ArticlePloS one2011
Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 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
- The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design.BMC psychiatry · 2014Trial
- Exercise and fluoxetine in Alzheimer's disease: Molecular mechanisms of synergistic and antagonistic effects (Review).International journal of molecular medicine · 2026Review
- Juvenile fluoxetine treatment affects the maturation of the medial prefrontal cortex and behavior of adolescent female rats.Pharmacological reports : PR · 2025Article
- Alterations of Adult Prefrontal Circuits Induced by Early Postnatal Fluoxetine Treatment Mediated by 5-HT7 Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Acute and long-lasting effects of adolescent fluoxetine exposure on feeding behavior in Sprague-Dawley rats.Developmental psychobiology · 2022Article
- Effect of early-life stress or fluoxetine exposure on later-life conditioned taste aversion learning in Sprague-Dawley rats.Neuroscience letters · 2022Article
- Adolescent fluoxetine exposure increases ERK-related signaling within the prefrontal cortex of adult male Sprague-Dawley rats.Oxford open neuroscience · 2022Article
- Sex differences in specific aspects of two animal tests of anxiety-like behavior.Psychopharmacology · 2021Article
- Adolescent fluoxetine treatment mediates a persistent anxiety-like outcome in female C57BL/6 mice that is ameliorated by fluoxetine re-exposure in adulthood.Scientific reports · 2021Article
- Adolescent Fluoxetine Exposure Induces Persistent Gene Expression Changes in the Hippocampus of Adult Male C57BL/6 Mice.Molecular neurobiology · 2021Article
- Autophagy Induction and Accumulation of Phosphorylated Tau in the Hippocampus and Prefrontal Cortex of Adult C57BL/6 Mice Subjected to Adolescent Fluoxetine Treatment.Journal of Alzheimer's disease : JAD · 2021Article
- Environmental Enrichment and Physical Exercise Attenuate the Depressive-Like Effects Induced by Social Isolation Stress in Rats.Frontiers in pharmacology · 2020Article
- Adolescent fluoxetine history impairs spatial memory in adult male, but not female, C57BL/6 mice.Journal of affective disorders · 2019Article
- Neurodevelopmental and behavioral consequences of perinatal exposure to the HIV drug efavirenz in a rodent model.Translational psychiatry · 2019Article
- Targeting Serotonin Transporters in the Treatment of Juvenile and Adolescent Depression.Frontiers in neuroscience · 2019Article
- Article
- Fluoxetine exposure in adolescent and adult female mice decreases cocaine and sucrose preference later in life.Journal of psychopharmacology (Oxford, England) · 2018Article
- Heterogeneous stock rats: a model to study the genetics of despair-like behavior in adolescence.Genes, brain, and behavior · 2018Article
- Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531).Frontiers in behavioral neuroscience · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A) receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine-induced neuroplasticity in the amygdala.
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Registered trials
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