Sildenafil and a Compound Stimulating Endothelial NO Synthase Modify Sexual Incentive Motivation and Copulatory Behavior in Male Wistar and Fisher 344 Rats


Anders Ågmo, PhD, Department of Psychology, University of Tromsø, Tromsø, Norway. Tel: +47 77646365; Fax: +47 77645291; E-mail:


Introduction.  Earlier studies have shown that sildenafil may modify some aspects of male rat sexual behavior and sexual incentive motivation. Stimulation of endothelial nitric oxide synthase (eNOS) has also been reported to affect sexual motivation in old rats.

Aim.  To determine the effects of sildenafil and a compound stimulating eNOS on copulatory behavior and sexual incentive motivation in young adult Fisher 344 and Wistar male rats.

Methods.  The rats were selected for a low intromission ratio, and then treated with Impaza (stimulator of eNOS), sildenafil, or Impaza + sildenafil for 28 days. Tests for copulatory behavior and sexual incentive motivation were performed before the beginning of treatment and at days 7, 14, and 28 of treatment.

Main Outcome Measures.  Standard parameters of copulatory behavior and sexual incentive motivation. Measurements of penis length at mount, intromission, and ejaculation.

Results.  The Fisher 344 rats displayed a higher level of sexual incentive motivation than the Wistar rats, while the copulatory behavior was similar in both strains. Impaza and sildenafil enhanced the sexual incentive motivation after 28 days of treatment in the Wistar rats, but failed to do so in the Fisher 344 rats. The copulatory behavior was unaffected in the Wistar strain, while the Fisher 344 males had an enhanced intromission ratio after treatment with Impaza and sildenafil for 28 days.

Conclusions.  The nitric oxide-guanylyl cyclase pathway seems to be of importance for sexual incentive motivation in animals with a modest baseline level. The different drug effects in the Wistar and Fisher 344 rats can be attributed to baseline differences. The importance of eNOS for sexual functions should not be overlooked. Chu X, Zhavbert ES, Dugina JL, Kheyfets IA, Sergeeva SA, Epstein OI, and Ågmo A. Sildenafil and a compound stimulating endothelial NO synthase modify sexual incentive motivation and copulatory behavior in male Wistar and Fisher 344 rats. J Sex Med 2008;5:2085–2099.