These effects seem to be specific for paroxetine, since another SSRI, citalopram, does not share any of the effects exerted by paroxetine on erectile function or NO production. Acknowledgments We want to acknowledge Jose L. citalopram, significantly reduced nitrite+nitrate plasma levels by 61.4% and inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after chronic treatment. The results show that paroxetine inhibits erectile responses in rats. We propose that this effect is due to reduced NO production and nNOS expression. and (Finkel and on nNOS and eNOS expression in penile tissue. Methods Male Sprague-Dawley rats were used for this study. For the chronic studies the animals were divided into three groups. The paroxetine and citalopram treated groups received a daily dose of 10?mg?kg?1 of paroxetine or citalopram by means of two intraperitoneal injections per day of 5?mg?kg?1 of the drugs dissolved in saline. The control group received two injections per day with the equivalent volume of saline. Erectile responses to cavernosal nerve activation in anaesthetized rats Male Sprague-Dawley rats were anaesthetized with urethane (1.25?g?kg?1). The surgical procedure consisted of dissection and isolation of the right cavernous nerve through an abdominal midline incision and exposure of penile crura through a transverse perineal incision. Intracavernosal pressure (ICP) measurements were accomplished by insertion into the right crus of a 23-gauge needle connected to a disposable pressure transducer (Abbott, Sligo, Ireland) and a data acquisition system (ADInstruments, Castle Hill, Australia). Right carotid artery and left external jugular vein Ocln were catheterized for constant blood pressure measurement and saline or drug infusion, respectively. Electrical activation was applied by a delicate platinum bipolar hook electrode connected to a stimulator and current amplifier (Cibertec, Madrid, Spain). Parameters of electrical activation consisted of pulses with a duration of 1 1?ms and 1.5?mA of current intensity for 1?min. Frequency?C?response curves were performed by applying stimulation at 1 and 3?Hz with an interval of 3?min between both frequencies. For evaluation of acute effects of the treatments on erectile responses, a control activation at 1 and 3?Hz was performed and, after an stabilization period, paroxetine or citalopram dissolved in 20% hydroxy-propyl-B-cyclodextrin (HPBCD) or the vehicle alone were intravenously administered. The activation was repeated at 60?min from your administration. Determination of nitrite+nitrate plasma levels Blood samples from rats treated with vehicle, paroxetine or citalopram were obtained and plasma was separated by centrifugation (1000test. Open in a separate window Physique 4 Effects of paroxetine and citalopram (10?mg?kg?1?day?1 for 2 weeks) on endothelial (A) and neuronal (B) nitric oxide synthase (NOS) expression in rat penile tissue. Data are expressed as the means.e.mean of the density of bands (in pixels). indicates the number of rats utilized for determinations. **test. Conversation The presence of adverse events affecting sexual function in patients TEPP-46 undergoing treatment with SSRIs is usually a common clinical observation (Zajecka em et al /em ., 1997; Kennedy em TEPP-46 et al /em ., 2000). The mechanism underlying increased incidence of sexual dysfunction in these patients is not well comprehended. The known mechanism of action of these drugs entails the inhibition of serotonin reuptake by neurons, increasing the levels of this neurotransmitter in the synapse. While high levels of dopamine are related to promoting sexual function, high levels of serotonin, in general, are thought to inhibit sexual behaviour (Hull em et al /em ., 1999). In relation to this fact, the increased levels of serotonin in some regions of the central nervous system could be the reason for the development of sexual dysfunction associated with SSRIs. Nevertheless, although all SSRIs enhance serotonin TEPP-46 levels in the brain not all of them produce the same effects on sexual function. Indeed, an increase of incidence of erectile dysfunction in patients treated with paroxetine has often been reported, while a lesser effect of citalopram on sexual function has also been published (Mendels em et al /em ., 1999). Furthermore, the activation of some.