Maladaptive Alterations of Defensive Response Following Developmental Complex Stress in Rats

Abstract

Objective Despite the etiological significance of complex developmental trauma in adult personality disorders and treatment-resistant depression, neurobiological studies have been rare due to the lack of useful animal models. As a first step, we devised an animal model to investigate the effects of multiple trauma-like stress during different developmental periods. Methods Twenty-one male Sprague-Dawley rats were classified into 3 groups based on the stress protocol: fear conditioning control (FCC, n = 6), complex stress (ComS, n = 9), and control (n = 6). While the ComS experienced three types of stress (maternal separation, juvenile isolation, electric foot shock), the FCC only experienced an electric foot shock stress and the control never experienced any. We compared fear responses at postnatal day (PND) 29 and PND 56 through freezing time per episode (FTpE), total freezing time (TFT), total freezing episodes (TFE), and ultrasonic vocalization (USV). Results ComS showed the longest FTpE in the conditioned fear response test. ComS and FCC exhibited the longer TFT and these two groups only displayed USV. ComS show difference TFE between PND 29 and PND 56. Conclusion The results of this investigation show that complex stress may affect not quantity of fear response but characteristics of fear response. Longer FTpE may be associated with tonic immobility which could be considered as a failed self-protective reaction and might be analogous to a sign of inappropriate coping strategy and self-dysregulation in complex trauma patients.

Effects of Maternal Separation and Subsequent Stress on Behaviors and Brain Monoamines in Rats

“…According to the “double hit” hypothesis, early postnatal stress modulates the resilience/sensitivity of adult animals to stressful stimuli by modulating (among other mechanisms) activity of the brain neurotransmitter systems [ 30 ]. Recent studies have demonstrated that complex stress that included maternal separation in the early postnatal period, isolation during adolescence, and inescapable foot shock led to the appearance of more numerous and longer freezing episodes (tonic immobility) in the fear conditioning test in 2-month-old male rats in comparison with animals subjected to foot-shock stress alone and native controls [ 112 ]. This behavioral pattern can be associated with the inability of individuals exposed to early stress to integrate information and to respond appropriately to environmental stimuli.…”