Article

Phosphodiesterase Type 5 Inhibitors Facilitate Noncontact Erections in Male Rats: Site of Action in the Brain and Mechanism of Action

Bernard B. Brodie Department of Neuroscience, University of Cagliari, Monserrato, Cagliari 09042, Italy.
Journal of Sexual Medicine (Impact Factor: 3.15). 09/2009; 6(10):2680-9. DOI: 10.1111/j.1743-6109.2009.01410.x
Source: PubMed

ABSTRACT Orally active phosphodiesterase type 5 inhibitors (PDE5i), used in the treatment of erectile dysfunction, facilitate the relaxation of cavernous smooth muscle tissues by reducing the degradation of cyclic guanosine monophosphate.
The aims of this article were to determine whether PDE5i facilitate penile erection and male sexual behavior by acting also on the central nervous system and to investigate their mechanism of action at central level.
PDE5i (sildenafil, vardenafil, and tadalafil) given intraperitoneally (i.p.) (5 mg/kg and 10 mg/kg), intracerebroventricularly (i.c.v.) (10 microg and 50 microg), or into the ventral tegmental area (VTA) (10 microg) were tested in the noncontact erection test in male Sprague-Dawley rats screened for their ability to display or not display this sexual response. Extracellular dopamine was measured in the dialysate obtained from the nucleus accumbens by intracerebral microdialysis on injection of PDE5i into the VTA. MAIN OUTCOME MEASURES. Noncontact erections were counted after intraperitoneal, intracerebroventricular, or intra-VTA treatment with PDE5i. Extracellular dopamine was measured in the dialysate from the nucleus accumbens when sildenafil or vardenafil was given into the VTA. Results. PDE5i induced a significant increase of noncontact erections in male rats displaying this sexual response following intraperitoneal or intracerebroventricular administration at the highest dose tested. However, both doses significantly increased noncontact erections in male rats not displaying this sexual response. Similar results were found when PDE5i were injected into the caudal VTA. Noncontact erections increased concomitantly to a rise in extracellular dopamine in the dialysate from the nucleus accumbens.
The results suggest that PDE5i may increase sexual arousal by acting in the central nervous system. This effect may be mediated (at least in part) by the activation of mesolimbic dopaminergic neurons.

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    • "These differences are likely to contribute to the different properties of these drugs. Centrally, both Sildenafil and Vardenafil are capable of crossing the blood brain barrier and affecting central PDE-5, which is expressed in different brain areas [24] [25] [26] [27] underlying modulation of behaviors, such as rage, emotion and sexual drive. In a recent animal study [28], we reported that Sildenafil counteracts the inhibitory effects of chronic social subordination on modulation of competitive aggression by restoring both aggressive and sexual behavior in subordinated male mice. "
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    • "A group of vehicle-treated SE rats (n ¼9) was used as a reference for optimal sexual performance under physiological conditions. Dosages of Turnera diffusa and sildenafil were selected based on previous observations (Estrada- Reyes et al., 2009; Sanna et al., 2009). All solutions were administered in a volume of 2 mL/kg of body weight. "
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