ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Juvenile administration of concomitant methylphenidate and fluoxetine alters behavioral reactivity to reward- and mood-related stimuli and disrupts ventral tegmental area gene expression in adulthood.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 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
- Dopamine and serotonin neurotransmissions exert complementary control over primate approach and avoidance.Translational psychiatry · 2025Article
- Serotonin-dopamine interactions in psychostimulant-induced gene regulation: SSRI antidepressants potentiate gene regulation by methylphenidate (Ritalin) in the striatum and enhance behavioral profile indicative of addiction liability in rodents.Neuroscience and biobehavioral reviews · 2025Review
- Juvenile fluoxetine treatment affects the maturation of the medial prefrontal cortex and behavior of adolescent female rats.Pharmacological reports : PR · 2025Article
- ERK2 Signaling in the Nucleus Accumbens Facilitates Stress Susceptibility and Cocaine Reinstatement.Biological psychiatry global open science · 2025Article
- Dopaminergic Remodeling During a Critical Developmental Window: Linking Drug Use to Adult Aggression.Neuroscience bulletin · 2024Article
- Fluoxetine potentiates methylphenidate-induced behavioral responses: Enhanced locomotion or stereotypies and facilitated acquisition of cocaine self-administration.Addiction neuroscience · 2023Article
- Chronic oral methylphenidate plus fluoxetine treatment in adolescent rats increases cocaine self-administration.Addiction neuroscience · 2023Article
- Alprazolam exposure during adolescence induces long-lasting dysregulation in reward sensitivity to morphine and second messenger signaling in the VTA-NAc pathway.Scientific reports · 2023Article
- Behavioral, Neurochemical and Developmental Effects of Chronic Oral Methylphenidate: A Review.Journal of personalized medicine · 2023Review
- From attention-deficit hyperactivity disorder to sporadic Alzheimer's disease-Wnt/mTOR pathways hypothesis.Frontiers in neuroscience · 2023Article
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- Effect of early-life stress or fluoxetine exposure on later-life conditioned taste aversion learning in Sprague-Dawley rats.Neuroscience letters · 2022Article
- Branched-chain amino acids linked to depression in young adults.Frontiers in neuroscience · 2022Article
- Fluoxetine Potentiates Oral Methylphenidate-Induced Gene Regulation in the Rat Striatum.Molecular neurobiology · 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
- Dietary intake of branched-chain amino acids in relation to depression, anxiety and psychological distress.Nutrition journal · 2021Article
- Exposure to Vicarious Social Defeat Stress and Western-Style Diets During Adolescence Leads to Physiological Dysregulation, Decreases in Reward Sensitivity, and Reduced Antidepressant Efficacy in Adulthood.Frontiers in neuroscience · 2021Article
- Rostrocaudal subregions of the ventral tegmental area are differentially impacted by chronic stress.Psychopharmacology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
There is a rise in the concurrent use of methylphenidate (MPH) and fluoxetine (FLX) in pediatric populations. However, the long-term neurobiological consequences of combined MPH and FLX treatment (MPH + FLX) during juvenile periods are unknown. We administered saline (VEH), MPH, FLX, or MPH + FLX to juvenile Sprague Dawley male rats from postnatal day 20 to 34, and assessed their reactivity to reward- and mood-related stimuli 24 h or 2 months after drug exposure. We also assessed mRNA and protein levels within the ventral tegmental area (VTA) to determine the effect of MPH, FLX, or MPH + FLX on the extracellular signal-regulated protein kinase-1/2 (ERK) pathway--a signaling cascade implicated in motivation and mood regulation. MPH + FLX enhanced sensitivity to drug (i.e., cocaine) and sucrose rewards, as well as anxiety (i.e., elevated plus maze)- and stress (i.e., forced swimming)-eliciting situations when compared with VEH-treated rats. MPH + FLX exposure also increased mRNA of ERK2 and its downstream targets cAMP response element-binding protein (CREB), BDNF, c-Fos, early growth response protein-1 (Zif268), and mammalian target of rapamycin (mTOR), and also increased protein phosphorylation of ERK2, CREB, and mTOR 2 months after drug exposure when compared with VEH-treated rats. Using herpes simplex virus-mediated gene transfer to block ERK2 activity within the VTA, we rescued the MPH and FLX-induced behavioral deficits seen in the forced-swimming task 2 months after drug treatment. These results indicate that concurrent MPH + FLX exposure during preadolescence increases sensitivity to reward-related stimuli while simultaneously enhancing susceptibility to stressful situations, at least in part, due to long-lasting disruptions in ERK signaling within the VTA.
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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.