Improved Stress Control in Serotonin Transporter Knockout Rats: Involvement of the Prefrontal Cortex and Dorsal Raphe Nucleus

Pieter Schipper, Dora Lopresto, Roy J. Reintjes, Joep Joosten, Marloes J.A.G. Henckens, Tamas Kozicz, Judith R. Homberg

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Variations in serotonin transporter (5-HTT) expression have been associated with altered sensitivity to stress. Since controllability is known to alter the impact of a stressor through differential activation of the medial prefrontal cortex (mPFC) and dorsal raphe nucleus (DRN), and that these regions are functionally affected by genetic 5-HTT down-regulation, we hypothesized that 5-HTT expression modulates the effect of controllability on stressor impact and coping. Here, we investigated the effects of a signaled stress controllability task or a yoked uncontrollable stressor on behavioral responding and mPFC and DRN activation. 5-HTT-/- rats proved better capable of acquiring the active avoidance task than 5-HTT+/+ animals. Controllability determined DRN activation in 5-HTT+/+, but not 5-HTT-/-, rats, whereas controllability-related activation of the mPFC was independent of genotype. These findings suggest that serotonergic activation in the DRN is involved in stress coping in a 5-HTT expression dependent manner, whereas mPFC activation seems to be implicated in control over stress independently of 5-HTT expression. We speculate that alterations in serotonergic feedback in the DRN might be a potential mechanism driving this differential stress coping.

Original languageEnglish (US)
Pages (from-to)1143-1150
Number of pages8
JournalACS Chemical Neuroscience
Volume6
Issue number7
DOIs
StatePublished - Jul 15 2015
Externally publishedYes

Keywords

  • avoidance
  • controllability
  • dorsal raphe nucleus
  • Serotonin
  • serotonin transporter
  • stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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