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


CONCLUSIONS
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.
Kikuchi
Akihito
A
Division of Behavioral Sciences, National Defense Medical College Research Institute, Tokyo, Japan.
Shimizu
Kunio
K
Nibuya
Masashi
M
Hiramoto
Takeshi
T
Kanda
Yasunari
Y
Tanaka
Teppei
T
Watanabe
Yasuhiro
Y
Takahashi
Yoshitomo
Y
Nomura
Soichiro
S
D000818:Animals; D000963:Antimetabolites; D001362:Avoidance Learning / Q000502:physiology; D001973:Bromodeoxyuridine; D004597:Electroshock; D004924:Escape Reaction / Q000502:physiology; D006380:Helplessness, Learned; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013313:Stress Disorders, Post-Traumatic / Q000473:pathology* / Q000523:psychology*
D000963:Antimetabolites; D001973:Bromodeoxyuridine