Role of 5-HT Receptor Antagonists in Mediating Intracavernous Pressure Response Induced by Fluvoxamine in Conscious Rats

Authors


Naoki Aizawa, Department of Urology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. Tel: +81-263-37-2661; Fax: +81-263-37-3082; E-mail: n-aizawa@hsp.md.shinshu-u.ac.jp

ABSTRACT

Introduction.  It has been reported that selective serotonin reuptake inhibitor (SSRI) may cause sexual dysfunction.

Aim.  To determine the relationship between serotonin and sexual function, we investigated the role of serotonergic receptors on changes in intracavernous pressure (ICP) and systemic blood pressure (BP) in conscious and free-moving rats.

Methods.  ICP and BP were measured in male Sprague-Dawley rats after catheters were inserted into the crus corpus cavernosum and carotid artery, respectively. Pressures were recorded 2 hours after catheterization. In other rats, this procedure was performed 2 weeks after spinal cord transection (spinal cord injury [SCI]) between the eighth and ninth thoracic vertebrae. To investigate the role of serotonergic receptors, fluvoxamine (an SSRI), WAY100635 (a 5-HT1A-receptor antagonist), and SB242084 (a 5-HT2C-receptor antagonist) were administered by intravenous (i.v.) or intracerebroventricular (i.c.v.) routes.

Main Outcome Measures.  BP and parameters of ICP were measured in conscious and free-moving rats.

Results.  Administration of fluvoxamine (1- to 30-μmol/kg i.v. and 1- to 30-nmol i.c.v.) induced a transient increase in the ICP. The ICP parameters responded in a dose-dependent manner, especially the time to first response (TFR), which was significantly shortened. BP also increased in response to fluvoxamine. In contrast, ICP in SCI rats did not change after fluvoxamine administration. WAY100635 (10 or 30-nmol i.c.v.) induced an increase in the ICP. In combination with fluvoxamine, it significantly shortened the TFR in comparison with WAY100635 or fluvoxamine alone. However, SB242084 (10 or 30-nmol i.c.v.) actually had an inhibitory effect on fluvoxamine-induced ICP responses.

Conclusions.  These findings demonstrated that ICP is regulated at the supraspinal level when endogenous serotonin is increased by fluvoxamine. Furthermore, ICP is facilitated by 5-HT2C-receptors and inhibited by 5-HT1A-receptors in the rat brain. Aizawa N, Ishizuka O, Ogawa T, Mizusawa H, Igawa Y, and Nishizawa O. Role of 5-HT receptor antagonists in mediating intracavernous pressure response induced by fluvoxamine in conscious rats. J Sex Med 2007;4:1108–1116.

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