title: Effect of cyclosporin A on morphine-induced place conditioning in mice: involvement of nitric oxide.
abstract: Cyclosporin A is shown to attenuate antinociceptive effects of morphine, development and expression of morphine-induced tolerance and dependency via nitric oxide (NO) pathway. In the present study, the effect of systemic cyclosporin A on morphine-induced conditioned place preference (CPP) and the probable involvement of nitric oxide were assessed in mice. Our data showed that administration of morphine (1, 2.5, 5, 7.5, 10 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. The maximum response was obtained with 5 mg/kg of morphine. Cyclosporin A (5, 10 mg/kg) and N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5, 5, 10 mg/kg), a nonselective nitric oxide synthase (NOS) inhibitor, did not induce either conditioned place preference or conditioned place aversion (CPA), while cyclosporin A (20 mg/kg) induced CPA. Both cyclosporin A (10, 20 mg/kg) and L-NAME (5, 10 mg/kg), in combination with morphine (5 mg/kg) during conditioning, significantly suppressed acquisition of morphine-induced place preference. Lower and per se noneffective doses of Cyclosporin A (1, 2.5, 5 mg/kg) and L-NAME (2.5 mg/kg), when coadministered, exerted a significant potentiating effect on the attenuation of morphine-induced place preference. Aminoguanidine (50, 100 mg/kg), the specific inducible nitric oxide synthase (iNOS) inhibitor, whether alone or in combination with cyclosporin A failed to show this inhibitory effect on morphine-induced place preference. In conclusion, decreasing nitric oxide production through inhibiting constitutive nitric oxide synthase may be a mechanism through which cyclosporin A attenuates morphine-induced place preference.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Poursina Ave., Keshavarz Blvd., Kargar Ave., P.O. Box: 13145-784 Tehran, Iran.
authors.forename: Rouzbeh
authors.initials: R
authors.lastname: Motiei Langroudi
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Khoshnoodi
authors.forename: Noushin Yahyavi Firouz
authors.initials: NY
authors.lastname: Abadi
authors.forename: Pouya
authors.initials: P
authors.lastname: Tahsili Fahadan
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Ghahremani
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D009020:Morphine; D016572:Cyclosporine; D019331:NG-Nitroarginine Methyl Ester