Similar enhancement of the discriminative stimulus effects of cocaine and GBR 12909 by heroin in squirrel monkeys

Rationale and objectives: Heroin previously was shown to engender partial cocaine-like discriminative stimulus (DS) effects in squirrel monkeys. The present study assessed the degree to which heroin modified the DS effects of cocaine and the cocaine-like DS effects of the selective dopamine transport blocker GBR 12909. Methods and results: In squirrel monkeys discriminating cocaine (0.3 mg/kg) from saline, cocaine and GBR 12909 dose-dependently engendered levels of responding on the cocaine-associated lever greater than or equal to 90% (full substitution). Heroin engendered full substitution for cocaine in two monkeys, partial substitution (75%) in a third monkey, and no substitution in the fourth monkey. When administered as a pretreatment, heroin shifted the dose-response function for cocaine to the left in the three monkeys for which heroin engendered cocaine-lever responding, but did not alter the DS effects of cocaine in the fourth monkey. Heroin pretreatment also shifted the dose-response function for the cocaine-like DS effects of GBR 12909 to the left in the former three monkeys, and did not alter the effects of GBR 12909 in the fourth monkey. Isobolographic analysis of the DS effects of cocaine-heroin and GBR 12909-heroin combinations in the former three monkeys revealed that the potencies of the combinations were not different from predicted values based on dose-additive effects. Conclusions: These findings show that heroin can enhance similarly the DS effects of cocaine and GBR 12909, suggesting that activation of dopaminergic systems underlies enhancement of the interoceptive effects of cocaine by heroin.