Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice
Lise Gutknecht,Lise Gutknecht,Sandy Popp,Jonas Waider,Frank M. J. Sommerlandt,Corinna Göppner,Antonia Post,Andreas Reif,Daniel L.A. van den Hove,Tatyana Strekalova,Angelika Schmitt,Maria B. N. Colaςo,Claudia Sommer,Rupert Palme,Klaus-Peter Lesch,Klaus-Peter Lesch +15 more
TLDR
The results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.Abstract:
Rationale While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HTsynthesis and environmental stressors is linked to failure in emotion regulation. Objective Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Results Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2 �/� ) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitaryadrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2 �/� males displayed increased impulsivity and high aggressiveness. Tph2 �/� females displayed greater emotionalread more
Citations
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References
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TL;DR: It is shown that hyperactivity of the hypothalamic-pituitary-adrenal axis is one of the most consistent biological findings in major depression psychiatry, but the mechanisms underlying this abnormality are still unclear.
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Chronic Mild Stress (CMS) Revisited: Consistency and Behavioural-Neurobiological Concordance in the Effects of CMS
TL;DR: There is overwhelming evidence that under appropriate experimental conditions, CMS can cause antidepressant-reversible depressive-like effects in rodents; however, the ‘anomalous’ profile that is occasionally reported appears to be a genuine phenomenon, and these two sets of behavioural effects appear to be associated with opposite patterns of neurobiological changes.
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Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states
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Hans-Christian Pape,Denis Paré +1 more
TL;DR: Pavlovian fear conditioning as a model and the amygdala as a key component for the acquisition and extinction of fear responses are focused on.
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