The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

Journal Article

Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the development of anxiety- or impulsivity-like behaviour has not been established. Here, we examined the effects of early life maternal separation (MS) stress on anxiety-like behaviour and behavioural disinhibition, a type of impulsivity-like behaviour, in wild-type (WT) and tryptophan hydroxylase 2 (Tph2) knock-in (Tph2KI) mice, which exhibit ~60-80% reductions in the levels of brain 5-HT due to a R439H mutation in Tph2. We also investigated the effects of 5-HT deficiency and early life stress on adult hippocampal neurogenesis, plasma corticosterone levels and several signal transduction pathways in the amygdala. We demonstrate that MS slightly increases anxiety-like behaviour in WT mice and induces behavioural disinhibition in Tph2KI animals. We also demonstrate that MS leads to a slight decrease in cell proliferation within the hippocampus and potentiates corticosterone responses to acute stress, but these effects are not affected by brain 5-HT deficiency. However, we show that 5-HT deficiency leads to significant alterations in SGK-1 and GSK3β signalling and NMDA receptor expression in the amygdala in response to MS. Together, these findings support a potential role for 5-HT-dependent signalling in the amygdala in regulating the long-term effects of early life stress on anxiety-like behaviour and behavioural disinhibition.

Full Text

Duke Authors

Cited Authors

  • Sachs, BD; Rodriguiz, RM; Siesser, WB; Kenan, A; Royer, EL; Jacobsen, JPR; Wetsel, WC; Caron, MG

Published Date

  • October 2013

Published In

Volume / Issue

  • 16 / 9

Start / End Page

  • 2081 - 2094

PubMed ID

  • 23672796

Electronic International Standard Serial Number (EISSN)

  • 1469-5111

Digital Object Identifier (DOI)

  • 10.1017/S1461145713000321

Language

  • eng

Conference Location

  • England