ASSESSMENT OF THE DISCRIMINATIVE STIMULUS EFFECTS OF COCAINE IN THE RAT - LACK OF INTERACTION WITH OPIOIDS

The present study examined the effects of several opioid agonists and antagonists in rats trained to discriminate cocaine (10 mg/kg) from sa line in a two-lever, food-reinforced, discrimination task. Neither fen tanyl, a mu agonist, nor the delta agonist BW 373U86 elicited cocaine- appropriate responding. Although pretreatment with fentanyl failed to alter the discriminative stimulus effects of low doses of cocaine, coc aine reversed the rate-suppressant effects of fentanyl. Although the k appa agonist U50,488H decreased response rates, it did not substitute for cocaine. Injection of U50,488H in combination with the training do se of cocaine (10 mg/kg) reversed the rate-suppressant effects of U50, 488H but failed to affect the cocaine cue. Administration of U50,488H (3 mg/kg), in conjunction with several doses of cocaine, did not shift the cocaine dose-response curve. Naltrindole and naltrexone, delta an d mu antagonists respectively, did not block the effects of cocaine. F urther, naltrindole did not substitute for the cocaine cue. Complete g eneralization was observed to the dopamine uptake inhibitor bupropion (30 mg/kg). These results suggest that fentanyl and U50,488H, at doses that purportedly influence mesolimbic dopamine levels, do not alter t he discriminative stimulus effects of cocaine. Moreover, activation of delta receptors and blockade of mu and delta receptors are similarly ineffective.