Modulatory effects of morphine, U-50488H and 1,3-di-(2-tolyl)guanidine on cocaine-like discriminative stimulus in the rat using two-choice discrete-trial avoidance paradigm.
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.
Ukai
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Mori
E
E
Kameyama
T
T
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003042:Cocaine / Q000633:toxicity*; D004193:Discrimination Learning / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D018765:Dopamine Uptake Inhibitors; D006146:Guanidines; D011957:Receptors, Opioid; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D003042:Cocaine; C050232:1,3-ditolylguanidine