Relationship between post-traumatic stress disorder-like behavior and reduction of hippocampal 5-bromo-2′-deoxyuridine-positive cells after inescapable shock in rats


*Masashi Nibuya, PhD, Department of Psychiatry, National Defense Medical College, Namiki 3-2, Tokorozawa, Saitama 359-8513, Japan. Email:


Aim:  Inescapable shocks (IS) have been reported to reduce the number of 5-bromo-2′-deoxyuridine (BrdU)-positive cells in hippocampus. Antidepressants prevent this reduction, and the role of neurogenesis in depression is now suggested. It has been reported, however, that the number of BrdU-positive cells was not different between the rats that developed learned helplessness and those that did not. This suggests that reduction of neurogenesis does not constitute a primary etiology of depression. It has been previously shown that IS can cause various post-traumatic stress disorder (PTSD)-like behavioral changes in rats. The aim of the present was therefore to examined whether the reduction of BrdU-positive cells relates to any PTSD-like behavioral changes in this paradigm.

Methods:  Rats were given either inescapable foot-shocks (IS) or not shocked (non-S) treatment in a shuttle box on day 1 and received BrdU injections once daily during the first week after IS/non-S treatment. On day 14, rats treated with IS and non-S were given an avoidance/escape test in the shuttle box and dorsal hippocampal SGZ were analyzed by BrdU immunohistochemistry.

Results:  In accordance with previously reported results, IS loading resulted in fewer BrdU-positive cells in the hippocampal subgranular zone (SGZ). Furthermore, in the IS-treated group, the number of BrdU-positive cells in the hippocampal SGZ was negatively correlated at a significant level with several hyperactive behavioral parameters but not with hypoactive behavioral parameters. Earlier findings had indicated that chronic selective serotonin re-uptake inhibitor administration, which is known to increase hippocampal neurogenesis, restored the increase in hypervigilant/hyperarousal behavior but did not attenuate the increase in numbing/avoidance behavior.

Conclusion:  The regulatory mechanism responsible for the decreased proliferation and survival of cells in the hippocampus may be related to the pathogenic processes of hypervigilance/hyperarousal behaviors.