Differential effects of site-specific knockdown of estrogen receptor α in the medial amygdala, medial pre-optic area, and ventromedial nucleus of the hypothalamus on sexual and aggressive behavior of male mice

European Journal of Neuroscience

Volumn 37, Issue 8, 2013, Pages 1308-1319

  Sano, Kazuhiro ^a   Tsuda, Mumeko C ^a   Musatov, Sergei ^b   Sakamoto, Toshiro ^a   Ogawa, Sonoko ^a  

^a UNIVERSITY OF TSUKUBA   (Japan)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Adeno associated virus mediated RNA interference; Estrogen receptor ; Neuronal nitric oxide synthase; Social behavioral network; Testosterone

Indexed keywords

ESTROGEN RECEPTOR ALPHA; NEURONAL NITRIC OXIDE SYNTHASE; PARVOVIRUS VECTOR; SHORT HAIRPIN RNA;

AGGRESSION; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BEHAVIOR CONTROL; BODY WEIGHT; CONTROLLED STUDY; GENE INACTIVATION; GENE SILENCING; HYPOTHALAMUS VENTROMEDIAL NUCLEUS; IMMUNOHISTOCHEMISTRY; MALE; MEDIAL AMYGDALA; MEDIAL PREOPTIC AREA; MOUSE; NONHUMAN; PRIORITY JOURNAL; SEXUAL BEHAVIOR;

AGGRESSION; ANIMALS; BRAIN; ESTROGEN RECEPTOR ALPHA; GENE KNOCKDOWN TECHNIQUES; IMMUNOHISTOCHEMISTRY; MALE; MICE; RNA, SMALL INTERFERING; SEXUAL BEHAVIOR, ANIMAL;

EID: 84876343031     PISSN: 0953816X     EISSN: 14609568     Source Type: Journal    
DOI: 10.1111/ejn.12131     Document Type: Article

References (65)

