A unique profile of fear conditioning and extinction in adolescent rats and humans

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Copyright: Den, Miriam
Translational research on fear conditioning and extinction has led to undeniable gains in our understanding of anxiety disorders. However, the majority of these studies have been conducted in adults, with little known about these processes in adolescence. A “one size fits all” approach to understanding and treating anxiety is inappropriate given the neural structures mediating conditioning and extinction are reorganised in adolescence. These changes render the adolescent brain vulnerable to environmental disruptions, partly explaining why most anxiety disorders emerge at this time. Thus, my thesis investigated fear conditioning and extinction in adolescent rats and humans. In my first series of experiments (Chapter 2), adolescent rats showed greater fear expression relative to juveniles and adults 24 hours after trace conditioning (i.e., a stimulus-free interval between the CS and US). Exposure to the stress hormone corticosterone (CORT) via the drinking water for 7 days impaired trace conditioning in adolescents. These experiments provide strong evidence that adolescents are more likely to learn fear associations, and this is disrupted following exposure to CORT. The second series of experiments (Chapter 3) examined whether CORT exacerbates extinction retention deficits in adolescent rats. One week of CORT in the drinking water disrupted short- and long-term extinction retention in adolescence, but 3 weeks of CORT was necessary for these disruptions to be observed in adults. Greater vulnerability to the disruptive effects of CORT in adolescence may be due to the maturation of stress-sensitive brain regions. Chapter 4 of my thesis compared fear conditioning, extinction, and reinstatement in adolescent and adult humans. Adolescents showed stronger conditioning than adults on self-report ratings and eye tracking measures. On the self-report measures, both age groups showed good extinction learning and retention, as well as reinstatement-induced relapse, yet only adolescents showed conditioning and extinction on the eye tracking measures. Reinstatement in adolescents was only observed on one of the eye tracking measures but could not be measured in adults given they did not show initial conditioning or extinction on these measures. Higher levels of depression predicted stronger conditioning and weaker extinction in adolescents only. These findings are discussed in terms of broader implications for translational research on anxiety in adolescence.
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Den, Miriam
Richardson, Rick
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PhD Doctorate
UNSW Faculty
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