Effects of Unpredictable Chronic Mild Stress on Adolescent Rats

[摘要] Adolescence is a period of many behavioral, physiological, and neural changes, and has been considered to be a period of vulnerability to neuropsychiatric disorders. Individual differences in early life experiences or response strategies may be able to identify those most at risk and, conversely, most resistant to the development of neuropsychiatric disorders such as depression, anxiety, and addiction. Although much is known about the effects of early life stress on adult outcomes, a critical missing piece of information in the field is what the effects of chronic stress during adolescence are in adolescence. Unpredictable chronic mild stress (UCMS) is a widely-used model for inducing depressive- and anxiety-like behaviors in adult rodents that has also been shown to have differential outcome based on individual differences in novelty-seeking. This thesis investigates the immediate behavioral, neuroendocrine, and neurobiological effects of UCMS during adolescence, to fill a critical void in the current literature on adolescent stress exposure. It also examines whether individual differences in adolescents are associated with differential consequences of unpredictable stress during adolescence. I show that UCMS during adolescence does not induce a depressive- or anxiety-like phenotype, but instead evokes hyperactivity and decreased anxiety, and that peri-weaning experience can modulate the effect of UCMS. Further, we show that a response strategy strongly predictive of susceptibility/resistance to depression in adult rats — locomotor activity in a novel environment — is not yet a stable response attribute in adolescent rats and consequently not a valuable predictive tool. Taken together, our work suggests that adolescents may be resistant to depressive- and anxiety-like consequences induced by chronic mild stress, and that stronger stressors may be required to induce a depressive-like phenotype in adolescence. In light of some evidence showing that UCMS during adolescence produces a depressive phenotype in adulthood, our work suggests that post-adolescent processes play a role in the development of the adult outcome.

[发布机构] the University of Pittsburgh