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 saline in a two-lever, food-reinforced, discrimination task. Neither fentanyl, 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, cocaine reversed the rate-suppressant effects of fentanyl. Although the kappa agonist U50,488H decreased response rates, it did not substitute for cocaine. Injection of U50,488H in combination with the training dose 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 and mu antagonists respectively, did not block the effects of cocaine. Further, naltrindole did not substitute for the cocaine cue. Complete generalization 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 the discriminative stimulus effects of cocaine. Moreover, activation of delta receptors and blockade of mu and delta receptors are similarly ineffective.
Broadbent
J
J
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157, USA.
Gaspard
T M
TM
Dworkin
S I
SI
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016642:Bupropion / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005283:Fentanyl / Q000494:pharmacology; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D012055:Reinforcement Schedule
D000700:Analgesics; D001549:Benzamides; D018847:Opioid Peptides; D010879:Piperazines; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D016642:Bupropion; C083877:BW 373U86; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C055382:naltrindole; D003042:Cocaine; D005283:Fentanyl