The effects of repeated social defeat on long-term depressive-like behavior and short-term histone modifications in the hippocampus in male Sprague-Dawley rats.
BACKGROUND
Social stress has been linked to several neuropsychiatric diseases, including depression, which is a debilitating disease that has genetic, environmental, and epigenetic underpinnings.


OBJECTIVE
This study examined the effects of repeated social defeat on both depressive-like behaviors and histone acetylation in the hippocampus, amygdala, and dorsal prefrontal cortex of male Sprague-Dawley rats.


METHODS
Subjects were exposed to four consecutive social defeats. Depressive-like behaviors were assayed in the sucrose preference, forced swim, contextual fear, and social approach and avoidance tests. Histone H3 and H4 acetylation in the hippocampus, amygdala, and prefrontal cortex were examined by Western blots under basal conditions and at several time points. We also investigated the potential involvement of N-methyl-D: -aspartic acid (NMDA) receptors and glucocorticoid receptors (GR) by injecting respective antagonists prior to each social defeat and examining their effect on histone acetylation in the hippocampus.


RESULTS
Social defeat resulted in behavioral changes in the forced swim, social avoidance, and contextual fear tests nearly 6 weeks after defeat, with no change in sucrose preference. Additionally, histone H3 acetylation was increased in the hippocampus 30 min following the last defeat and was not blocked by antagonism of either NMDA or GR receptors. There were no changes in histone H4 acetylation.


CONCLUSIONS
These results indicate that social defeat induces several long-lasting depressive-like behaviors in rats and induces a significant, short-lived increase in H3 acetylation in the hippocampus, although the underlying mechanism behind this change warrants further investigation.
Hollis
Fiona
F
Department of Biomedical Sciences, Florida State University College of Medicine, 1115 W. Call St., Tallahassee, FL 32306, USA.
Wang
Hui
H
Dietz
David
D
Gunjan
Akash
A
Kabbaj
Mohamed
M
D000107:Acetylation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005518:Food Preferences / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012930:Social Dominance; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D006657:Histones; D016291:Dizocilpine Maleate
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