The effect of drugs that alter serotonin homeostasis in rat erectile function

Abstract

We investigated wether antidepressants that alter serotonin (5‐hydroxytryptamine; 5‐HT) homeostasis impact rat erection due to 5‐HT uptake and metabolism in the penile dorsal vein (PDV). 5‐HT and its metabolite 5‐hydroxyindole acetic acid (5‐HIAA) were measured by high performance liquid chromatography in rat PDV. Exposure to exogenous 5‐HT increased 5‐HIAA but not 5‐HT content in PDV, suggesting uptake followed by metabolism, and this was supported by increased 5‐HT and decreased 5‐HIAA content induced by pargyline, a monoamine oxidase inhibitor (enzyme that metabolizes 5‐HT). Fluoxetine (5‐HT uptake transporter inhibitor) and imipramine (norepinephrine and 5‐HT uptake transporters inhibitor) did not inhibit 5‐HT uptake in PDV. Concentration effect curve (CEC) induced by 5‐HT was also evaluated in endothelium‐intact rings of PDV in the presence of fluoxetine, imipramine and pargyline. The CEC induced by 5‐HT was shifted to the right by imipramine and unchanged by pargyline. Fluoxetine increased the maximal contraction induced by 5‐HT in PDV. The effect of these drugs was also evaluated in the erections induced by apomorphine in conscious rats. Pargyline decreased, fluoxetine increased and imipramine had no effect in the number of erections induced by apomorphine. As apomorphine, fluoxetine per se induced ~3 erections/rat. Altogether, drugs that alter 5‐HT homeostasis in PDV do impact erection. CAPES; FAPESC.