Discriminative stimulus effects of morphine in squirrel monkeys: Stimulants, opioids, and stimulant-opioid combinations

Morphine and other mu opioids mimic and/or modulate the discriminative stim ulus (DS) effects of cocaine, possibly reflecting mutual stimulation of mes olimbic dopamine activity. Less is known about the capacity of cocaine and related stimulants to modulate the DS effects of morphine. The present stud y investigated the effects of cocaine, amphetamine, and reference drugs, ad ministered alone and with morphine, in squirrel monkeys trained to discrimi nate morphine from vehicle. Additional studies determined the ability of op ioid and dopamine receptor antagonists to attenuate the DS effects of morph ine and the morphine-like effects of other drugs. The DS effects of morphin e were mimicked by the mu-opioid agonist fentanyl but not the delta-opioid agonists SNC 80 and BW 373U86 or the kappa-opioid agonist U50,488H, and wer e antagonized by the opioid antagonist naltrexone but not the dopamine anta gonist flupenthixol. In three of five monkeys, the DS effects of morphine a lso were mimicked by cocaine, amphetamine, and the dopamine transport inhib itor GBR 12909 but not the norepinephrine transport inhibitor talsupram or the serotonin transport inhibitor fluoxetine, and were antagonized by flupe nthixol but not naltrexone. In this subgroup, pretreatment with cocaine or amphetamine enhanced the DS effects of morphine, whereas in the other two m onkeys pretreatment with either stimulant attenuated the DS effects of morp hine. The results demonstrated Individual differences in morphine-like DS e ffects of stimulants that are mirrored by individual differences in their i nteractions with morphine. Furthermore, different mechanisms appear to medi ate the DS effects of morphine and the morphine-like DS effects of cocaine and amphetamine.