Format

Send to

Choose Destination
Eur Neuropsychopharmacol. 2018 Nov;28(11):1270-1283. doi: 10.1016/j.euroneuro.2018.07.103. Epub 2018 Aug 23.

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

Author information

1
Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, Department of Psychiatry, University of Würzburg, Würzburg, Germany.
2
Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, Department of Psychiatry, University of Würzburg, Würzburg, Germany; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands. Electronic address: m.weidner@maastrichtuniversity.nl.
3
Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, Department of Psychiatry, University of Würzburg, Würzburg, Germany; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands; Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
4
Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Center of Mental Health, Department of Psychiatry, University of Würzburg, Würzburg, Germany; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands.

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 increased 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.

KEYWORDS:

Anxiety; Behaviour; Maternal separation; Mouse; Serotonin; c-Fos

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center