Effect of cyclosporin A on morphine-induced place conditioning in mice: involvement of nitric oxide

• Published in: European journal of pharmacology Vol. 507; no. 1; pp. 107 - 115
• Main Authors: Langroudi, Rouzbeh Motiei, Khoshnoodi, Mohammad A., Abadi, Noushin Yahyavi Firouz, Fahadan, Pouya Tahsili, Ghahremani, Mohammad H., Dehpour, Ahmad R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10-01-2005; Elsevier
• Subjects: Aminoguanidine; Animals; Biological and medical sciences; Conditioned place preference; Conditioning (Psychology) - drug effects; Conditioning (Psychology) - physiology; Cyclosporin A; Cyclosporine - pharmacology; Dose-Response Relationship, Drug; l-NAME ( NG-nitro- l-arginine methyl ester); Male; Medical sciences; Mice; Morphine; Morphine - pharmacology; Neuroimmunophilin ligands; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - physiology; Pharmacology. Drug treatments; Aminoguanidine; Neuroimmunophilin ligands; Conditioned place preference; Nitric oxide; Morphine; l-NAME ( N G -nitro- l-arginine methyl ester); Cyclosporin A; L-NAME (NG-nitro-L-arginine methyl ester); Rodentia; Opiates; Narcotic analgesic; Ester; Vertebrata; Mammalia; Arginine; Mouse; Aminoacid; Animal; Ciclosporin; Conditioning; Immunosuppressive agent
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2004.11.025

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.