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dc.contributor.authorQuansah, Emmanuelen
dc.contributor.authorRuiz-Rodado, Victoren
dc.contributor.authorGrootveld, M.en
dc.contributor.authorZetterstrom, T. S. C.en
dc.date.accessioned2018-02-27T11:32:39Z
dc.date.available2018-02-27T11:32:39Z
dc.date.issued2018-02-23
dc.identifier.citationQuansah, E., Ruiz-Rodado, V., Grootveld, M. and Zetterstrom, T.S.C. (2018) Methylphenidate alters monoaminergic and metabolic pathways in the cerebellum of adolescent rats. European Neuropsychopharmacologyen
dc.identifier.issn0924-977X
dc.identifier.urihttp://hdl.handle.net/2086/15278
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linken
dc.description.abstractAbnormalities in the cerebellar circuitry have been suggested to contribute to some of the symptoms associated with attention deficit hyperactivity disorder (ADHD). The psychostimulant methylphenidate (MPH) is the major drug for treating this condition. Here, the effects of acute (2.0 mg/kg and 5.0 mg/kg) and chronic (2.0 mg/kg, twice daily for 15 days) MPH treatments were investigated in adolescent (35-40 days old) rats on monoaminergic and metabolic markers in the cerebellum. Data acquired indicates that acute MPH treatment (2.0 mg/kg) decreased cerebellar vesicular monoamine transporter (VMAT2) density, while chronic treatment caused an increase. In contrast, protein levels of tyrosine hydroxylase (TH) and the dopamine D1 receptor were not significantly altered by neither acute nor chronic MPH treatment. In addition, while chronic but not acute MPH treatment significantly enhanced dopamine turnover (DOPAC/dopamine) in the cerebellum, levels of dopamine and homovanillic acid (HVA) were not altered. Acute MPH (5.0 mg/kg) significantly modified levels of a range of cerebellar metabolites with similar trends also detected for the lower dose (2.0 mg/kg). In this regard, acute MPH tended to decrease cerebellar metabolites associated with energy consumption and excitatory neurotransmission including glutamate, glutamine, N-acetyl aspartate, and inosine. Conversely, levels of some metabolites associated with inhibitory neurotransmission, including GABA and glycine were reduced by acute (5.0 mg/kg) MPH, together with acetate, aspartate and hypoxanthine. In conclusion, this study demonstrated that MPH alters cerebellar biochemistry, and that this effect depends on both dose and duration of treatment. The therapeutic significance of these results requires further investigation.en
dc.language.isoenen
dc.publisherElsevieren
dc.subject1H-NMRen
dc.subjectADHDen
dc.subjectMethylphenidateen
dc.subjectCerebellumen
dc.subjectGABAen
dc.subjectGlutamateen
dc.titleMethylphenidate alters monoaminergic and metabolic pathways in the cerebellum of adolescent ratsen
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.1016/j.euroneuro.2018.02.002
dc.researchgroupPharmacologyen
dc.peerreviewedYesen
dc.funderN/Aen
dc.projectidN/Aen
dc.cclicenceCC-BY-NCen
dc.date.acceptance2018-02-07en
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en


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