Modulatory effects of morphine, U-50488H and 1,3-di-(2-tolyl)guanidine on cocaine-like discriminative stimulus in the...

The present study was designed to investigate the effects of the mu-opioid morphine, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]-benzene acetamide, methane sulfonate hydrate (U-50488H), a kappa-selective opioid receptor agonist, and 1,3-di-(2-tolyl)guanidine (DTG), sigma-receptor agonist, on the discriminative stimulus properties of cocaine in the rat trained to discriminate 10 mg/kg of cocaine from its vehicle in a shock avoidance paradigm. Morphine (1-5.6 mg/kg), U-50488H (1-10 mg/kg) or 1,3-di-(2-tolyl) guanidine (1 and 10 mg/kg) alone did not produce any stimulus effects in common with cocaine. In contrast, morphine (5.6 mg/kg) and DTG (10 mg/kg), unlike U-50488H (10 mg/kg), significantly shifted the stimulus-generalization curve for cocaine to the left. These results suggest that agonists for mu-opioid- and sigma-receptors augment the discriminative stimulus properties of cocaine.