1. Bakker, J., Honda, S., Harada, N. & Balthazart, J. (2004) Restoration of male sexual behavior by adult exogenous estrogens in male aromatase knockout mice. Horm. Behav., 46, 1-10.
2. Baum, M.J. (2003) Activational and organizational effects of estradiol on male behavioral neuroendocrine function. Scand. J. Psychol., 44, 213-220.
3. Been, L.E. & Petrulis, A. (2011) Chemosensory and hormone information are relayed directly between the medial amygdala, posterior bed nucleus of the stria terminalis, and medial preoptic area in male Syrian hamsters. Horm. Behav., 59, 536-548.
4. Benelli, A., Bertolini, A., Poggioli, R., Cavazzuti, E., Calza, L., Giardino, L. & Arletti, R. (1995) Nitric oxide is involved in male sexual behavior of rats. Eur. J. Pharmacol., 294, 505-510.
5. Blanchard, R.J., Wall, P.M. & Blanchard, D.C. (2003) Problems in the study of rodent aggression. Horm. Behav., 44, 161-170.
6. Coolen, L.M. & Wood, R.I. (1998) Bidirectional connections of the medial amygdaloid nucleus in the Syrian hamster brain: simultaneous anterograde and retrograde tract tracing. J. Comp. Neurol., 399, 189-209.
7. Coolen, L.M., Peters, H.J. & Veening, J.G. (1997) Distribution of Fos immunoreactivity following mating versus anogenital investigation in the male rat brain. Neuroscience, 77, 1151-1161.
8. Delville, Y., De Vries, G.J. & Ferris, C.F. (2000) Neural connections of the anterior hypothalamus and agonistic behavior in golden hamsters. Brain Behav. Evol., 55, 53-76.
9. Haller, J. & Kruk, M.R. (2006) Normal and abnormal aggression: human disorders and novel laboratory models. Neurosci. Biobehav. Rev., 30, 292-303.
10. Harding, S.M. & McGinnis, M.Y. (2004) Androgen receptor blockade in the MPOA or VMN: effects on male sociosexual behaviors. Physiol. Behav., 81, 671-680.
11. Heine, P.A., Taylor, J.A., Iwamoto, G.A., Lubahn, D.B. & Cooke, P.S. (2000) Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc. Natl. Acad. Sci. USA, 97, 12729-12734.
12. Huddleston, G.G., Paisley, J.C. & Clancy, A.N. (2006) Effects of estrogen in the male rat medial amygdala: infusion of an aromatase inhibitor lowers mating and bovine serum albumin-conjugated estradiol implants do not promote mating. Neuroendocrinology, 83, 106-116.
13. Hull, E.M. & Dominguez, J.M. (2007) Sexual behavior in male rodents. Horm. Behav., 52, 45-55.
14. Hull, E.M., Meisel, R.L. & Sachs, B.D. (2002) Male sexual behavior. In Pfaff, D.W., Arnold, A.P., Etgen, A.M., Fahrbach, S.E. & Rubin, R.T. (Eds), Hormones, Brain and Behavior. vol. 1. Academic Press, San Diego, CA, pp. 3-137.
15. Hull, E.M., Wood, R.I. & McKenna, K. (2006) The neurobiology of male sexual behavior. In Neill, J.D. (ed.), Knobil and Neill's Physiology of Reproduction. 3rd edn, vol. 2. Academic Press, San Diego, CA, pp. 1729-1842.
16. Kalra, S.P., Dube, M.G., Pu, S., Xu, B., Horvath, T.L. & Kalra, P.S. (1999) Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr. Rev., 20, 68-100.
17. Kollack-Walker, S. & Newman, S.W. (1995) Mating and agonistic behavior produce different patterns of Fos immunolabeling in the male Syrian hamster brain. Neuroscience, 66, 721-736.
18. Kondo, Y. (1992) Lesions of the medial amygdala produce severe impairment of copulatory behavior in sexually inexperienced male rats. Physiol. Behav., 51, 939-943.
19. Kondo, Y. & Arai, Y. (1995) Functional association between the medial amygdala and the medial preoptic area in regulation of mating behavior in the male rat. Physiol. Behav., 57, 69-73.
20. Kondo, Y. & Yamanouchi, K. (1995) The possible involvement of the nonstrial pathway of the amygdala in neural control of sexual behavior in male rats. Brain Res. Bull., 38, 37-40.
21. Kruk, M.R., Westphal, K.G., Van Erp, A.M., van Asperen, J., Cave, B.J., Slater, E., de Koning, J. & Haller, J. (1998) The hypothalamus: cross-roads of endocrine and behavioural regulation in grooming and aggression. Neurosci. Biobehav. Rev., 23, 163-177.
22. Lin, D., Boyle, M.P., Dollar, P., Lee, H., Lein, E.S., Perona, P. & Anderson, D.J. (2011) Functional identification of an aggression locus in the mouse hypothalamus. Nature, 470, 221-226.
23. Lu, S.F., McKenna, S.E., Cologer-Clifford, A., Nau, E.A. & Simon, N.G. (1998) Androgen receptor in mouse brain: sex differences and similarities in autoregulation. Endocrinology, 139, 1594-1601.
