ArticlePsychopharmacology2015
Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice.
Article in Psychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 104 citations in OpenAlex.
- Serotonin deficiency caused by inactivation of Tph2 in mice leads to widespread sex-dependent changes in cerebral oxidative metabolic activity.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Decoding the serotonin-alcohol crosstalk: the role of central serotonergic dysregulation in alcohol use disorder.Pharmacological reports : PR · 2026Review
- Associations of genetic polymorphisms with boldness, stress response, and route efficiency in homing pigeons (Columba livia).Physiology & behavior · 2026Article
- Oral tryptophan supplementation to suckling piglets affecting hypothalamic serotonin metabolism, behavior, and growth in the nursery period under social mixing stress.Journal of animal science · 2025Article
- Socio-affective communication in Tph2-deficient rat pups: communal nesting aggravates growth retardation despite ameliorating maternal affiliation deficits.Molecular autism · 2024Article
- Article
- Ethanol deprivation and central 5-HT deficiency differentially affect the mRNA editing of the 5-HTPharmacological reports : PR · 2023Article
- Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis.Journal of neural transmission (Vienna, Austria : 1996) · 2023Article
- Defensive and Emotional Behavior Modulation by Serotonin in the Periaqueductal Gray.Cellular and molecular neurobiology · 2023Review
- Elevated levels of serotonin 5-HTEuropean archives of psychiatry and clinical neuroscience · 2023Article
- 5-HT attenuates chronic stress-induced cognitive impairment in mice through intestinal flora disruption.Journal of neuroinflammation · 2023Article
- Maternal methyl donor supplementation regulates the effects of cafeteria diet on behavioral changes and nutritional status in male offspring.Food & nutrition research · 2023Article
- Enhanced Aggression, Reduced Self-Grooming Behavior and Altered 5-HT Regulation in the Frontal Cortex in Mice Lacking Trace Amine-Associated Receptor 1 (TAAR1).International journal of molecular sciences · 2022Article
- Tryptophan Hydroxylase 2 Knockout Male Rats Exhibit a Strengthened Oxytocin System, Are Aggressive, and Are Less Anxious.ACS chemical neuroscience · 2022Article
- Effect of Acute Cold Stress on Neuroethology in Mice and Establishment of Its Model.Animals : an open access journal from MDPI · 2022Article
- Review
- Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors.Cell communication and signaling : CCS · 2022Article
- Article
- Article
- Resilience to the effects of social stress on vulnerability to developing drug addiction.World journal of psychiatry · 2022Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleWhile 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.
objectiveHere, 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.
resultsLocomotor 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.
conclusionsOur 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.
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