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dc.contributor.author
Michaelides, Michael
dc.contributor.author
Pascau, Javier
dc.contributor.author
Gispert, Juan Domingo
dc.contributor.author
Delis, Foteini
dc.contributor.author
Grandy, David K.
dc.contributor.author
Wang, Gene Jack
dc.contributor.author
Desco, Manuel
dc.contributor.author
Rubinstein, Marcelo
dc.contributor.author
Volkow, Nora D.
dc.contributor.author
Thanos, Panayotis K.
dc.date.available
2019-07-15T20:32:07Z
dc.date.issued
2010-08
dc.identifier.citation
Michaelides, Michael; Pascau, Javier; Gispert, Juan Domingo; Delis, Foteini; Grandy, David K.; et al.; Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate; Wiley Blackwell Publishing, Inc; European Journal Of Neuroscience; 32; 4; 8-2010; 668-676
dc.identifier.issn
0953-816X
dc.identifier.uri
http://hdl.handle.net/11336/79581
dc.description.abstract
Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D4) 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 [18F]2-fluoro- 2-deoxy-d-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D4. Images were analyzed using a novel automated image registration procedure. Baseline D4 -/- mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D4 +/+ and D4 +/- mice; when given MP, D 4 -/- mice increased metabolism in the PFC and decreased it in the CBV, whereas in D4 +/+ and D4 +/- 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 D4 polymorphisms.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley Blackwell Publishing, Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
2-[18f]-Fluoro-2-Deoxy-D-Glucose
dc.subject
Attention Deficit Hyperactivity Disorder
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Mice
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Micro-Positron Emission Tomography
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Positron Emission Tomography
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-07-10T19:05:08Z
dc.journal.volume
32
dc.journal.number
4
dc.journal.pagination
668-676
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Michaelides, Michael. Brookhaven National Laboratory; Estados Unidos. Stony Brook University; Estados Unidos
dc.description.fil
Fil: Pascau, Javier. Hospital General Universitario Gregorio Marañon; España
dc.description.fil
Fil: Gispert, Juan Domingo. Institut D’Alta Tecnologia; España
dc.description.fil
Fil: Delis, Foteini. Laboratory of Neuroimaging; Estados Unidos
dc.description.fil
Fil: Grandy, David K.. Oregon Health Sciences University; Estados Unidos
dc.description.fil
Fil: Wang, Gene Jack. Laboratory of Neuroimaging; Estados Unidos
dc.description.fil
Fil: Desco, Manuel. Hospital General Universitario Gregorio Marañon; España
dc.description.fil
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
dc.description.fil
Fil: Volkow, Nora D.. Laboratory of Neuroimaging; Estados Unidos
dc.description.fil
Fil: Thanos, Panayotis K.. Brookhaven National Laboratory; Estados Unidos. Institut D’Alta Tecnologia; España. Laboratory of Neuroimaging; Estados Unidos
dc.journal.title
European Journal Of Neuroscience
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1111/j.1460-9568.2010.07319.x
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1460-9568.2010.07319.x
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