The effects of sildenafil after chronic L-NAME administration in male rat sexual behavior.

Ferraz MMD, Quintella SL, Parcial ALN, Ferraz MR. The effects of sildenafil citrate and L-NAME on male rat sexual behaviour. PHARMACOL BIOCHEM BEHAV. Erectile dysfunction (ED) affects up to 50% of men between 40 and 70years of age. Significant advances in the pharmacological treatment of ED occurred in recent years, most notably the introduction of the first oral selective phosphodiesterase type-5 inhibitor, sildenafil. This study investigated the effectiveness of chronic oral treatment with L-NAME in rats as an experimental model of erectile dysfunction to evaluate new pharmacological agents that affect the sexual response. The effects of chronic oral L-NAME treatment, separately or in combination with sildenafil, on the sexual behaviour of male rats were evaluated. Filtered water was used as a control. Acute administration of L-NAME did not alter the sexual response compared with control, but sildenafil administration facilitated sexual behaviour after acute and chronic administration. Chronic L-NAME treatment inhibited motivational and consummatory measures of male rat sexual behaviour. Sildenafil prevented the inhibitory effects of L-NAME. The present results confirm that chronic oral treatment with a nitric oxide synthase inhibitor may be a relevant peripheral ED model to evaluate the effects of drugs on erectile function of male rats.

Prenatal Hypoxia Ischemia Increases Male Rat Sexual Behavior.

INTRODUCTION: Research consistently indicates an association between prenatal hypoxia-ischemia (HI) and mortality and chronic neurological diseases in newborns. HI can cause permanent effects, including mental retardation, motor impairment, learning disabilities, epilepsy, and cerebral palsy. Moreover, little is known about the relationship between HI and sexual behavior. AIMS: The aims of this study are to examine whether HI is associated with changes in sexual behavior. METHODS: HI was induced by clamping the uterine arteries of pregnant rats. The arteries were clamped for 45 minutes on the 18th day of gestation (HI group). Shams received laparotomy and anesthesia only. Pups were born at term. At 90 days of age, sexual behavior was evaluated. Statistical analysis was performed using two-way analysis of variance and post hoc Bonferonni correction. MAIN OUTCOME MEASURES: The main outcome measures of sexual response were standard sexual behavior, homosexual behavior, and sexual attempt on nonreceptive females. RESULTS: The stimulatory effect of HI on male rat sexual behavior has been shown in various experimental models; these animals showed reduced mount, intromission and ejaculation latencies; increased copulatory efficiency; and homosexual mounting. Additionally, there was an increase in fighting in trying to mount an unreceptive female. CONCLUSION: Our results indicate that HI had a long-term effect on sexual behavior despite exhibiting motor skill impairment. Accordingly, injuries during the fetal period may cause behavioral problems in adulthood.

Nitric oxide modulates the hyperalgesic response to mechanical noxious stimuli in sleep-deprived rats.

BACKGROUND: Sleep restriction alters pain perception in animals and humans, and many studies have indicated that paradoxical sleep deprivation (PSD) promotes hyperalgesia. The hyperalgesia observed after mechanical nociceptive stimulus is reversed through nitric oxide synthase (NOS) inhibition. Both nitric oxide (NO) and the dorsolateral periaqueductal gray matter (dlPAG) area of the brainstem are involved in hyperalgesia. Thus, in this work, we investigated the pain-related behavior response after mechanical noxious stimuli (electronic von Frey test), and the activity of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), an indicator of NOS activity, within the dlPAG of paradoxical sleep-deprived rats. We also evaluated the effects of pre-treatment with L-NAME on these parameters. RESULTS: These data revealed that PSD reduced the hindpaw withdrawal threshold (-47%, p < 0.0001) confirming the hyperalgesic effect of this condition. In addition, there were more NADPH-d positive cells in dlPAG after PSD than in control rats (+ 59%, p < 0.0001). L-NAME treatment prevented the reduction in the hindpaw withdrawal threshold (+ 93%, p < 0.0001) and the increase in the NADPH-d positive cells number in the dlPAG of PSD-treated rats (-36%, p < 0.0001). CONCLUSION: These data suggest that the hyperalgesic response to mechanical noxious stimuli in paradoxical sleep-deprived rats is associated with increased NOS activity in the dlPAG, which presumably influences the descending antinociceptive pathway.