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Early life experiences play a major role in adult onset psychopathology. Childhood maltreatment, whether physical or emotional, is linked to mental illness and behavioral malfunctioning. Individuals who are emotionally, physically, or sexually abused as children have a higher prevalence of major depression, drug abuse, and suicide. Most current animal models are unable to tease apart the potentially distinct effects of emotional versus physical stress, and they focus mainly on stress effects in pre-weanling or adult animals and often overlook adolescence, a critical developmental period. Therefore, the following set of experiments was designed to examine the life-long effects of physical (PS) and emotional (ES) stress using a novel model of stress during adolescence. In this study, adolescent male C57BL/6J mice were divided into three groups: those experiencing social defeat, those forced to witness the social defeat, and no stress controls. Briefly, the home cage of a male CD-1 retired breeder mouse was separated by a Plexiglas divider into two adjacent compartments. An adolescent male C57BL/6J mouse was introduced into the compartment territorialized by the CD-1 mouse where it was repeatedly overpowered (PS), demonstrating escape-like behaviors, vocalizations, and submissive posturing, while a second adolescent male C57BL/6J mouse witnessed (ES) this interaction from the adjacent compartment. Here it is demonstrated that 10 days of PS or ES exposure during adolescence (PD 35-44) induces long-lasting deficits in a battery of behavioral assays designed to assess changes in mood in adulthood. Specifically, exposure to PS or ES increases anxiety- and depression-like behaviors as measured by the elevated plus maze and forced swim test. Interestingly, mice exposed to PS and ES also displayed social avoidance in the social interaction test. Molecular analyses yielded reduced expression of the scaffolding protein shank3 within the ventral tegmental area (VTA), a brain region highly implicated in responses to stress and the etiology of mood disorders, in both ES- and PS-exposed mice. Overexpressing shank3 within the VTA was sufficient to restore control levels of social interaction in both PS- and ES-exposed mice. Together, these data indicate that experiencing traumatic stress, whether physical or emotional, is a potent stressor in adolescent mice capable of inducing life-long behavioral dysregulation, and changes in shank3 expression may mediate some of these effects.
A Dissertation submitted to the Department of Psychology in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Includes bibliographical references.
Carlos A. Bolaños-Guzmán, Professor Directing Dissertation; Branko Stefanovic, University Representative; Zuoxin Wang, Committee Member; Mohamed Kabbaj, Committee Member; Jesse Cougle, Committee Member.
Florida State University
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