J Korean Med Sci.  2009 Dec;24(6):1099-1104. 10.3346/jkms.2009.24.6.1099.

Vardenafil Increases Cell Proliferation in the Dentate Gyrus through Enhancement of Serotonin Expression in the Rat Dorsal Raphe

• Kim TS
• Ko IG
• Sung YH
• Kim SE
• Kim BK
• Park SK
• Shin MS
• Kim CJ
• Yoon SJ
• Kim KH

• KMID: 1783139
• DOI: http://doi.org/10.3346/jkms.2009.24.6.1099

Abstract

This study was conducted to evaluate the effects of vardenafil (Levitra), a phosphodiesterase-5 (PDE-5) inhibitor, on cell proliferation in the hippocampal dentate gyrus and on 5-hyroxytryptamine (5-HT, serotonin) synthesis and tryptophan hydroxylase (TPH) expression in the rat dorsal raphe nucleus. Male Sprague-Dawley rats were divided into 6 groups (n=5 in each group): a control group, a 0.5 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-1 day vardenafil-treated group, a 2 mg/kg-1 day vardenafil-treated group, a 1 mg/kg-3 day vardenafil-treated group, and a 1 mg/kg-7 day vardenafil-treated group. 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry was then performed to evaluate cell proliferation in the dentate gyrus. In addition, 5-HT and TPH immunohistochemistry was conducted to evaluate serotonin expression in the dorsal raphe. The results revealed that treatment with vardenafil increased cell proliferation in the dentate gyrus and enhanced 5-HT synthesis and TPH expression in the dorsal raphe in a dose- and duration-dependent manner. The findings demonstrate that the increasing effect of vardenafil on cell proliferation is closely associated with the enhancing effect of vardenafil on serotonin expression under normal conditions.

Keyword

Vardenafil; Dentate Gyrus; Cell Proliferation; Serotonin; Tryptophan Hydroxylase

MeSH Terms

Animals
Cell Proliferation/*drug effects
*Dentate Gyrus/cytology/drug effects/metabolism
Imidazoles/*pharmacology
Male
Phosphodiesterase Inhibitors/*pharmacology
Piperazines/*pharmacology
*Raphe Nuclei/cytology/drug effects/metabolism
Rats
Rats, Sprague-Dawley
Serotonin/*biosynthesis
Sulfones/pharmacology
Triazines/pharmacology
Tryptophan Hydroxylase/metabolism

Figure

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  Fig. 1 Effect of vardenafil treatment on cell proliferation in the dentate gyrus. Above: Photomicrographs of 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus. 1. Control group, 2. 2 mg/kg vardenafil for 1 day-treated group. The scale bar represents 50 µm. Middle: The dose-dependent effect of vardenafil treatment for 1 day on cell proliferation in the dentate gyrus. (A) Control group, (B) 0.5 mg/kg vardenafil-treated group, (C) 1 mg/kg vardenafil-treated group, (D) 2 mg/kg vardenafil-treated group. Lower: The duration-dependent effect of 1 mg/kg vardenafil treatment on cell proliferation in the dentate gyrus. (A) Control group, (B) 1-day vardenafil-treated group, (C) 3-day vardenafil-treated group, (D) 7-day vardenafil-treated group. Values are represented as the mean±SEM.

• 

  Fig. 2 Effect of vardenafil treatment on 5-hyroxytryptamine (5-HT) expression in the dorsal raphe nucleus. Upper: Photomicrographs of 5-HT-positive cells in the dorsal raphe nucleus. 1. Control group, 2. 2 mg/kg vardenafil for 1 day-treated group. The scale bar represents 100 µm. Middle: The dose-dependent effect of 1-day vardenafil treatment on 5-HT expression in the dorsal raphe nucleus. (A) Control group, (B) 0.5 mg/kg vardenafil-treated group, (C) 1 mg/kg vardenafil-treated group, (D) 2 mg/kg vardenafil-treated group. Lower: The duration-dependent effect of 1 mg/kg vardenafil treatment on 5-HT expression in the dorsal raphe nucleus. (A) Control group, (B) 1-day vardenafil-treated group, (C) 3-day vardenafil-treated group, (D) 7-day vardenafil-treated group. Values are represented as the mean±SEM.

• 

  Fig. 3 Upper: Photomicrographs of tryptophan hydroxylase (TPH)-positive cells in the dorsal raphe nucleus. 1. Control group, 2. 2 mg/kg vardenafil for 1 day-treated group. The scale bar represents 100 mm. Middle: The dose-dependent effect of 1-day vardenafil treatment on TPH expression in the dorsal raphe nucleus. (A) Control group, (B) 0.5 mg/kg vardenafil-treated group, (C) 1 mg/kg vardenafil-treated group, (D) 2 mg/kg vardenafil-treated group. Lower: The duration-dependent effect of 1 mg/kg vardenafil treatment on TPH expression in the dorsal raphe nucleus. (A) Control group, (B) 1-day vardenafil-treated group, (C) 3-day vardenafil-treated group, (D) 7-day vardenafil-treated group. Values are represented as the mean±SEM.

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