Adolescence is associated with the emergence of several sex-biased mental illnesses, including eating, mood, and conduct disorders and schizophrenia. Each of these psychopathologies involves impairments in social information processing and social proficiency, which together comprise the ability to recognize, perceive, and interpret socially-relevant information and to apply it appropriately in specific social contexts. A fundamental but unanswered question about normal adolescent development is which of these two aspects of adolescent maturation are governed by pubertal gonadal hormones and which are not, and what neural mechanisms underlie hormone-dependent and -independent remodeling of social behavior circuits. The proposed research uses a well-suited laboratory rodent model, the male Syrian hamster, to empirically test the hypothesis that the adolescent transition in social information processing is gonadal hormone-independent, while adolescent maturation of social proficiency is gonadal hormone-dependent. Using a conditioned place preference paradigm and experimental manipulation of social experience, Aim 1 will test the hypothesis that adolescent changes in social information processing are governed by hormone-independent developmental processes that alter the rewarding properties of social stimuli, whereas adolescent maturation of social proficiency, the ability to make behavioral adaptations in response to social experience, is programmed by testicular hormones during puberty.
Aim 2 will characterize neural activation patterns in response to female sensory stimuli, as indexed by fos expression, to determine how neural responses to social stimuli are altered by the presence or absence of testicular hormones during adolescent development. Using the cell birth-date marker bromo-deoxy-uridine in combination with markers of cell function and pharmacological inhibition of brain cytogenesis, Aim 3 will investigate whether the pubertal addition of new cells to social behavior circuits is a mechanism by which gonadal hormones organize the adolescent brain. This research will establish an understanding of hormone-dependent and hormone-independent components of the adolescent maturation of social behaviors, and will investigate a novel mechanism by which gonadal hormones organize and remodel the adolescent brain. The identification of specific aspects of normal adolescent development that are hormone-dependent versus hormone-independent will advance understanding of the role that pubertal hormones play in the etiology of sex-biased mental illnesses associated with adolescence, and will facilitate the development of more effective strategies for prevention and treatment of these disorders.

Public Health Relevance

This research project will investigate how gonadal hormones shape the structure and function of adolescent brain to influence the maturation of social behavior. The work will contribute to an understanding of the role of pubertal hormones in the etiology of sex-biased mental illnesses that involve impairments in social cognition, such as eating and mood disorders and schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1-IFCN-H (03))
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Simmons, Janine M
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Michigan State University
Schools of Arts and Sciences
East Lansing
United States
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Bell, Margaret R; Meerts, Sarah H; Sisk, Cheryl L (2013) Adolescent brain maturation is necessary for adult-typical mesocorticolimbic responses to a rewarding social cue. Dev Neurobiol 73:856-69
De Lorme, Kayla C; Sisk, Cheryl L (2013) Pubertal testosterone programs context-appropriate agonistic behavior and associated neural activation patterns in male Syrian hamsters. Physiol Behav 112-113:1-7
Mohr, Margaret A; Sisk, Cheryl L (2013) Pubertally born neurons and glia are functionally integrated into limbic and hypothalamic circuits of the male Syrian hamster. Proc Natl Acad Sci U S A 110:4792-7
Bell, Margaret R; De Lorme, Kayla C; Figueira, Rayson J et al. (2013) Adolescent gain in positive valence of a socially relevant stimulus: engagement of the mesocorticolimbic reward circuitry. Eur J Neurosci 37:457-68
Bell, Margaret R; Sisk, Cheryl L (2013) Dopamine mediates testosterone-induced social reward in male Syrian hamsters. Endocrinology 154:1225-34
Bell, Margaret R; Meerts, Sarah H; Sisk, Cheryl L (2010) Male Syrian hamsters demonstrate a conditioned place preference for sexual behavior and female chemosensory stimuli. Horm Behav 58:410-4
Salas-Ramirez, Kaliris Y; Montalto, Pamela R; Sisk, Cheryl L (2010) Anabolic steroids have long-lasting effects on male social behaviors. Behav Brain Res 208:328-35
Schulz, Kalynn M; Zehr, Julia L; Salas-Ramirez, Kaliris Y et al. (2009) Testosterone programs adult social behavior before and during, but not after, adolescence. Endocrinology 150:3690-8
Schulz, Kalynn M; Molenda-Figueira, Heather A; Sisk, Cheryl L (2009) Back to the future: The organizational-activational hypothesis adapted to puberty and adolescence. Horm Behav 55:597-604
Sato, Satoru M; Schulz, Kalynn M; Sisk, Cheryl L et al. (2008) Adolescents and androgens, receptors and rewards. Horm Behav 53:647-58

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