title: Prenatal stress, regardless of concurrent escitalopram treatment, alters behavior and amygdala gene expression of adolescent female rats.
abstract: Depression during pregnancy has been linked to in utero stress and is associated with long-lasting symptoms in offspring, including anxiety, helplessness, attentional deficits, and social withdrawal. Depression is diagnosed in 10-20% of expectant mothers, but the impact of antidepressant treatment on offspring development is not well documented, particularly for females. Here, we used a prenatal stress model of maternal depression to test the hypothesis that in utero antidepressant treatment could mitigate the effects of prenatal stress. We also investigated the effects of prenatal stress and antidepressant treatment on gene expression related to GABAergic and serotonergic neurotransmission in the amygdala, which may underlie behavioral effects of prenatal stress. Nulliparous female rats were implanted with osmotic minipumps delivering clinically-relevant concentrations of escitalopram and mated. Pregnant dams were exposed to 12 days of mixed-modality stressors, and offspring were behaviorally assessed in adolescence (postnatal day 28) and adulthood (beyond day 90) to determine the extent of behavioral change. We found that in utero stress exposure, regardless of escitalopram treatment, increased anxiety-like behavior in adolescent females and profoundly influenced amygdala expression of the chloride transporters KCC2 and NKCC1, which regulate GABAergic function. In contrast, prenatal escitalopram exposure alone elevated amygdala expression of 5-HT1A receptors. In adulthood, anxiety-like behavior returned to baseline and gene expression effects in the amygdala abated, whereas deficits emerged in novel object recognition for rats exposed to stress during gestation. These findings suggest prenatal stress causes age-dependent deficits in anxiety-like behavior and amygdala function in female offspring, regardless of antidepressant exposure.
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA; Division of Behavioral Neurosci. and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Ehrlich
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA; Dept. of Physiology, Emory University, Atlanta, GA, USA. Electronic address: gretchen.neigh@emory.edu.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA.
authors.forename: Chase H
authors.initials: CH
authors.lastname: Bourke
authors.affiliation: Dept. of Physiology, Emory University, Atlanta, GA, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Nemeth
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA; Division of Behavioral Neurosci. and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: Rimi
authors.initials: R
authors.lastname: Hazra
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA; Division of Behavioral Neurosci. and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ryan
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA.
authors.forename: Sydney
authors.initials: S
authors.lastname: Rowson
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA.
authors.forename: Nesha
authors.initials: N
authors.lastname: Jairam
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Sholar
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA; Division of Behavioral Neurosci. and Psychiatric Disorders, Yerkes National Primate Research Center, Atlanta, GA, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Rainnie
authors.affiliation: Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Zachary N
authors.initials: ZN
authors.lastname: Stowe
authors.affiliation: Dept. of Psychiatry and Behavioral Sci., Atlanta, GA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owens
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology*; D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology*; D015283:Citalopram / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology*; D027981:Symporters / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000096922:K Cl- Cotransporters
chemical_list: D015283:Citalopram; D003345:Corticosterone; D004958:Estradiol; D044282:Receptor, Serotonin, 5-HT1A; D017367:Selective Serotonin Reuptake Inhibitors; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C578879:Slc12a2 protein, rat
keywords: Antidepressant; Anxiety; Female; GABA; Prenatal stress; Serotonin