ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2009
Paradoxical anxiogenic response of juvenile mice to fluoxetine.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.
- The effect of SSRIs on unconditioned anxiety: a systematic review and meta-analysis of animal studies.Psychopharmacology · 2024Pooled it
- Effects of chronic fluoxetine treatment on anxiety- and depressive-like behaviors in adolescent rodents - systematic review and meta-analysis.Pharmacological reports : PR · 2022Pooled it
- Fluoxetine Disrupts Ovarian Serotonin Signaling and Oocyte Competence in Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- ERK2 Signaling in the Nucleus Accumbens Facilitates Stress Susceptibility and Cocaine Reinstatement.Biological psychiatry global open science · 2025Article
- The effects of Arabian jasmine on zebrafish behavior depends on strain, sex, and personality.PloS one · 2025Article
- Impact of fluoxetine preexposure on MDMA-induced taste avoidance in male and female rats.Experimental and clinical psychopharmacology · 2023Article
- Effect of selective serotonin reuptake inhibitor discontinuation on anxiety-like behaviours in mice.Journal of psychopharmacology (Oxford, England) · 2022Article
- Sex differences in specific aspects of two animal tests of anxiety-like behavior.Psychopharmacology · 2021Article
- Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain.International journal of molecular sciences · 2021Article
- 5-HTACS chemical neuroscience · 2021Article
- Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Photoperiodic effects on monoamine signaling and gene expression throughout development in the serotonin and dopamine systems.Scientific reports · 2020Article
- Mouse model of the human serotonin transporter-linked polymorphic region.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- 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
- Loss of Adult 5-HT1A Autoreceptors Results in a Paradoxical Anxiogenic Response to Antidepressant Treatment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Article
- Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice.The American journal of psychiatry · 2017Article
- Antidepressant responsiveness in adulthood is permanently impaired after neonatal destruction of the neurogenic pool.Translational psychiatry · 2017Article
- Nociceptin receptor antagonist SB 612111 decreases high fat diet binge eating.Behavioural brain research · 2016Article
- GluN2B-Containg NMDA Receptors on Adult-Born Granule Cells Contribute to the Antidepressant Action of Fluoxetine.Frontiers in neuroscience · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Depression, anxiety, and conduct disorders are common in children and adolescents, and selective serotonin reuptake inhibitors (SSRIs) are often used to treat these conditions. Fluoxetine (Prozac) is the first approved SSRI for the treatment of depression in this population. Although it is believed that overall, fluoxetine is effective in child and adolescent psychiatry, there have been reports of specific adverse drug effects, most prominently, suicidality and psychiatric symptoms such as agitation, worsening of depression, and anxiety. Chronic fluoxetine substantially increases brain extracellular 5-HT concentrations, and the juvenile developing brain may respond to supraphysiological 5-HT levels with specific adverse effects not seen or less prominent in adult brain. Using novelty-induced hypophagia, as well as open-field and elevated plus maze tests, we show that both Swiss Webster and C57Bl/6 mice, receiving fluoxetine in a clinically relevant dose and during their juvenile age corresponding to child-adolescent periods in humans, exhibit a paradoxical anxiogenic response. The adverse effects of juvenile fluoxetine disappeared upon drug discontinuation and no long-term behavioral consequences were apparent. No adverse effect to chronic fluoxetine was seen in adult mice and a dose-dependent anxiolytic effect developed. These data show that the age of the mice, independently of the strains and tests used in this study, is the determining factor of whether the response to chronic fluoxetine is anxiolytic or anxiogenic. Taken together, the response of the juvenile and adult brain to fluoxetine could be fundamentally different and the juvenile fluoxetine administration mouse model described here may help to identify the mechanism underlying this difference.
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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.