Refine
Has Fulltext
- yes (57)
Is part of the Bibliography
- yes (57)
Year of publication
Document Type
- Journal article (57)
Language
- English (57) (remove)
Keywords
- ADHD (7)
- mice (7)
- anxiety (5)
- depression (5)
- serotonin (5)
- hippocampus (4)
- animal behavior (3)
- chronic stress (3)
- emotion (3)
- knockout mice (3)
Institute
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (35)
- Lehrstuhl für Molekulare Psychiatrie (23)
- Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie (6)
- Institut für Humangenetik (5)
- Theodor-Boveri-Institut für Biowissenschaften (5)
- Institut für Psychologie (3)
- Physiologisches Institut (3)
- Institut für Anatomie und Zellbiologie (2)
- Medizinische Klinik und Poliklinik I (2)
- Neurologische Klinik und Poliklinik (2)
- Rudolf-Virchow-Zentrum (2)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (1)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (1)
- Institut für Experimentelle Biomedizin (1)
- Institut für Klinische Neurobiologie (1)
- Institut für Molekulare Infektionsbiologie (1)
- Institut für Pädagogik (1)
- Julius-von-Sachs-Institut für Biowissenschaften (1)
- Kinderklinik und Poliklinik (1)
- Medizinische Klinik und Poliklinik II (1)
- Neurochirurgische Klinik und Poliklinik (1)
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 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.