HP-1-6 Dual Effect of the Serotonin and Dopamine Reuptake Inhibitor, IP2018 on Depression and Erectile Function in Rats

Abstract

The present study investigated whether a newly developed amine transport inhibitor, IP2018, improves depression and erectile function in the same dose range. The dose-dependent effect of IP2018 in two different mouse models for depression the mouse forced swim test (mFST) and mouse tail suspension test (mTST) is reported. In male Wistar rats increases in intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured and the ratio ICP/MAP used as a measure of erectile function. It was investigated whether IP2018 induces changes in ICP and whether IP2018 facilitate suboptimal increases in ICP induced by cavernosal nerve electrical stimulation. Infusion of IP2018 dose-dependently improved mFST and was more potent than cipramil, while higher doses of IP2018 were required to obtain effect in the mTST model and IP2018 was equipotent to cipramil. Infusion of low doses of IP2018 dose-dependently increased the number and the duration of spontaneous erections. At the highest dose of IP2018 infused, the increases in number and duration of spontaneous erections were similar to the effect of the lowest. The occurrence and the magnitude of spontaneous erectile responses after infusion of 1 mg/kg IP2018 were larger in 6 weeks-old versus 12-13 week old rats. Suboptimal stimulation of the cavernous nerve induced reproducible increases in ICP/MAP that were unchanged in the presence of IP2018. IP2018 (1-30 μM) only caused small relaxations in isolated corpus cavernosum strips.