Estrogen Receptors in the Medial Amygdala Inhibit the Expression of Male Prosocial Behavior

Overview

Journal J Neurosci

Specialty Neurology

Date 2008 Oct 10

PMID 18842899

Citations 43

Authors

Bruce S Cushing

Adam Perry

Sergei Musatov

Sonoko Ogawa

Eros Papademetriou

Affiliations

Soon will be listed here.

Abstract

Studies using estrogen receptor alpha (ERalpha) knock-out mice indicate that ERalpha masculinizes male behavior. Recent studies of ERalpha and male prosocial behavior have shown an inverse relationship between ERalpha expression in regions of the brain that regulate social behavior, including the medial amygdala (MeA), and the expression of male prosocial behavior. These studies have lead to the hypothesis that low levels of ERalpha are necessary to "permit" the expression of high levels of male prosocial behavior. To test this, viral vectors were used to enhance ERalpha in male prairie voles (Microtus ochrogaster), which display high levels of prosocial behavior and low levels of MeA ERalpha. Adult male prairie voles were transfected with ERalpha in the MeA (MeA-ERalpha) or the caudate-putamen (ERalpha control) or luciferase (MeA-site-specific control), and 3 weeks later tested for spontaneous alloparental behavior and partner preference. Enhancing ERalpha in the MeA altered/reduced male prosocial behavior. Only one-third of MeA-ERalpha males, compared with all control males, were alloparental. MeA-ERalpha males also displayed a significant preference for a novel female. This is a critical finding because the manipulations of neuropeptides, oxytocin and vasopressin, can inhibit the formation of a partner preference, but do not lead to the formation of a preference for a novel female. The results support the hypothesis that low levels of ERalpha are necessary for high levels of male prosocial behavior, and provide the first direct evidence that site-specific ERalpha expression plays a critical role in the expression of male prosocial behavior.

Citing Articles

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References

Clark K, Liu X, McGrath J, Johnson P . Highly purified recombinant adeno-associated virus vectors are biologically active and free of detectable helper and wild-type viruses. Hum Gene Ther. 1999; 10(6):1031-9. DOI: 10.1089/10430349950018427. View

Newman S . The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network. Ann N Y Acad Sci. 1999; 877:242-57. DOI: 10.1111/j.1749-6632.1999.tb09271.x. View

Young L, Nilsen R, Waymire K, Macgregor G, Insel T . Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature. 1999; 400(6746):766-8. DOI: 10.1038/23475. View

Cho M, Devries A, Williams J, Carter C . The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav Neurosci. 1999; 113(5):1071-9. DOI: 10.1037//0735-7044.113.5.1071. View

Insel T, Young L . The neurobiology of attachment. Nat Rev Neurosci. 2001; 2(2):129-36. DOI: 10.1038/35053579. View

Liu Y, Curtis J, Wang Z . Vasopressin in the lateral septum regulates pair bond formation in male prairie voles (Microtus ochrogaster). Behav Neurosci. 2001; 115(4):910-9. DOI: 10.1037//0735-7044.115.4.910. View

Sheehan T, Paul M, Amaral E, Numan M, Numan M . Evidence that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei to inhibit maternal behavior in rats. Neuroscience. 2001; 106(2):341-56. DOI: 10.1016/s0306-4522(01)00286-x. View

FERGUSON J, Aldag J, Insel T, Young L . Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci. 2001; 21(20):8278-85. PMC: 6763861. View

Krezel W, Dupont S, Krust A, Chambon P, Chapman P . Increased anxiety and synaptic plasticity in estrogen receptor beta -deficient mice. Proc Natl Acad Sci U S A. 2001; 98(21):12278-82. PMC: 59805. DOI: 10.1073/pnas.221451898. View

10.

Lonstein J, Rood B, de Vries G . Parental responsiveness is feminized after neonatal castration in virgin male prairie voles, but is not masculinized by perinatal testosterone in virgin females. Horm Behav. 2002; 41(1):80-7. DOI: 10.1006/hbeh.2001.1740. View

11.

Cushing B, Okorie U, Young L . The effects of neonatal castration on the subsequent behavioural response to centrally administered arginine vasopressin and the expression of V1a receptors in adult male prairie voles. J Neuroendocrinol. 2003; 15(11):1021-6. DOI: 10.1046/j.1365-2826.2003.01097.x. View

12.

Hammock E, Young L . Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol Biol Evol. 2004; 21(6):1057-63. DOI: 10.1093/molbev/msh104. View

13.

Cushing B, Razzoli M, Murphy A, Epperson P, Le W, Hoffman G . Intraspecific variation in estrogen receptor alpha and the expression of male sociosexual behavior in two populations of prairie voles. Brain Res. 2004; 1016(2):247-54. DOI: 10.1016/j.brainres.2004.05.010. View

14.

Moy S, Nadler J, Perez A, Barbaro R, Johns J, Magnuson T . Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice. Genes Brain Behav. 2004; 3(5):287-302. DOI: 10.1111/j.1601-1848.2004.00076.x. View

15.

Young L, Wang Z . The neurobiology of pair bonding. Nat Neurosci. 2004; 7(10):1048-54. DOI: 10.1038/nn1327. View

16.

Keverne E, Curley J . Vasopressin, oxytocin and social behaviour. Curr Opin Neurobiol. 2004; 14(6):777-83. DOI: 10.1016/j.conb.2004.10.006. View

17.

Kudwa A, Bodo C, Gustafsson J, Rissman E . A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior. Proc Natl Acad Sci U S A. 2005; 102(12):4608-12. PMC: 555526. DOI: 10.1073/pnas.0500752102. View

18.

Hammock E, Lim M, Nair H, Young L . Association of vasopressin 1a receptor levels with a regulatory microsatellite and behavior. Genes Brain Behav. 2005; 4(5):289-301. DOI: 10.1111/j.1601-183X.2005.00119.x. View

19.

Cushing B, Kramer K . Mechanisms underlying epigenetic effects of early social experience: the role of neuropeptides and steroids. Neurosci Biobehav Rev. 2005; 29(7):1089-105. DOI: 10.1016/j.neubiorev.2005.04.001. View

20.

Young L, Murphy Young A, Hammock E . Anatomy and neurochemistry of the pair bond. J Comp Neurol. 2005; 493(1):51-7. DOI: 10.1002/cne.20771. View