Dissertation/Thesis Abstract

Long-term consequences of adolescent social defeat on cognition and prefrontal cortex dopamine function
by Novick, Andrew Michael, Ph.D., University of South Dakota, 2015, 196; 3714207
Abstract (Summary)

Individuals who are victimized by bullying during adolescence demonstrate an increased incidence of psychiatric disorders both acutely and later in life. Many of these disorders are characterized by deficits in complex cognitive functions that are mediated by the mesocortical dopamine system. The substantial maturation of the mesocortical dopamine system during adolescence may render it particularly vulnerable to insult from psychosocial stressors such as bullying. Using a rodent model of adolescent social defeat to replicate the imbalance of power inherent in teenage bullying, it was previously demonstrated that defeated rats exhibit various behavioral and neurochemical indications of mesocortical dopamine hypofunction in adulthood. The experimental chapters of this dissertation aim to further understand the consequences of victimization stress during adolescence by 1) evaluating the effects of adolescent social defeat on dopamine dependent cognitive processes and 2) investigating the potential mechanisms by which adolescent social defeat results in mesocortical dopamine hypofunction. Adult rats defeated in adolescence and their controls were initially tested on two separate tasks of working memory known to be dependent on mesocortical dopamine activity, the delayed alternating T-maze task and the delayed win-shift task. Results found a direct link between adolescent social defeat and adult working memory deficits, with previously defeated rats demonstrating impaired performance in the maintenance and utilization of information following delays of 90 seconds and 5 minutes on the T-maze and win-shift tasks respectively. In a separate experiment, quantitative autoradiography revealed increased expression of the dopamine transporter (DAT) in the infralimbic region of the medial prefrontal cortex (mPFC) of adult rats defeated in adolescence. Further investigation of mPFC DAT function utilizing in vivo chronoamperometry demonstrated that previously defeated rats exhibit decreased dopamine accumulation in response to pharmacological DAT inhibition, indicating enhanced DAT function that may increase clearance of dopamine in the mPFC. Combined, these results suggest that increased functional expression of DAT in the mPFC following adolescent social defeat leads to enhanced clearance of dopamine, contributing to deficits in mPFC dopamine activity and associated cognitive processes. Having identified a putative mechanism by which adolescent social defeat causes mesocortical dopamine hypofunction, the results of these experiments can assist in directing the clinical application of novel and existing pharmacotherapies to counteract the deleterious effects of adolescent stress.

Indexing (document details)
Advisor: Watt, Michael J.
Commitee: Forster, Gina L., Kost, Curtis K., Lindahl, Josette S., Waller, Steve B.
School: University of South Dakota
Department: Basic Biomedical Sciences
School Location: United States -- South Dakota
Source: DAI-B 76/12(E), Dissertation Abstracts International
Subjects: Neurosciences, Psychobiology, Behavioral psychology
Keywords: Adolesence, Bullying, Dopamine, Prefrontal cortex, Stress
Publication Number: 3714207
ISBN: 978-1-321-91338-5
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