Long Term Effects of Chronic Variable Stress Administered during Different Developmental Stages in Mice
Abstract
A number of studies have suggested that the occurrence of past trauma can increase an individual's chance of developing PTSD from a new traumatic experience later in life. Trauma that occurs during childhood appears to have a particularly strong effect on this risk increase. Furthermore, conditioned fear responses have been shown to incubate over extended periods of time in animal models. To further investigate the role these phenomena play in the development of PTSD, this study exposed juvenile and adult mice to 7 days of chronic variable stress (CVS). One month later, a Pavlovian delay fear conditioning procedure was used to assess fear learning behavior, and anxiety levels were assessed with an Elevated Plus-Maze (EPM). It was hypothesized that mice who experienced CVS exposure as juveniles would show greater long-term levels of anxiety and long-term sensitization to later fear learning than mice who experienced CVS as adults. Furthermore, mice exposed to CVS, regardless of age, were hypothesized to show significantly enhanced anxiety and fear conditioning relative to control mice. Surprisingly, it was found that stress induced sensitization of fear conditioning deteriorated over the 30-day incubation period for both juvenile and adult mice, leading to no differences between groups, including controls, in fear learning behaviors. Adult stressed mice showed significantly greater anxiety levels than adult controls, while juvenile stressed and control mice showed no difference in anxiety. These results suggest possible neurological differences between juvenile and adult mice in regions involved in fear learning, such as the hippocampus, the central nucleus of the amygdale, and the bed nucleus of the stria terminalis. Alternative interpretations of the data are discussed. Despite failing to support the proposed hypotheses, this study suggests that a successful animal model of PTSD should consider the differential dynamics of associative and non-associative fear learning processes. Furthermore, the moderating effects of developmental stages on the effects of chronic stress should also be acknowledged and investigated further.