ArticleACS chemical neuroscience2014
Mice genetically depleted of brain serotonin do not display a depression-like behavioral phenotype.
Article in ACS chemical neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Use of Spirituality in the Treatment of Depression: Systematic Literature Review.The Psychiatric quarterly · 2022Pooled it
- 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
- Kynurenine pathway dysregulation in major depressive disorder: the convergence of excitotoxicity, neuroinflammation, and oxidative stress.Journal of neuroinflammation · 2026Review
- Neuropsychiatric Abnormalities in Metabolic Disturbances: Interplay of Adipokines and Neurotransmission.Molecular neurobiology · 2025Review
- Socio-affective communication in Tph2-deficient rat pups: communal nesting aggravates growth retardation despite ameliorating maternal affiliation deficits.Molecular autism · 2024Article
- Role of the circadian nuclear receptor REV-ERBα in dorsal raphe serotonin synthesis in mood regulation.Communications biology · 2024Article
- Ethanol deprivation and central 5-HT deficiency differentially affect the mRNA editing of the 5-HTPharmacological reports : PR · 2023Article
- Article
- The First Dipeptide Mimetic of Neurotrofin-3: Design and Pharmacological Properties.Doklady. Biochemistry and biophysics · 2022Article
- Article
- Antidepressant-like Effects of BDNF and NGF Individual Loop Dipeptide Mimetics Depend on the Signal Transmission Patterns Associated with Trk.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Implantable aptamer-field-effect transistor neuroprobes for in vivo neurotransmitter monitoring.Science advances · 2021Article
- Serotonin deficiency induced after brain maturation rescues consequences of early life adversity.Scientific reports · 2021Article
- Responses to chronic corticosterone on brain glucocorticoid receptors, adrenal gland, and gut microbiota in mice lacking neuronal serotonin.Brain research · 2021Article
- Serotonin Transporter and Plasma Membrane Monoamine Transporter Are Necessary for the Antidepressant-Like Effects of Ketamine in Mice.International journal of molecular sciences · 2020Article
- Effects of a high fat diet on gut microbiome dysbiosis in a mouse model of Gulf War Illness.Scientific reports · 2020Article
- Thorium exerts hazardous effects on some neurotransmitters and thyroid hormones in adult male rats.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Food Anticipatory Activity on Circadian Time Scales Is Not Dependent on Central Serotonin: Evidence From Tryptophan Hydroxylase-2 and Serotonin Transporter Knockout Mice.Frontiers in molecular neuroscience · 2020Article
- Dissociation between hypothermia and neurotoxicity caused by mephedrone and methcathinone in TPH2 knockout mice.Psychopharmacology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Reductions in function within the serotonin (5HT) neuronal system have long been proposed as etiological factors in depression. Selective serotonin reuptake inhibitors (SSRIs) are the most common treatment for depression, and their therapeutic effect is generally attributed to their ability to increase the synaptic levels of 5HT. Tryptophan hydroxylase 2 (TPH2) is the initial and rate-limiting enzyme in the biosynthetic pathway of 5HT in the CNS, and losses in its catalytic activity lead to reductions in 5HT production and release. The time differential between the onset of 5HT reuptake inhibition by SSRIs (minutes) and onset of their antidepressant efficacy (weeks to months), when considered with their overall poor therapeutic effectiveness, has cast some doubt on the role of 5HT in depression. Mice lacking the gene for TPH2 are genetically depleted of brain 5HT and were tested for a depression-like behavioral phenotype using a battery of valid tests for affective-like disorders in animals. The behavior of TPH2(-/-) mice on the sucrose preference test, tail suspension test, and forced swim test and their responses in the unpredictable chronic mild stress and learned helplessness paradigms was the same as wild-type controls. While TPH2(-/-) mice as a group were not responsive to SSRIs, a subset responded to treatment with SSRIs in the same manner as wild-type controls with significant reductions in immobility time on the tail suspension test, indicative of antidepressant drug effects. The behavioral phenotype of the TPH2(-/-) mouse questions the role of 5HT in depression. Furthermore, the TPH2(-/-) mouse may serve as a useful model in the search for new medications that have therapeutic targets for depression that are outside of the 5HT neuronal system.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.