Modulation of the discriminative stimulus effects of d-amphetamine by mu and kappa opioids in squirrel monkeys

It has been reported that the discriminative stimulus effects of cocaine in squirrel monkeys can be potentiated by mu opioid agonists and attenuated by kappa opioid agonists. The purpose of this study was to extend these observations by examining the effects of mu and kappa opioids agonists on the discriminative stimulus effects of d-amphetamine (AMPH). Five squirrel monkeys were trained to discriminate 0.3 mg/kg of AMPH (i.m.) from saline using a stimulus termination/avoidance task. AMPH and cocaine substituted dose dependently for the AMPH training stimulus in all five monkeys. The AMPH training dose was completely antagonized by 0.1 mg/kg of the D1 dopamine antagonist SCH 39166. When administered alone, the kappa agonist U69,593 substituted partially or completely for AMPH in four of five monkeys, the kappa agonist enadoline substituted completely for AMPH in two of five monkeys, and morphine substituted completely for AMPH in one monkey. In all five monkeys, pretreatment with some doses of U69,593 or enadoline attenuated the discriminative stimulus effects of AMPH; however, some doses of U69,593 and enadoline also potentiated the effects of AMPH in at least two monkeys. Morphine pretreatment potentiated the discriminative stimulus effects of AMPH in three monkeys and either attenuated or did not alter these effects in two monkeys. Morphine pretreatment did not significantly alter the discriminative stimulus effects of cocaine except in one monkey. These data indicate large individual differences in the abilities of mu and kappa opioid agonists to alter the discriminative stimulus effects of AMPH.