Role of 5-HT receptor antagonists in mediating intracavernous pressure response induced by fluvoxamine in conscious rats.
BACKGROUND
It has been reported that selective serotonin reuptake inhibitor (SSRI) may cause sexual dysfunction.


OBJECTIVE
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-HT(1A)-receptor antagonist), and SB242084 (a 5-HT(2C)-receptor antagonist) were administered by intravenous (i.v.) or intracerebroventricular (i.c.v.) routes.


METHODS
BP and parameters of ICP were measured in conscious and free-moving rats.


RESULTS
Administration of fluvoxamine (1- to 30-micromol/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-HT(2C)-receptors and inhibited by 5-HT(1A)-receptors in the rat brain.
Aizawa
Naoki
N
Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan. n-aizawa@hsp.md.shinshu-u.ac.jp
Ishizuka
Osamu
O
Ogawa
Teruyuki
T
Mizusawa
Hiroya
H
Igawa
Yasuhiko
Y
Nishizawa
Osamu
O
D000631:Aminopyridines / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016666:Fluvoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D010413:Penis / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced*
D000631:Aminopyridines; D016666:Fluvoxamine; D007211:Indoles; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide