PMID- 23347260 OWN - NLM STAT- MEDLINE DCOM- 20131017 LR - 20130415 IS - 1460-9568 (Electronic) IS - 0953-816X (Linking) VI - 37 IP - 8 DP - 2013 Apr TI - Differential effects of site-specific knockdown of estrogen receptor alpha in the medial amygdala, medial pre-optic area, and ventromedial nucleus of the hypothalamus on sexual and aggressive behavior of male mice. PG - 1308-19 LID - 10.1111/ejn.12131 [doi] AB - Testosterone is known to play an important role in the regulation of male-type sexual and aggressive behavior. As an aromatised metabolite of testosterone, estradiol-induced activation of estrogen receptor alpha (ERalpha) may be crucial for the induction of these behaviors in male mice. However, the importance of ERalpha expressed in different nuclei for this facilitatory action of testosterone has not been determined. To investigate this issue, we generated an adeno-associated virus vector expressing a small hairpin RNA targeting ERalpha to site-specifically knockdown ERalpha expression. We stereotaxically injected either a control or ERalpha targeting vector into the medial amygdala, medial pre-optic area (MPOA), or ventromedial nucleus of the hypothalamus (VMN) in gonadally intact male mice. Two weeks after injection, all mice were tested biweekly for sexual and aggressive behavior, alternating between behavior tests each week. We found that suppressing ERalpha in the MPOA reduced sexual but not aggressive behavior, whereas in the VMN it reduced both behaviors. Knockdown of ERalpha in the medial amygdala did not alter either behavior. Additionally, it was found that ERalpha knockdown in the MPOA caused a parallel reduction in the number of neuronal nitric oxide synthase-expressing cells. Taken together, these results indicate that the testosterone facilitatory action on male sexual behavior requires the expression of ERalpha in both the MPOA and VMN, whereas the testosterone facilitatory action on aggression requires the expression of ERalpha in only the VMN. CI - (c) 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. FAU - Sano, Kazuhiro AU - Sano K AD - Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Ibaraki, Japan. FAU - Tsuda, Mumeko C AU - Tsuda MC FAU - Musatov, Sergei AU - Musatov S FAU - Sakamoto, Toshiro AU - Sakamoto T FAU - Ogawa, Sonoko AU - Ogawa S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130124 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Estrogen Receptor alpha) RN - 0 (RNA, Small Interfering) SB - IM MH - Aggression/*physiology MH - Animals MH - Brain/*metabolism MH - Estrogen Receptor alpha/*metabolism MH - Gene Knockdown Techniques MH - Immunohistochemistry MH - Male MH - Mice MH - RNA, Small Interfering MH - Sexual Behavior, Animal/*physiology EDAT- 2013/01/26 06:00 MHDA- 2013/10/18 06:00 CRDT- 2013/01/26 06:00 PHST- 2012/09/19 00:00 [received] PHST- 2012/12/11 00:00 [revised] PHST- 2012/12/17 00:00 [accepted] PHST- 2013/01/26 06:00 [entrez] PHST- 2013/01/26 06:00 [pubmed] PHST- 2013/10/18 06:00 [medline] AID - 10.1111/ejn.12131 [doi] PST - ppublish SO - Eur J Neurosci. 2013 Apr;37(8):1308-19. doi: 10.1111/ejn.12131. Epub 2013 Jan 24.