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

Rouzbeh Motiei Langroudi, Mohammad A. Khoshnoodi, Noushin Yahyavi Firouz Abadi, Pouya Tahsili Fahadan, Mohammad H. Ghahremani, Ahmad R. Dehpour

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 NG-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.

Original languageEnglish (US)
Pages (from-to)107-115
Number of pages9
JournalEuropean Journal of Pharmacology
Issue number1-3
StatePublished - Jan 10 2005
Externally publishedYes


  • Aminoguanidine
  • Conditioned place preference
  • Cyclosporin A
  • Morphine
  • Neuroimmunophilin ligands
  • Nitric oxide
  • l-NAME (N-nitro-l-arginine methyl ester)

ASJC Scopus subject areas

  • Pharmacology


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