Multiple stress induces amygdalohippocampal volume reduction in adult male rats as detected by longitudinal structural magnetic resonance imaging

Background Prior traumatic events can cause long-lasting and uncontrollable fear and anxiety. Posttraumatic stress disorder (PTSD) is an intractable mental disorder, and neurobiological mechanisms using animal models are expected to help in PTSD treatment. In this study, we combined the multiple stress (MS) and longitudinal in vivo magnetic resonance imaging (MRI) to reveal the effects of long-lasting anxiety-like behaviors on adult male rat brains. Methods Twelve male Wistar rats (8-weeks old) were exposed to MS of 1 mA foot shocks and forced swimming, while 12 control rats were placed in a plastic cage. Contextual fear conditioning with 0.1 mA foot shocks in a context different from the MS was conducted 15 days after the MS for both the groups. Three retention tests were administered after 24 h and 9 and 16 days. Two MRI scans were conducted on the day before MS induction and the day after the third retention test with 32 days interval. Results The MS group showed greater freezing responses than the control group in all retention tests. Whole-brain voxel-based morphometry analyses revealed reduced gray matter volume in the anterior amygdalohippocampal area in MS group rats compared to that in control rats. These volume changes were negatively associated with freezing time in the third retention test in the MS group. Conclusion These results suggest that individual variability in the amygdalohippocampal area may be related to long-lasting fear responses after severe stress.