24. McGinnis, M.Y., Williams, G.W. & Lumia, A.R. (1996) Inhibition of male sex behavior by androgen receptor blockade in preoptic area or hypothalamus, but not amygdala or septum. Physiol. Behav., 60, 783-789.
25. Merchenthaler, I., Lane, M.V., Numan, S. & Dellovade, T.L. (2004) Distribution of estrogen receptor alpha and beta in the mouse central nervous system: in vivo autoradiographic and immunocytochemical analyses. J. Comp. Neurol., 473, 270-291.
26. Meredith, M. (1998) Vomeronasal, olfactory, hormonal convergence in the brain. Cooperation or coincidence?. Ann. NY Acad. Sci., 855, 349-361.
27. Mitra, S.W., Hoskin, E., Yudkovitz, J., Pear, L., Wilkinson, H.A., Hayashi, S., Pfaff, D.W., Ogawa, S., Rohrer, S.P., Schaeffer, J.M., McEwen, B.S. & Alves, S.E. (2003) Immunolocalization of estrogen receptor β in the mouse brain: comparison with estrogen receptor α. Endocrinology, 144, 2055-2067.
28. Musatov, S., Chen, W., Pfaff, D.W., Kaplitt, M.G. & Ogawa, S. (2006) RNAi-mediated silencing of estrogen receptor α in the ventromedial nucleus of hypothalamus abolishes female sexual behaviors. Proc. Natl. Acad. Sci. USA, 103, 10456-10460.
29. Musatov, S., Chen, W., Pfaff, D.W., Mobbs, C.V., Yang, X.-J., Clegg, D.J., Kaplitt, M.G. & Ogawa, S. (2007) Silencing of estrogen receptor α in the ventromedial nucleus of hypothalamus leads to metabolic syndrome. Proc. Natl. Acad. Sci. USA, 104, 2501-2506.
30. Nelson, R.J. & Trainor, B.C. (2007) Neural mechanisms of aggression. Nat. Rev. Neurosci., 8, 536-546.
31. Newman, S.W. (1999) The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network. Ann. NY Acad. Sci., 877, 242-257.
32. Nomura, M., Durbak, L., Chan, J., Smithies, O., Gustafsson, J.-A., Korach, K.S., Pfaff, D.W. & Ogawa, S. (2002) Genotype/age interactions on aggressive behavior in gonadally intact estrogen receptor β knockout (βERKO) male mice. Horm. Behav., 41, 288-296.
33. Nomura, M., Andersson, S., Korach, K.S., Gustafsson, J.-A., Pfaff, D.W. & Ogawa, S. (2006) Estrogen receptor-β gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice. Eur. J. Neurosci., 23, 1860-1868.
34. Nyby, J., Matochik, J.A. & Barfield, R.J. (1992) Intracranial androgenic and estrogenic stimulation of male-typical behaviors in house mice (Mus domesticus). Horm. Behav., 26, 24-45.
35. Ogawa, S., Lubahn, D.B., Korach, K.S. & Pfaff, D.W. (1997) Behavioral effects of estrogen receptor gene disruption in male mice. Proc. Natl. Acad. Sci. USA, 94, 1476-1481.
36. Ogawa, S., Washburn, T.F., Taylor, J., Lubahn, D.B., Korach, K.S. & Pfaff, D.W. (1998) Modifications of testosterone-dependent behaviors by estrogen receptor-α gene disruption in male mice. Endocrinology, 139, 5058-5069.
37. Ogawa, S., Chan, J., Chester, A.E., Gustafsson, J.-Å., Korach, K.S. & Pfaff, D.W. (1999) Survival of reproductive behaviors in estrogen receptor β gene-deficient (βERKO) male and female mice. Proc. Natl. Acad. Sci. USA, 96, 12887-12892.
38. Ogawa, S., Chester, A.E., Hewitt, S.C., Walker, V.R., Gustafsson, J.-Å., Smithies, O., Korach, K.S. & Pfaff, D.W. (2000) Abolition of male sexual behaviors in mice lacking estrogen receptors α and β (αβERKO). Proc. Natl. Acad. Sci. USA, 97, 14737-14741.
39. Ogawa, S., Chan, J., Gustafsson, J.-Å., Korach, K.S. & Pfaff, D.W. (2003) Estrogen increases locomotor activity in mice through estrogen receptor α: specificity for the type of activity. Endocrinology, 144, 230-239.
40. Paisley, J.C., Huddleston, G.G., Carruth, L.L., Petrulis, A., Grober, M.S. & Clancy, A.N. (2012) Sexual responses of the male rat medial preoptic area and medial amygdala to estrogen I: site specific suppression of estrogen receptor alpha. Horm. Behav., 62, 50-57.
41. Paredes, R.G. (2003) Medial preoptic area/anterior hypothalamus and sexual motivation. Scand. J. Psychol., 44, 203-212.
42. Paredes, R.G., Tzschentke, T. & Nakach, N. (1998) Lesions of the medial preoptic area/anterior hypothalamus (MPOA/AH) modify partner preference in male rats. Brain Res., 813, 1-8.
43. Patil, S.N. & Brid, S.V. (2010) Relative role of neural substrates in the aggressive behavior of rats. J. Basic Clin. Physiol. Pharmacol., 21, 357-367.
44. Paxinos, G. & Franklin, K.B.J. (2001) The Mouse Brain in Stereotaxic Coordinates, 2nd edn. Academic Press, San Diego, CA, USA.
