Comparative effects of tetrahydrocannabinol on psychostimulant-induced behaviors

The behavioral effects of delta-9-tetrahydrocannabinol (THC), one of the major psychoactive cannabinoids in marijuana, were tested in two models of psychostimulant-induced behaviors in rats (locomotor behavior and stereotyped gnawing) induced by amphetamine (AMPH) and methylphenidate (MEPH). Pretreatment with THC (10 mg/kg gavage) almost doubled the amount of AMPH-induced gnawing but produced no effect on AMPH-induced locomotor behavior. In contrast to AMPH, THC produced no direct effect on MEPH-induced gnawing but caused a strong suppression of MEPH-induced locomotor activity. In addition, there was no additional interaction between THC and reserpine as measured by suppression of MEPH-induced gnawing. This result was unexpected in view of the powerful interaction between THC and reserpine reported previously. Because of the clear THC-induced dissociation of the behavioral effects of these two psychostimulants (AMPH and MEPH), our working hypothesis is that THC affects motor behaviors by some non-dopaminergic mechanism.