ArticleThe European journal of neuroscience2010
Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate.
Article in The European journal of neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Novel dopamine 4 receptor ligands differentially ameliorate ADHD-like behaviors in spontaneously hypertensive rats.Psychopharmacology · 2026Article
- Cross-talk between dopamine and noradrenaline modulates glutamatergic transmission in the deep cerebellar nuclei.Scientific reports · 2025Article
- Effects of Methylphenidate on the Dopamine Transporter and Beyond.Current topics in behavioral neurosciences · 2022Article
- Synaptic ZnTranslational psychiatry · 2021Article
- DRD4 Mitigates Myocardial Ischemia/Reperfusion Injury in Association With PI3K/AKT Mediated Glucose Metabolism.Frontiers in pharmacology · 2020Article
- PharmGKB summary: methylphenidate pathway, pharmacokinetics/pharmacodynamics.Pharmacogenetics and genomics · 2019Review
- The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities.Neuroscience and biobehavioral reviews · 2018Review
- Acute engagement of GMolecular psychiatry · 2018Article
- Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Article
- Roux-en-Y Gastric Bypass Alters Brain Activity in Regions that Underlie Reward and Taste Perception.PloS one · 2015Article
- Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks.The Journal of clinical investigation · 2013Article
- Dopamine, cognitive function, and gamma oscillations: role of D4 receptors.Frontiers in cellular neuroscience · 2013Article
- Functional Recovery after Scutellarin Treatment in Transient Cerebral Ischemic Rats: A Pilot Study with (18) F-Fluorodeoxyglucose MicroPET.Evidence-based complementary and alternative medicine : eCAM · 2013Article
- Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.PloS one · 2013Article
- The influence of dopamine receptor d4 polymorphism on resting EEG in healthy young females.The open neuroimaging journal · 2012Article
- Dopamine D₄ receptor activation controls circadian timing of the adenylyl cyclase 1/cyclic AMP signaling system in mouse retina.The European journal of neuroscience · 2011Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D(4)) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [(18)F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D(4). Images were analyzed using a novel automated image registration procedure. Baseline D(4)(-/-) mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D(4)(+/+) and D(4)(+/-) mice; when given MP, D(4)(-/-) mice increased metabolism in the PFC and decreased it in the CBV, whereas in D(4)(+/+) and D(4)(+/-) mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D(4) polymorphisms.
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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.