Differential anxiety-related behaviours and brain activation in Tph2-deficient female mice exposed to adverse early environment

Charlotte S. Auth, Magdalena T. Weidner*, Sandy Popp, Tatyana Strekalova, Angelika G. Schmitt-Boehrer, Daniel L. A. van den Hove, Klaus-Peter Lesch, Jonas Waider

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Anxiety disorders represent one of the most prevalent mental disorders in today's society and early adversity has been identified as major contributor to anxiety-related pathologies. Serotonin (5-hydroxytryptamine, 5-HT) is implicated in mediating the effects of early-life events on anxiety-like behaviours. In order to further elucidate the interaction of genetic predisposition and adversity in early, developmental stages on anxiety-related behaviours, the current study employed tryptophan hydroxylase 2 (Tph2)-deficient female mice, as a model for lifelong brain 5-HT synthesis deficiency. Offspring of this line were exposed to maternal separation (MS) and tested, in the open-field (OF) or the dark-light box (DLB). Subsequently, neural activity was assessed, using c-Fos immunohistochemistry. In the DLB, MS rescued the observed decrease in activity in the light compartment of homozygous Tph2-deficient mice and furthermore in-creased the incidence of escape-related jumps in animals of the same genotype. In the OF, MS increased escape-related behaviours in homo-and heterozygous Tph2-deficient offspring. On the neural level, both behavioural tests evoked a distinct activation pattern, as shown by c-Fos immunohistochemistry. Exposure to the DLB resulted in Tph2-dependent activation of paraventricular nucleus and basolateral amygdala, while OF exposure led to a specific activation in lateral amygdala of maternally separated animals and a Tph2 genotype-and MS-dependent activation of the ventrolateral and dorsolateral periaqueductal grey. Taken together, our findings suggest that MS promotes active responses to aversive stimuli, dependent on the availability of brain 5-HT. These effects might be mediated by the distinct activation of anxiety-relevant brain regions, due to the behavioural testing. (c) 2018 Elsevier B.V. and ECNP. All rights reserved.

Original languageEnglish
Pages (from-to)1270-1283
Number of pages14
JournalEuropean Neuropsychopharmacology
Volume28
Issue number11
DOIs
Publication statusPublished - Nov 2018

Keywords

  • Serotonin
  • Maternal separation
  • c-Fos
  • Anxiety
  • Mouse
  • Behaviour
  • CORTICOTROPIN-RELEASING-FACTOR
  • C-FOS EXPRESSION
  • NEONATAL MATERNAL SEPARATION
  • DORSAL PERIAQUEDUCTAL GRAY
  • OPEN-FIELD TEST
  • MESSENGER-RNA
  • HYPOTHALAMIC VASOPRESSIN
  • DEAKIN/GRAEFF HYPOTHESIS
  • INDIVIDUAL-DIFFERENCES
  • SEROTONERGIC NEURONS

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