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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Sachs, BD; Rodriguiz, RM; Tran, HL; Iyer, A; Wetsel, WC; Caron, MG

Published Date

  • March 2015

Published In

Volume / Issue

  • 53 /

Start / End Page

  • 69 - 81

PubMed ID

  • 25602134

Pubmed Central ID

  • PMC4344834

Electronic International Standard Serial Number (EISSN)

  • 1873-3360

Digital Object Identifier (DOI)

  • 10.1016/j.psyneuen.2014.12.019


  • eng

Conference Location

  • England