• Pouya Tahsili-Fahadan, Noushin Yahyavi-Firouz-Abadi, Amir Hossein Orandi, Behnaz Esmaeili, Zahra Basseda, and Ahmad Reza Dehpour.
• Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
• Psychopharmacology (Berl.). 2006 Apr 1;185(2):201-7.

RationaleSildenafil citrate is widely prescribed for erectile dysfunction and acts by inhibiting phosphodiesterase type-5, resulting in accumulation of cyclic-guanosine monophosphate (cGMP) via activation of nitric oxide synthase (NOS). The nitric oxide (NO) system is relevant to the rewarding effects of various drugs of abuse. Several epidemiologic studies indicate that sildenafil is abused in a recreational fashion.ObjectivesIn the present study, the rewarding properties of sildenafil and probable involvement of the NO-cGMP pathway were investigated in adult male NMRI mice.MethodsThe ability of sildenafil citrate (1-40 mg/kg) to produce conditioned place preference (CPP) was studied in an unbiased CPP paradigm. The effects of NO precursor L-arginine, nonselective NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the inhibitor of guanylyl cyclase methylene blue (MB) on sildenafil-induced CPP were assessed.ResultsMice that received sildenafil (20 and 40 mg/kg) in one environment during conditioning phase displayed a preference for this environment. Both L-NAME (5 mg/kg) and MB (1 mg/kg) in combination with sildenafil (20 mg/kg) suppressed the acquisition of sildenafil-induced place preference. Lower and per se noneffective dose of sildenafil (10 mg/kg) and L-arginine (60 mg/kg), when coadministered, exerted a significant place conditioning.ConclusionsSildenafil shows rewarding properties that may involve the NO-cGMP pathway.

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