A, Picker M J
Department of Psychology, University of North Carolina at Chapel Hill 27599-3270.
Drug Alcohol Depend. 1994 Apr;35(2):151-8. doi: 10.1016/0376-8716(94)90122-8.
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) substituted 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 substitute for the PCP stimulus, up to doses that substantially decreased rate of responding. However, both delta 9-THC and delta 8-THC partially attenuated the discriminative stimulus effects of the PCP training dose. Furthermore, a dose of 3.0 mg/kg delta 9-THC shifted the PCP dose-effect curve for discriminative stimulus effects to the right and shifted the PCP dose-effect curve for rate of responding to the left. The attenuation of the PCP stimulus by delta 9-THC lacked a strong dose-dependent relationship and was observed both at doses which did not alter rate of responding, as well as at doses which substantially decreased rate. In contrast to the effects observed with delta 9-THC and delta 8-THC, morphine, d-amphetamine and chlordiazepoxide failed to attenuate the discriminative stimulus effects of PCP, even at doses that markedly decreased rate of responding. The present findings suggest that delta 9-THC and delta 8-THC alter the discriminative stimulus effects of PCP in a pharmacologically specific manner.
训练大鼠区分1.75毫克/千克剂量的苯环己哌啶（PCP）和生理盐水。在替代试验中，PCP（0.3 - 10.0毫克/千克）和非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂MK-801（0.01 - 0.3毫克/千克）均以剂量依赖性方式替代PCP刺激。相比之下，Δ9-四氢大麻酚（Δ9-THC，0.1 - 5.6毫克/千克）和Δ8-四氢大麻酚（Δ8-THC，0.3 - 5.6毫克/千克）直至大幅降低反应率的剂量，都未能替代PCP刺激。然而，Δ9-THC和Δ8-THC均部分减弱了PCP训练剂量的辨别性刺激效应。此外，3.0毫克/千克剂量的Δ9-THC使PCP辨别性刺激效应的剂量-效应曲线向右移动，并使PCP反应率的剂量-效应曲线向左移动。Δ9-THC对PCP刺激的减弱缺乏强烈的剂量依赖性关系，在不改变反应率的剂量以及大幅降低反应率的剂量下均有观察到。与Δ9-THC和Δ8-THC所观察到的效应相反，吗啡、右旋苯丙胺和氯氮卓即使在显著降低反应率的剂量下，也未能减弱PCP的辨别性刺激效应。目前的研究结果表明，Δ9-THC和Δ8-THC以药理学特异性方式改变PCP的辨别性刺激效应。
