Vardenafil Enhances Oxytocin Expression in the Paraventricular Nucleus without Sexual Stimulation.
OBJECTIVE
Oxytocin is associated with the ability to form normal social attachments. c-Fos is an immediate early gene whose expression is used as a marker for stimulus-induced changes in neurons. The effect of phosphodiesterase-5 (PDE-5) inhibitors on oxytocin activation in the brain without sexual stimuli has not yet been reported. In the present study, we investigated the effects of vardenafil on oxytocin and c-Fos expression in the paraventricular nucleus (PVN) of conscious rats.


METHODS
Male Sprague-Dawley rats weighing 300±10 g were divided into 6 groups (n=5 in each group): the control group, the 1-day-0.5 mg/kg, the 1-day-1 mg/kg, the 1-day-2 mg/kg, the 3-day-1 mg/kg, and the 7-day-1 mg/kg vardenafil administration group. The experiment was conducted without sexual stimulation. Vardenafil was orally administered. The animals in the control group received an equivalent amount of distilled water orally. The expression of oxytocin and c-Fos in the PVN was detected by immunohistochemistry.


RESULTS
Oxytocin expression in the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil appeared in a duration-dependent manner. c-Fos in the oxytocin neurons of the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil also appeared in a duration-dependent manner. These results showed that vardenafil augments the expression of oxytocin with activation of oxytocin neurons in the PVN.


CONCLUSIONS
In this study, we showed that the PDE-5 inhibitor, vardenafil directly enhances oxytocin expression and also activates oxytocin neurons in the PVN, which indicates that vardenafil may exert positive effects on affiliation behavior and social interaction.
Department of Physiology, Kyung Hee University School of Medicine, Seoul, Korea.
Mal Soon
MS
Shin
Il Gyu
IG
Ko
Yun Hee
YH
Sung
Sung Eun
SE
Kim
Bo Kyun
BK
Kim
Chang Ju
CJ
Kim
Sang Won
SW
Lee
Dong Hee
DH
Kim
Joo Hyun
JH
Chang
Khae Hawn
KH
Kim
Science. 2005 Apr 8;308(5719):245-8
15821089
Psychoneuroendocrinology. 1998 Nov;23(8):819-35
9924739
Trends Neurosci. 1989 Nov;12(11):459-62
2479148
Psychoneuroendocrinology. 1998 Nov;23(8):779-818
9924738
Physiol Rev. 2001 Apr;81(2):629-83
11274341
Ned Tijdschr Geneeskd. 2006 Jul 22;150(29):1613-6
16901064
Psychoneuroendocrinology. 1992;17(1):3-35
1319071
Brain Res. 2009 Apr 10;1265:148-57
19368809
Pharmacol Biochem Behav. 1990 Sep;37(1):63-9
2263668
Horm Behav. 1999 Dec;36(3):212-21
10603285
Neurosci Biobehav Rev. 1999 Dec;23(8):1127-42
10643821
Neuroendocrinology. 1987 Jun;46(1):56-61
3614555
Life Sci. 2003 Oct 31;73(24):3139-47
14550853
Neuroscience. 1995 Jan;64(2):477-505
7700534
BJU Int. 2008 Jan;101(2):203-10
17888043
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17237-40
16303870
Neuropsychopharmacology. 2005 Oct;30(10):1883-94
15798779
Neurosci Biobehav Rev. 1995 Summer;19(2):303-14
7630584
Nature. 2005 Jun 2;435(7042):673-6
15931222
Horm Behav. 2005 Dec;48(5):522-7
16109416
Curr Urol Rep. 2003 Dec;4(6):479-87
14622502
Front Neuroendocrinol. 2004 Sep-Dec;25(3-4):150-76
15589267
Biol Psychiatry. 2003 Dec 15;54(12):1389-98
14675803
Expert Opin Pharmacother. 2007 May;8(7):965-74
17472542
Pharmacol Biochem Behav. 1992 Nov;43(3):855-61
1448480
J Clin Neurosci. 2010 Aug;17(8):1038-41
20627581
Ann N Y Acad Sci. 1997 Jan 15;807:126-45
9071347
Urology. 2006 Aug;68(2):429-35
16904479
J Sex Marital Ther. 1999 Apr-Jun;25(2):145-50
10327384
J Neurosci Methods. 1989 Sep;29(3):261-5
2507830
J Physiol Pharmacol. 2003 Dec;54(4):653-60
14726618
J Clin Endocrinol Metab. 2001 Oct;86(10):4798-804
11600543
Neurosci Biobehav Rev. 2001 Dec;25(7-8):679-85
11801293
Acta Physiol Scand. 1986 Feb;126(2):225-30
2871695
Prog Brain Res. 2002;139:147-62
12436933