ArticleTranslational psychiatry2013
The effects of congenital brain serotonin deficiency on responses to chronic fluoxetine.
Article in Translational psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Effects of chronic fluoxetine treatment on anxiety- and depressive-like behaviors in adolescent rodents - systematic review and meta-analysis.Pharmacological reports : PR · 2022Pooled it
- Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.Translational psychiatry · 2023Article
- Long-Term Soft-Food Rearing in Young Mice Alters Brain Function and Mood-Related Behavior.Nutrients · 2023Article
- Brain serotonin deficiency and fluoxetine lead to sex-specific effects on binge-like food consumption in mice.Psychopharmacology · 2022Article
- Antidepressant Like Effect of Ascorbic Acid in Mice: Possible Involvement of NO-sGC-cGMP Signaling.Neurochemical research · 2022Article
- Possible involvement of NO-sGC-cGMP signaling in the antidepressant like effect of pyridoxine in mice.Metabolic brain disease · 2022Article
- Fluoxetine increases brain MeCP2 immuno-positive cells in a female Mecp2 heterozygous mouse model of Rett syndrome through endogenous serotonin.Scientific reports · 2021Article
- Constitutive Serotonin Tone Modulates Molecular and Behavioral Response to Chronic Fluoxetine Treatment: A Study on Genetic Rat Model.Frontiers in psychiatry · 2021Article
- The Effects of Brain Serotonin Deficiency on Responses to High Fat Diet in Female Mice.Frontiers in neuroscience · 2021Article
- Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer's model of adult zebrafish brain.PLoS biology · 2020Article
- Novel aspects of enteric serotonergic signaling in health and brain-gut disease.American journal of physiology. Gastrointestinal and liver physiology · 2020Review
- Slow-release delivery enhances the pharmacological properties of oral 5-hydroxytryptophan: mouse proof-of-concept.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
- Effects of Serotonin and Slow-Release 5-Hydroxytryptophan on Gastrointestinal Motility in a Mouse Model of Depression.Gastroenterology · 2019Article
- 5-HTT independent effects of fluoxetine on neuroplasticity.Scientific reports · 2019Article
- Differential Hippocampal Expression of BDNF Isoforms and Their Receptors Under Diverse Configurations of the Serotonergic System in a Mice Model of Increased Neuronal Survival.Frontiers in cellular neuroscience · 2019Article
- Brain 5-HT Deficiency Prevents Antidepressant-Like Effects of High-Fat-Diet and Blocks High-Fat-Diet-Induced GSK3β Phosphorylation in the Hippocampus.Frontiers in molecular neuroscience · 2019Article
- Brain-region-specific Molecular Responses to Maternal Separation and Social Defeat Stress in Mice.Neuroscience · 2018Article
- Reducing central serotonin in adulthood promotes hippocampal neurogenesis.Scientific reports · 2016Article
- Symptoms of Poststroke Depression among Stroke Survivors: An Appraisal of Psychiatry Needs and Care during Physiotherapy Rehabilitation.Scientifica · 2016Article
- Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.Psychoneuroendocrinology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The importance of reversing brain serotonin (5-HT) deficiency and promoting hippocampal neurogenesis in the mechanisms of action for antidepressants remain highly controversial. Here we examined the behavioral, neurochemical and neurogenic effects of chronic fluoxetine (FLX) in a mouse model of congenital 5-HT deficiency, the tryptophan hydroxylase 2 (R439H) knock-in (Tph2KI) mouse. Our results demonstrate that congenital 5-HT deficiency prevents a subset of the signature molecular, cellular and behavioral effects of FLX, despite the fact that FLX restores the 5-HT levels of Tph2KI mice to essentially the levels observed in wild-type mice at baseline. These results suggest that inducing supra-physiological levels of 5-HT, not merely reversing 5-HT deficiency, is required for many of the antidepressant-like effects of FLX. We also demonstrate that co-administration of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), along with FLX rescues the novelty suppressed feeding (NSF) anxiolytic-like effect of FLX in Tph2KI mice, despite still failing to induce neurogenesis. Thus, our results indicate that brain 5-HT deficiency reduces the efficacy of FLX and that supplementation with 5-HTP can restore some antidepressant-like responses in the context of 5-HT deficiency. Our findings also suggest that feeding latency reductions in the NSF induced by chronic 5-HT elevation are not mediated by drug-induced increments in neurogenesis in 5-HT-deficient animals. Overall, these findings shed new light on the impact of 5-HT deficiency on responses to FLX and may have important implications for treatment selection in depression and anxiety disorders.
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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.