Sildenafil and a Compound Stimulating Endothelial NO Synthase Modify Sexual Incentive Motivation and Copulatory Behavior in Male Wistar and Fisher 344 Rats Xi Chu, MSc,* Ekaterina S. Zhavbert, MSc, † Julia L. Dugina, MD, PhD, † Irina A. Kheyfets, MSc, † Svetlana A. Sergeeva, PhD, † Oleg I. Epstein, MD, PhD, † and Anders Ågmo, PhD ‡ *Department of Medical Physiology, University of Tromsø, Tromsø, Norway; † OOO NPF Materia Medica Holding Company, R and D Department, Moscow, Russia; ‡ Department of Psychology, University of Tromsø, Tromsø, Norway DOI: 10.1111/j.1743-6109.2008.00937.x ABSTRACT 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. Measure- ments 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. Key Words. Sexual Incentive Motivation; Sexual Behavior; Endothelial NO Synthase; Sildenafil; Erection Introduction A common consequence of the clinical use of proerectile drugs is that the frequency of penile-vaginal intercourse is increased in the men taking such drugs (e.g., [1]). An equally common explanation for this fact is that the enhanced inter- course frequency is a result of improved erection, making this kind of sexual activity possible. It could also be maintained that proerectile drugs enhance sexual motivation, which would facilitate erection as well as the desire to use it for inter- course. However, a majority of clinical data suggest that proerectile drugs do not enhance sexual motivation. This assertion applies both to the most commonly used treatments for erectile deficiency, the phosphodiesterase type 5 (PDE5) inhibitors, as well as to the centrally acting agent apomorphine (e.g., [1,2]). To the contrary, results from experimental studies in rodents suggest that 2085 © 2008 International Society for Sexual Medicine J Sex Med 2008;5:2085–2099