caa a22 4500 469121130 CHVBK 20180323133139.0 cr unu---uuuuu 170328e19920101xx s 000 0 eng 10.1007/BF02253585 doi (NATIONALLICENCE)springer-10.1007/BF02253585 Analgesic and discriminative stimulus properties of U-62,066E, the selective kappa-opioid receptor agonist, in the rat [Elektronische Daten] [Masuo Ohno, Tsuneyuki Yamamoto, Showa Ueki] The analgesic and discriminative stimulus properties of U-62,066E, a selective kappa-opioid receptor agonist, were investigated in the rat and compared with those of morphine. In the hot-plate test, U-62,066E produced a potent analgesic effect almost comparable to that of morphine. U-62,066E-induced analgesia was far less sensitive to antagonism by naloxone than was morphine-induced analgesia, but was potently reversed by MR-2266, a kappa-receptor antagonist. Although tolerance occurred to both U-62,066E and morphine analgesia, there was no cross-tolerance between these drugs. U-62,066E did show cross-tolerance to U-50,488H, another selective kappa-receptor agonist. Rats were trained to discriminate either 1.0 mg/kg U-62,066E or 3.2 mg/kg morphine from saline in a two-lever food-reinforced procedure. The stimulus effect of U-62,066E was substituted for by U-50,488H and E-2078 a stable dynorphin derivative, but not by morphine. None of the kappa-agonists substituted for the morphine stimulus. Although U-62,066E stimulus by itself was not antagonized by MR-2266 or naloxone up to as high a dose as 10 mg/kg, the U-62,066E-like stimulus effect of U-50,488H was markedly blocked by MR-2266. The dopamine antagonists haloperidol and sulpiride substituted for the U-62,066E stimulus cue that was, however, not attenuated by the dopamine agonist lisuride. Lisuride reversed the U-62,066E-like stimulus induced by U-50,488H. These findings indicate that U-62,066E has a potent analgesic effect that is mediated predominantly by kappa-opioid receptors, and that U-62,066E stimulus is, in contrast to its analgesic effect, based not only on the compound's kappa-agonist action and consequent inhibition of dopaminergic activity but also on the non-opioid mechanisms. Springer-Verlag, 1992 Kappa-opioid agonist nationallicence U-62,066E nationallicence Morphine nationallicence Analgesia nationallicence Drug discrimination nationallicence Rat nationallicence Ohno Masuo Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, 812, Fukuoka, Japan aut Yamamoto Tsuneyuki Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, 812, Fukuoka, Japan aut Ueki Showa Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, 812, Fukuoka, Japan aut Psychopharmacology Springer-Verlag 106/1(1992-01-01), 31-38 0033-3158 106:1<31 1992 106 213 https://doi.org/10.1007/BF02253585 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02253585 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ohno Masuo Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, 812, Fukuoka, Japan aut NATIONALLICENCE 700 1- Yamamoto Tsuneyuki Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, 812, Fukuoka, Japan aut NATIONALLICENCE 700 1- Ueki Showa Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University 62, 812, Fukuoka, Japan aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 106/1(1992-01-01), 31-38 0033-3158 106:1<31 1992 106 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer