ArticleNeuropharmacology2015
Fluoxetine potentiation of methylphenidate-induced gene regulation in striatal output pathways: potential role for 5-HT1B receptor.
Article in Neuropharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 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
- Chronic Combined Oral Methylphenidate and Fluoxetine Increases Inflammation in Somatosensory and Mesolimbic Brain Regions.Neurochemical research · 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
- Vilazodone, a Novel SSRI Antidepressant with 5-HT1A Partial Agonist Properties: Diminished Potentiation of Chronic Oral Methylphenidate-Induced Dynorphin Expression in the Striatum in Adolescent Male Rats.Molecular neurobiology · 2025Article
- Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024.F1000Research · 2025Article
- Combined Methylphenidate and Selective Serotonin Reuptake Inhibitors in Adults With Attention-Deficit/Hyperactivity Disorder.JAMA network open · 2024Article
- Vilazodone, a Selective Serotonin Reuptake Inhibitor with Diminished Impact on Methylphenidate-Induced Gene Regulation in the Striatum: Role of 5-HT1A Receptor.Molecular neurobiology · 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
- Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders.International journal of molecular sciences · 2023Review
- Phosphodiesterase 10A (PDE10A): Regulator of Dopamine Agonist-Induced Gene Expression in the Striatum.Cells · 2022Article
- Fluoxetine Potentiates Oral Methylphenidate-Induced Gene Regulation in the Rat Striatum.Molecular neurobiology · 2021Article
- Article
- Selective Regulation of 5-HT1B Serotonin Receptor Expression in the Striatum by Dopamine Depletion and Repeated L-DOPA Treatment: Relationship to L-DOPA-Induced Dyskinesias.Molecular neurobiology · 2020Article
- [Research advances in pathogenesis of attention deficit hyperactivity disorder].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2018Article
- The 5-HT1B serotonin receptor regulates methylphenidate-induced gene expression in the striatum: Differential effects on immediate-early genes.Journal of psychopharmacology (Oxford, England) · 2017Article
- Effects of anti-depressant treatments on FADD and p-FADD protein in rat brain cortex: enhanced anti-apoptotic p-FADD/FADD ratio after chronic desipramine and fluoxetine administration.Psychopharmacology · 2016Article
- Potentiated gene regulation by methylphenidate plus fluoxetine treatment: Long-term gene blunting (Basal ganglia · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Drug combinations that include the psychostimulant methylphenidate plus a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine are increasingly used in children and adolescents. For example, this combination is indicated in the treatment of attention-deficit/hyperactivity disorder and depression comorbidity and other mental disorders. Such co-exposure also occurs in patients on SSRIs who use methylphenidate as a cognitive enhancer. The neurobiological consequences of these drug combinations are poorly understood. Methylphenidate alone can produce gene regulation effects that mimic addiction-related gene regulation by cocaine, consistent with its moderate addiction liability. We have previously shown that combining SSRIs with methylphenidate potentiates methylphenidate-induced gene regulation in the striatum. The present study investigated which striatal output pathways are affected by the methylphenidate + fluoxetine combination, by assessing effects on pathway-specific neuropeptide markers, and which serotonin receptor subtypes may mediate these effects. Our results demonstrate that a 5-day repeated treatment with fluoxetine (5 mg/kg) potentiates methylphenidate (5 mg/kg)-induced expression of both dynorphin (direct pathway marker) and enkephalin (indirect pathway). These changes were accompanied by correlated increases in the expression of the 5-HT1B, but not 5-HT2C, serotonin receptor in the same striatal regions. A further study showed that the 5-HT1B receptor agonist CP94253 (3-10 mg/kg) mimics the fluoxetine potentiation of methylphenidate-induced gene regulation. These findings suggest a role for the 5-HT1B receptor in the fluoxetine effects on striatal gene regulation. Given that 5-HT1B receptors are known to facilitate addiction-related gene regulation and behavior, our results suggest that SSRIs may enhance the addiction liability of methylphenidate by increasing 5-HT1B receptor signaling.
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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.