Involvement of nitric oxide system in enhancement of morphine-induced conditioned place preference by agmatine in male mice

Agmatine recently has been suggested as a neurotransmitter, is able to interact with various effects of morphine like analgesia and dependence. In this study, the effects of agmatine on rewarding properties of morphine, and the possible involvement of nitric oxide (NO) system has been evaluated in an unbiased conditioned place preference (CPP) paradigm. Agmatine (1, 5 and 10 mg/kg, i.p.) alone induced neither CPP nor conditioned place aversion (CPA). Morphine (0.01, 0.05, 0.1 and 0.5 mg/kg, s.c.), while unable to show CPP or CPA, induced CPP in mice pretreated with agmatine. L-arginine (200 mg/kg, i.p.), a NO precursor, significantly enhanced the effect of agmatine (5 mg/kg) on morphine (0.5 mg/kg)-induced place preference. NG-nitro-l-arginine methyl ester (l-NAME; 2.5 mg/kg, i.p.), a non specific nitric oxide synthase (NOS) inhibitor, and aminoguanidine (50 and 100 mg/kg, i.p.), a specific inducible NOS inhibitor, significantly reduced the effect of agmatine (5 mg/kg) on morphine (0.5 mg/kg)-induced place preference. These results suggest the possible involvement of inducible nitric oxide system in potentiating effects of agmatine on morphine-induced place preference.