Vardenafil increases cell proliferation in the dentate gyrus through enhancement of serotonin expression in the rat dorsal raphe.
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.
Kim
Tae-Soo
TS
Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea.
Ko
Il-Gyu
IG
Sung
Yun-Hee
YH
Kim
Sung-Eun
SE
Kim
Bo-Kyun
BK
Park
Seung-Kook
SK
Shin
Mal-Soon
MS
Kim
Chang-Ju
CJ
Yoon
Sang-Jin
SJ
Kim
Khae-Hawn
KH
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
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D012701:Serotonin; D000069058:Vardenafil Dihydrochloride; D014365:Tryptophan Hydroxylase