During human adolescence the brain undergoes a profound remodeling that is both sculpted by gonadal steroid hormones and associated with the emergence of sex-biased psychopathologics such as anorexia nervosa, depression, and schizophrenia. Because puberty is a period of extraordinarily rapid change in the nervous system, the brain may be particularly vulnerable to perturbations in the timing of interactions between hormones and developmental trajectory. The normal timing of these interactions in human adolescents is altered by anabolic steroid use, by the increasingly earlier onset of gonadal puberty in girls, and by the delay in gonadal maturation induced by eating disorders, extreme exercise, or disease. The overall goal of this research is to determine how the timing of interactions between the rapidly developing adolescent brain and gonadal steroid hormones influences individual differences adult behavior and nervous system structure. Using a rodent model, we've found that the absence of gonadal hormones during pubertal brain development adversely affects the expression of male social behaviors in adulthood. These behavioral compromises are long-lasting, and are not reversed by testosterone replacement in adulthood, indicating that the timing of exposure to steroid hormones determines adult responses to hormonal and sensory stimuli.
The specific aims of the proposed work are to 1) test the hypothesis that capacity for testosterone-dependent organization of reproductive behavior varies over prepubertal, pubertal, and postpubertal development; 2) discover whether androgenic or estrogenic actions of testosterone mediate testosterone-dependent organization of neural circuits and behavior during puberty; and 3) test the hypothesis that steroid-dependent pubertal organization of male reproductive behavior is associated with enduring structural modifications within the neural circuit mediating the behavior. The strategy will be to vary the postnatal age at which male hamsters are exposed to a three week period of androgen or estrogen (either before, during, or after puberty), and then assess behavior and structural characteristics in adulthood. This research integrates neuroanatomy, endocrinology, and behavior, and will establish new and fundamental principles of developmental neurobiology and psychobiology that are directly relevant to human development and mental health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH068764-01A1
Application #
6776585
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Quinn, Kevin J
Project Start
2004-04-01
Project End
2009-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
1
Fiscal Year
2004
Total Cost
$336,375
Indirect Cost
Name
Michigan State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Molenda-Figueira, Heather A; Bell, Margaret R; De Lorme, Kayla C et al. (2017) Pubertal pair-housing facilitates adult sexual behavior in male rats. Dev Psychobiol 59:111-117
Walker, Deena M; Bell, Margaret R; Flores, Cecilia et al. (2017) Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos. J Neurosci 37:10855-10866
Schulz, Kalynn M; Sisk, Cheryl L (2016) The organizing actions of adolescent gonadal steroid hormones on brain and behavioral development. Neurosci Biobehav Rev 70:148-158
Sisk, Cheryl L (2016) Hormone-dependent adolescent organization of socio-sexual behaviors in mammals. Curr Opin Neurobiol 38:63-8
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
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
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
De Lorme, Kayla; Bell, Margaret R; Sisk, Cheryl L (2013) The Teenage Brain: Social Reorientation and the Adolescent Brain-The Role of Gonadal Hormones in the Male Syrian Hamster. Curr Dir Psychol Sci 22:128-133
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
Bell, Margaret R; Sisk, Cheryl L (2013) Dopamine mediates testosterone-induced social reward in male Syrian hamsters. Endocrinology 154:1225-34

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