A postpartum model in rat: behavioral and gene expression changes induced by ovarian steroid deprivation.
BACKGROUND
Postpartum depression (PPD) affects approximately 10% to 20% of women during the first 4 weeks of the postpartum period and is characterized by labile mood with prominent anxiety and irritability, insomnia, and depressive mood. During the postpartum period, elevated ovarian hormones abruptly decrease to the early follicular phase levels that are postulated to play a major role in triggering PPD. However, the underlying neurobiological mechanisms that contribute to PPD have not been determined.


METHODS
In the present study, we examined the effect of ovarian steroids, administered at levels that occur during human pregnancy followed by rapid withdrawal to simulate postpartum conditions, on behavior and gene expression in the rat.


RESULTS
The results of behavioral testing reveal that the hormone-simulated postpartum treatment results in the development of a phenotype relevant to PPD, including vulnerability for helplessness, increased anxiety, and aggression. Real-time quantitative polymerase chain reaction (PCR) demonstrated transient regulation of several genes, including Ca(2+)/calmodulin-dependent protein kinase II (CAMKII), serotonin transporter (SERT), myocyte enhancer factor 2A (MEF2A), brain-derived neurotrophic factor (BDNF), gamma-aminobutyric acid type A receptor alpha 4 (GABAARA4), mothers against decapentaplegic homolog 4 (SMAD4), and aquaporin 4 (AQP4) that could underlie these behavioral effects.


CONCLUSIONS
These studies provide an improved understanding of the effects of withdrawal from high doses of ovarian hormones on behavior and gene expression changes in the brain that could contribute to the pathophysiology of PPD.
Suda
Shiro
S
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
Segi-Nishida
Eri
E
Newton
Samuel S
SS
Duman
Ronald S
RS
D000704:Analysis of Variance; D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D019052:Depression, Postpartum / Q000209:etiology / Q000235:genetics / Q000523:psychology; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006380:Helplessness, Learned; D064326:MEF2 Transcription Factors; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D049590:Postpartum Period / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D013550:Swimming
D051401:Aquaporin 4; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D013256:Steroids; D004958:Estradiol; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2