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 language | English |
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Pages (from-to) | 1270-1283 |
Number of pages | 14 |
Journal | European Neuropsychopharmacology |
Volume | 28 |
Issue number | 11 |
DOIs | |
Publication status | Published - 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