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Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.

Publication ,  Journal Article
Sachs, BD; Rodriguiz, RM; Tran, HL; Iyer, A; Wetsel, WC; Caron, MG
Published in: Psychoneuroendocrinology
March 2015

Brain 5-HT deficiency has long been implicated in psychiatric disease, but the effects of 5-HT deficiency on stress susceptibility remain largely unknown. Early life stress (ELS) has been suggested to contribute to adult psychopathology, but efforts to study the long-term consequences of ELS have been limited by a lack of appropriate preclinical models. Here, we evaluated the effects of 5-HT deficiency on several long-term cellular, molecular, and behavioral responses of mice to a new model of ELS that combines early-life maternal separation (MS) of pups and postpartum learned helplessness (LH) training in dams. Our data demonstrate that this paradigm (LH/MS) induces depressive-like behavior and impairs pup retrieval in dams. In addition, we show that brain 5-HT deficiency exacerbates anxiety-like behavior induced by LH/MS and blunts the effects of LH/MS on acoustic startle responses in adult offspring. Although the mechanisms underlying these effects remain unclear, following LH/MS, 5-HT-deficient animals had significantly less mRNA expression of the mineralocorticoid receptor in the amygdala than wild-type animals. In addition, 5-HT-deficient mice exhibited reduced mRNA levels of the 5-HT2a receptor and p11 in the hippocampus regardless of stress. LH/MS decreased the number of doublecortin+ immature neurons in the hippocampus in both wild-type (WT) and 5-HT-deficient animals. Our data emphasize the importance of complex interactions between genetic factors and early life experience in mediating long-term changes in emotional behavior. These findings may have important implications for our understanding of the combinatorial roles of 5-HT deficiency, ELS, and postpartum depression in the development of neuropsychiatric disorders.

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Published In

Psychoneuroendocrinology

DOI

EISSN

1873-3360

Publication Date

March 2015

Volume

53

Start / End Page

69 / 81

Location

England

Related Subject Headings

  • Tryptophan Hydroxylase
  • Stress, Psychological
  • Serotonin
  • Reflex, Startle
  • Reflex, Abnormal
  • Receptors, Mineralocorticoid
  • Receptor, Serotonin, 5-HT2A
  • RNA, Messenger
  • Psychiatry
  • Neurogenesis
 

Citation

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Sachs, B. D., Rodriguiz, R. M., Tran, H. L., Iyer, A., Wetsel, W. C., & Caron, M. G. (2015). Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience. Psychoneuroendocrinology, 53, 69–81. https://doi.org/10.1016/j.psyneuen.2014.12.019
Sachs, Benjamin D., Ramona M. Rodriguiz, Ha L. Tran, Akshita Iyer, William C. Wetsel, and Marc G. Caron. “Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.Psychoneuroendocrinology 53 (March 2015): 69–81. https://doi.org/10.1016/j.psyneuen.2014.12.019.
Sachs BD, Rodriguiz RM, Tran HL, Iyer A, Wetsel WC, Caron MG. Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience. Psychoneuroendocrinology. 2015 Mar;53:69–81.
Sachs, Benjamin D., et al. “Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.Psychoneuroendocrinology, vol. 53, Mar. 2015, pp. 69–81. Pubmed, doi:10.1016/j.psyneuen.2014.12.019.
Sachs BD, Rodriguiz RM, Tran HL, Iyer A, Wetsel WC, Caron MG. Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience. Psychoneuroendocrinology. 2015 Mar;53:69–81.
Journal cover image

Published In

Psychoneuroendocrinology

DOI

EISSN

1873-3360

Publication Date

March 2015

Volume

53

Start / End Page

69 / 81

Location

England

Related Subject Headings

  • Tryptophan Hydroxylase
  • Stress, Psychological
  • Serotonin
  • Reflex, Startle
  • Reflex, Abnormal
  • Receptors, Mineralocorticoid
  • Receptor, Serotonin, 5-HT2A
  • RNA, Messenger
  • Psychiatry
  • Neurogenesis