TY - JOUR
T1 - Effect of cyclosporin A on morphine-induced place conditioning in mice
T2 - Involvement of nitric oxide
AU - Langroudi, Rouzbeh Motiei
AU - Khoshnoodi, Mohammad A.
AU - Abadi, Noushin Yahyavi Firouz
AU - Fahadan, Pouya Tahsili
AU - Ghahremani, Mohammad H.
AU - Dehpour, Ahmad R.
PY - 2005/1/10
Y1 - 2005/1/10
N2 - 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.
AB - 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.
KW - Aminoguanidine
KW - Conditioned place preference
KW - Cyclosporin A
KW - Morphine
KW - Neuroimmunophilin ligands
KW - Nitric oxide
KW - l-NAME (N-nitro-l-arginine methyl ester)
UR - http://www.scopus.com/inward/record.url?scp=12344262825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12344262825&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2004.11.025
DO - 10.1016/j.ejphar.2004.11.025
M3 - Article
C2 - 15659300
AN - SCOPUS:12344262825
SN - 0014-2999
VL - 507
SP - 107
EP - 115
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -