Abstract
Epidemiological evidence identifies early life adversity as a significant risk factor for the development of mood disorders. Much evidence points to the role of early life experience in susceptibility and, to a lesser extent, resilience, to stress in adulthood. While many models of these phenomena exist in the literature, results are often conflicting and a systematic comparison of multiple models is lacking. Here, we compare effects of nine manipulations spanning the early postnatal through peri-adolescent periods, both at baseline and following exposure to chronic social defeat stress in adulthood, in male mice. By applying rigorous criteria across three commonly used measures of depression- and anxiety-like behavior, we identify manipulations that increase susceptibility to subsequent stress in adulthood and other pro-resilient manipulations that mitigate the deleterious consequences of adult stress. Our findings point to the importance of timing of early life stress and provide the foundation for future studies to probe the neurobiological mechanisms of risk and resilience conferred by variation in the early life environment.
Highlights
In the past decade, the chronic social defeat stress (CSDS) paradigm has emerged as one of the most robust and consistent mouse models for depression-like behavioral abnormalities (Berton et al, 2006; Laman-Maharg and Trainor, 2017; Slattery and Cryan, 2017)
We systematically examined the delayed effect of nine environmental manipulations, spanning the early postnatal, late postnatal, and peri-adolescent periods, in altering responses to CSDS in adulthood
Susceptibility and resilience were assessed by a battery of three widely used tests of depression- and anxiety-like behavior with all experiments conducted under comparable conditions in the same animal facility to facilitate direct comparison across manipulations, eliminating a source of variation that has confounded efforts to synthesize effects of early life manipulations among published studies
Summary
The chronic social defeat stress (CSDS) paradigm has emerged as one of the most robust and consistent mouse models for depression-like behavioral abnormalities (Berton et al, 2006; Laman-Maharg and Trainor, 2017; Slattery and Cryan, 2017). We set out to establish a mouse “two-hit” model wherein specific early life experience increases susceptibility to depression-like behavior after social defeat in adulthood, and a contrasting model in which different early life experience promotes resilience to the same social defeat in adulthood. Several models of early life adversity, “stress inoculation,” and environmental enrichment have reported baseline changes in anxiety- or depression-like behavior in adulthood, without considering the consequences of exposure to further stress in adulthood. A model that failed to meet all three of these three criteria was considered to promote resilience (i.e., behavior was not modified at baseline nor by defeat), as were manipulations that met criterion 3 by significantly changing behavior in a direction opposing defeat-induced change in standard-reared mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
