title: Vardenafil increases cell proliferation in the dentate gyrus through enhancement of serotonin expression in the rat dorsal raphe.
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.
authors: Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors: Tae-Soo
authors: TS
authors: Kim
authors: Il-Gyu
authors: IG
authors: Ko
authors: Yun-Hee
authors: YH
authors: Sung
authors: Sung-Eun
authors: SE
authors: Kim
authors: Bo-Kyun
authors: BK
authors: Kim
authors: Seung-Kook
authors: SK
authors: Park
authors: Mal-Soon
authors: MS
authors: Shin
authors: Chang-Ju
authors: CJ
authors: Kim
authors: Sang-Jin
authors: SJ
authors: Yoon
authors: Khae-Hawn
authors: KH
authors: Kim
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D013450:Sulfones / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014365:Tryptophan Hydroxylase / Q000378:metabolism; D000069058:Vardenafil Dihydrochloride
chemical_list: D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D012701:Serotonin; D000069058:Vardenafil Dihydrochloride; D014365:Tryptophan Hydroxylase