This grant aims to understand the function of sex differences in developing brains by focusing on the higher level of vasopressin expression in male versus female brains. This is the most consistently found sex difference among vertebrates, and the best understood in terms of function in adult animals. Interestingly, this sex difference is even more dramatic in juveniles (almost absolute), yet no attempts have been made to study its function at this stage. This grant will study whether the sex difference in vasopressin innervation contributes to sex differences in the display and control of social behavior in juvenile rats. The focus will be on social play (or play fighting), a behavior that is much more pronounced in males than in females and probably the first social behavior that is not directed at the mother.
The first aim i s to paint a comprehensive picture of vasopressin development by monitoring vasopressin mRNA levels, peptide distribution, and receptor binding in the developing brain. This is essential for generating hypotheses as to how vasopressin may contribute to sex differences in social behavior.
The second aim i s to test whether social play is accompanied by changes in central vasopressin release.
The third aim i s to test the hypothesis that central vasopressin release contributes to sex differences in the emergence and control of social behavior by testing the effects of vasopressin or vasopressin receptor antagonists on social play and social recognition. Understanding how the brain controls social behavior during development is important as many behavioral disorders show striking sex differences in morbidity that manifest themselves during development. For example, autism spectrum disorders (ASD) are much more common in boys than in girls. Sexual differentiation of the brain likely contributes to these differences. Although recently major advances have been made in understanding the neural basis of social behavior in adulthood, how such behavior is controlled during development is by and large unknown. This grant will address these issues.

Public Health Relevance

Behavioral disorders that manifest themselves during development, such as autism spectrum disorders, are often more common and severe in boys than in girls. Sexual differentiation of the brain likely contributes to these differences. This research explores the behavioral consequences of neural sex differences in juvenile rats.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
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Simmons, Janine M
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Georgia State University
Schools of Arts and Sciences
United States
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Veenema, Alexa H; Bredewold, Remco; De Vries, Geert J (2013) Sex-specific modulation of juvenile social play by vasopressin. Psychoneuroendocrinology 38:2554-61
Veenema, A H; Bredewold, R; De Vries, G J (2012) Vasopressin regulates social recognition in juvenile and adult rats of both sexes, but in sex- and age-specific ways. Horm Behav 61:50-6
Rood, Benjamin D; De Vries, Geert J (2011) Vasopressin innervation of the mouse (Mus musculus) brain and spinal cord. J Comp Neurol 519:2434-74
McCarthy, Margaret M; Auger, Anthony P; Bale, Tracy L et al. (2009) The epigenetics of sex differences in the brain. J Neurosci 29:12815-23
de Vries, Geert J; Sodersten, Per (2009) Sex differences in the brain: the relation between structure and function. Horm Behav 55:589-96
Murray, Elaine K; Hien, Annie; de Vries, Geert J et al. (2009) Epigenetic control of sexual differentiation of the bed nucleus of the stria terminalis. Endocrinology 150:4241-7
de Vries, Geert J; Jardon, Michelle; Reza, Mohammed et al. (2008) Sexual differentiation of vasopressin innervation of the brain: cell death versus phenotypic differentiation. Endocrinology 149:4632-7
Rood, B D; Murray, E K; Laroche, J et al. (2008) Absence of progestin receptors alters distribution of vasopressin fibers but not sexual differentiation of vasopressin system in mice. Neuroscience 154:911-21
Molenda-Figueira, Heather A; Murphy, Suzanne D; Shea, Katherine L et al. (2008) Steroid receptor coactivator-1 from brain physically interacts differentially with steroid receptor subtypes. Endocrinology 149:5272-9
de Vries, Geert J (2008) Sex differences in vasopressin and oxytocin innervation of the brain. Prog Brain Res 170:17-27

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