The effect of chronic stress on the adolescent brain, learning, and memory

Abstract

Adolescence is a period in which major psychological and neural changes occur, along with changes in the stress response. This has resulted in some researchers characterising this developmental period as one of “storm and stress”. Interestingly, the brain regions implicated in learning and memory processes are both particularly sensitive to stress and undergoing major development during adolescence. Therefore, the broad aim of this thesis was to examine the impact of chronic stress exposure early in life on learning and memory processes that underlie a number of mental disorders. In the first two empirical Chapters, I examined pharmacological and endogenous activation of Tropomyosin receptor kinase B (TrkB), a key mediator of activity-dependent plasticity underlying memory, during Pavlovian fear conditioning and extinction in adolescent rats. In Chapter 2 I examined the effects of an agonist of TrkB on extinction retention in both non-stressed adolescent rodents and those that had been exposed to chronic levels of corticosterone, a stress-related hormone. Pharmacological activation of TrkB during extinction training facilitated extinction retention in non-stressed adolescent rats, but not in those exposed to chronic corticosterone. In Chapter 3 I examined levels of full-length, truncated, and activated (phosphorylated) TrkB receptors in three key brain regions involved in extinction: the ventral hippocampus, prefrontal cortex, and basolateral amygdala, of adult and adolescent rats following extinction training. One pertinent finding of this work was a significantly higher ratio of truncated to full-length TrkB receptors in the ventral hippocampus of adults than adolescents. In Chapter 4 human participants (older adolescents and adults) were exposed to an acute stressor (the cold pressor test) prior to viewing trauma images and provided salivary samples for analyses of the stress hormone cortisol. Participants recorded instances of intrusive, involuntary memories of these images over subsequent days. No age differences were detected in relation to the number of intrusive memories reported by participants, or their cortisol response to the cold pressor test. However, individuals with higher levels of early-life adversity were significantly more affected by exposure to trauma images. Taken together, these experiments extend knowledge of the impact of chronic stress and adversity in adolescence on learning and memory.