Differential effects of serotonin reuptake inhibitors on erectile responses, NO-production, and neuronal NO synthase expression in rat corpus cavernosum tissue

Increased incidence of impotence is associated with some selective scrotoni n-reuptake-inhibitors (SSRIs), but the pathophysiological mechanism is unkn own, Paroxetine and citalopram are extensively used SSRIs, but only paroxet ine has been shown to inhibit nitric oxide synthase (NOS) activity. NO is a key mediator of penile erection. Thus, the aim of this study was to determ ine the effects of paroxetine and citalopram on erectile function and NO pr oduction, in a rat model. Application of cavernosal nerve electrical stimul ation produced frequency-related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor, N-G-nitro-L-arginine (0.3 mg kg( -1)). Acute or chronic (2 weeks) paroxetine-treatment (10 mg kg(-1)) reduce d ICP-responses, while citalopram did not. Paroxetine, but not citalopram, significantly reduced nitrite+nitrate plasma levels by 61.4% and inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after chronic treatm ent. The results show that paroxetine inhibits erectile responses in rats. We propose that this effect is due to reduced NO production and nNOS expres sion.