45. Petrulis, A. (2009) Neural mechanisms of individual and sexual recognition in Syrian hamsters (Mesocricetus auratus). Behav. Brain Res., 200, 260-267.
46. Putnam, S.K., Sato, S., Riolo, J.V. & Hull, E.M. (2005) Effects of testosterone metabolites on copulation, medial preoptic dopamine, and NOS-immunoreactivity in castrated male rats. Horm. Behav., 47, 513-522.
47. Russell, N.V., Ogaga-Mgbonyebi, E.V., Habteab, B., Dunigan, A.I., Tesfay, M.A. & Clancy, A.N. (2012) Sexual responses of the male rat medial preoptic area and medial amygdala to estrogen II: site specific effects of selective estrogenic drugs. Horm. Behav., 62, 58-66.
48. Sato, Y., Horita, H., Kurohata, T., Adachi, H. & Tsukamoto, T. (1998) Effect of the nitric oxide level in the medial preoptic area on male copulatory behavior in rats. Am. J. Physiol., 274, R243-R247.
49. Scordalakes, E.M. & Rissman, E.F. (2003) Aggression in male mice lacking functional estrogen receptor α. Behav. Neurosci., 117, 38-45.
50. Scordalakes, E.M., Shetty, S.J. & Rissman, E.F. (2002) Roles of estrogen receptor α and androgen receptor in the regulation of neuronal nitric oxide synthase. J. Comp. Neurol., 453, 336-344.
51. Shimura, T., Yamamoto, T. & Shimokochi, M. (1994) The medial preoptic area is involved in both sexual arousal and performance in male rats: re-evaluation of neuron activity in freely moving animals. Brain Res., 640, 215-222.
52. Shughrue, P.J., Lane, M.V. & Merchenthaler, I. (1997) Comparative distribution of estrogen receptor-α and -β mRNA in the rat central nervous system. J. Comp. Neurol., 388, 507-525.
53. Simerly, R.B., Chang, C., Muramatsu, M. & Swanson, L.W. (1990) Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J. Comp. Neurol., 294, 76-95.
54. Simon, N.G. & Whalen, R.E. (1986) Hormonal regulation of aggression: evidence for a relationship among genotype, receptor binding, and behavioral sensitivity to androgen and estrogen. Aggr. Behav., 12, 255-266.
55. Spiteri, T., Musatov, S., Ogawa, S., Ribeiro, A., Pfaff, D.W. & Ågmo, A. (2010) Estrogen-induced sexual incentive motivation, proceptivity and receptivity depend on a functional estrogen receptor α in the ventromedial nucleus of the hypothalamus but not in the amygdala. Neuroendocrinology, 91, 142-154.
56. Stowers, L. & Logan, D.W. (2010) Olfactory mechanisms of stereotyped behavior: on the scent of specialized circuits. Curr. Opin. Neurobiol., 20, 274-280.
57. Temple, J.L., Scordalakes, E.M., Bodo, C., Gustafsson, J.-Å. & Rissman, E.F. (2003) Lack of functional estrogen receptor β gene disrupts pubertal male sexual behavior. Horm. Behav., 44, 427-434.
58. Toth, M., Fuzesi, T., Halasz, J., Tulogdi, A. & Haller, J. (2010) Neural inputs of the hypothalamic "aggression area" in the rat. Behav. Brain Res., 215, 7-20.
59. Trainor, B.C., Greiwe, K.M. & Nelson, R.J. (2006) Individual differences in estrogen receptor alpha in select brain nuclei are associated with individual differences in aggression. Horm. Behav., 50, 338-345.
60. Veening, J.G., Coolen, L.M., de Jong, T.R., Joosten, H.W., de Boer, S.F., Koolhaas, J.M. & Olivier, B. (2005) Do similar neural systems subserve aggressive and sexual behaviour in male rats? Insights from c-Fos and pharmacological studies Eur. J. Pharmacol., 526, 226-239.
61. Wersinger, S.R. & Rissman, E.F. (2000) Oestrogen receptor α is essential for female-directed chemo-investigatory behaviour but is not required for the pheromone-induced luteinizing hormone surge in male mice. J. Neuroendocrinol., 12, 103-110.
62. Wood, R.I. (1996) Functions of the steroid-responsive neural network in the control of male hamster sexual behavior. Trends Endocrinol. Metab., 7, 338-344.
63. Wood, R.I. & Newman, S.W. (1995) The medial amygdaloid nucleus and medial preoptic area mediate steroidal control of sexual behavior in the male Syrian hamster. Horm. Behav., 29, 338-353.
64. Yeh, K.-Y., Pu, H.-F., Wu, C.-H., Tai, M.-Y. & Tsai, Y.-F. (2009) Different subregions of the medial preoptic area are separately involved in the regulation of copulation and sexual incentive motivation in male rats: a behavioral and morphological study. Behav. Brain Res., 205, 219-225.
65. Yoon, H., Enquist, L.W. & Dulac, C. (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell, 123, 669-682.