Interaction between discriminative stimulus effects of cocaine and morphine.

We recently demonstrated that combining cocaine and morphine could enhance their reinforcing effects which may be mediated by the dopaminergic system. In the present study, the effects of cocaine and morphine on the discriminative stimulus effects of morphine and cocaine, respectively, were examined. Furthermore, dopaminergic mediation in the discriminative stimulus effects of morphine was also examined. Pretreatment with 1.0 or 3.0 mg/kg morphine shifted the dose-response curve for cocaine to the left, and 3.0 mg/kg morphine significantly potentiated the discriminative stimulus effects of cocaine. On the other hand, neither 1.25 nor 2.5 mg/kg cocaine affected the discriminative stimulus effects of morphine. These results suggest that potentiation of the discriminative stimulus effects of cocaine by morphine may reflect the enhancement of reinforcing effects in the combination of cocaine and morphine. Furthermore, neither SCH23390 (D1-receptor antagonist) nor haloperidol (D2-receptor antagonist) affects the discriminative stimulus effects of morphine, while combining these drugs slightly attenuated the effects of morphine. Thus, another neurotransmitter rather than dopamine may play an important role in the discriminative stimulus effects of morphine. Therefore, the discriminative stimulus effects of morphine are apparently not potentiated by cocaine, unlike those of reinforcing effects.