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Long-Lasting Sex-Specific Effects Based On Emotion- and Cognition-Related Behavioral Assessment of Adult Rats After Post-Traumatic Stress Disorder From Different Lengths of Maternal Separation.

ABSTRACT: Adverse early life stress is a major cause of vulnerability to various mental disorders in adulthood, including post-traumatic stress disorder (PTSD). Recent studies have suggested that early life stress can help the body adapt optimally when faced with stressful trauma in adult life. An interaction may exist between early life stress (e.g., childhood trauma) and vulnerability to PTSD. This study aimed to evaluate emotion-related behaviors and verify the long-lasting effects of cognitive aspects of PTSD after exposure to severe adverse early life stress, such as long-term separation. Adverse early life stress was simulated by subjecting rats to 3 or 6 consecutive hours of maternal separation (MS) daily, from postnatal day (PND) 2 to PND 14. Single-prolonged stress (SPS) was simulated on PND 80 to imitate other adulthood stresses of PTSD with gender divisions (M-MS3h-PTSD, F-MS3h-PTSD, M-MS6h-PTSD, F-MS6h-PTSD, M-PTSD, and F-PTSD). After the MS and PTSD sessions, behavioral tests were conducted to assess the effectiveness of these treatments, which included an open field test (OFT), elevated plus maze test (EPMT), water maze test (WMT), and forced swimming test (FST) to detect anxiety-like behavior (OFT and EPMT), memory behavior (WMT), and depressive behavior (FST). The M-MS3h-PTSD group had fewer time entries into the open arms of EPMT than the F-MS3h-PTSD group, and the M-MS6h-PTSD group demonstrated fewer up-right postures in the OFT than the F-MS6h-PTSD group. The M-MS3h-PTSD group exhibited more exploratory behavior than the M-MS6h-PTSD and M-PTSD groups in the OFT. Less exploratory behavior was observed in the F-MS3h-PTSD group than in the F-MS6h-PTSD group, which demonstrated significantly increased freezing times in the FST compared to the F-PTSD group. The WMT revealed significant differences in learning and memory performance between the M-MS3h-PTSD group and other treatment groups, which were not found in the female rats. These findings demonstrate that an early stressful experience, such as MS, may be involved in helping the body adapt optimally when faced with additional trauma in adulthood, although mild early life stress might benefit learning and memory among males.

SUBMITTER: Yang R

PROVIDER: S-EPMC6558979 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Maternal separation (MS) stress is known to induce long-lasting alterations in emotional and anxiety-related behaviors, but effects on social behaviors are not well defined. The present study examined MS effects on female social behaviors in the social investigation (SIT) and social preference (SPT) tests, in addition to non-social behaviors in the open-field (OFT) and light-dark transition (LDT) tests in C57BL/6J mice. All females were tested as ovariectomized to eliminate confounding effects of endogenous estrogen during behavioral testing. Daily MS (3 hr) from postnatal day 1 to 14 did not affect anxiety levels in LDT, but were elevated in OFT with modified behavioral responses to the novel environment. Furthermore, MS altered social investigative behaviors and preference patterns toward unfamiliar stimulus mice in SIT and short- and long-term SPT paradigms. In SIT, MS reduced social investigation duration and increased number of stretched approaches towards both female and male unfamiliar stimulus mice, suggesting increased social anxiety levels in MS females. Similarly, MS heightened levels of social anxiety during short-term SPT but no MS effect on social preference was found. On the other hand, MS females displayed a distinctive preference for female stimuli, unlike control females, when tested for long-term SPT over a prolonged period of 5 days. Evaluation of FosB expression in the paraventricular nucleus, medial and central amygdala following stimulus exposure demonstrated greater number of FosB immunopositive cells in all three brain regions in MS females compared to control females. These results suggest that MS females might differ in neuroendocrine responses toward unfamiliar female and male opponents, which may be associated with modifications in social behaviors found in the present study. Taken together, this study provides new evidence that early life stress modifies female social behaviors by highlighting alterations in behavioral responses to situations involving social as well as non-social novelty.

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Long-Lasting Sex-Specific Effects Based On Emotion- and Cognition-Related Behavioral Assessment of Adult Rats After Post-Traumatic Stress Disorder From Different Lengths of Maternal Separation.

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