Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-154586
- 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-HT synthesis 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 resultingRationale 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-HT synthesis 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-pituitary-adrenocortical (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 emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{−/−}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Conclusions Our 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.…
Autor(en): | Lise Gutknecht, Sandy Popp, Jonas Waider, Frank M. J. Sommerlandt, Corinna Göppner, Antonia Post, Andreas Reif, Daniel van den Hove, Tatyana Strekalova, Angelika Schmitt, Maria B. N. Colaςo, Claudia Sommer, Rupert Palme, Klaus-Peter Lesch |
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URN: | urn:nbn:de:bvb:20-opus-154586 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Neurologische Klinik und Poliklinik |
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Psychopharmacology |
Erscheinungsjahr: | 2015 |
Band / Jahrgang: | 232 |
Erste Seite: | 2429 |
Letzte Seite: | 2441 |
Originalveröffentlichung / Quelle: | Psychopharmacology (2015) 232:2429–2441. DOI: 10.1007/s00213-015-3879-0 |
DOI: | https://doi.org/10.1007/s00213-015-3879-0 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | Serotonin; Tryptophan hydroxylase-2 (Tph2); aggression; anxiety; chronic stress; depression; fear; gene-by-environment interaction |
Datum der Freischaltung: | 07.11.2017 |
EU-Projektnummer / Contract (GA) number: | 602805 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung |