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dc.contributor.authorQuansah, Emmanuelen
dc.contributor.authorRuiz-Rodado, Victoren
dc.contributor.authorGrootveld, M.en
dc.contributor.authorProbert, Fayen
dc.contributor.authorZetterstrom, T. S. C.en
dc.date.accessioned2017-03-28T14:35:29Z
dc.date.available2017-03-28T14:35:29Z
dc.date.issued2017-03-06
dc.identifier.citationQuansah, E., Ruiz-Rodado, V., Grootveld, M., Probert, F. and Zetterström, T.S. (2017) 1H NMR-based metabolomics reveals neurochemical alterations in the brain of adolescent rats following acute methylphenidate administration. Neurochemistry International, 108, pp. 109-120en
dc.identifier.otherPMID 28268188
dc.identifier.urihttp://hdl.handle.net/2086/13923
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 link.en
dc.description.abstractThe psychostimulant methylphenidate (MPH) is increasingly used in the treatment of attention deficit hyperactivity disorder (ADHD). While there is little evidence for common brain pathology in ADHD, some studies suggest a right hemisphere dysfunction among people diagnosed with the condition. However, in spite of the high usage of MPH in children and adolescents, its mechanism of action is poorly understood. Given that MPH blocks the neuronal transporters for dopamine and noradrenaline, most research into the effects of MPH on the brain has largely focused on these two monoamine neurotransmitter systems. Interestingly, recent studies have demonstrated metabolic changes in the brain of ADHD patients, but the impact of MPH on endogenous brain metabolites remains unclear. In this study, a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach was employed to investigate the effects of MPH on brain biomolecules. Adolescent male Sprague Dawley rats were injected intraperitoneally with MPH (5.0 mg/kg) or saline (1.0 ml/kg), and cerebral extracts from the left and right hemispheres were analysed. A total of 22 variables (representing 13 distinct metabolites) were significantly increased in the MPH-treated samples relative to the saline-treated controls. The upregulated metabolites included: amino acid neurotransmitters such as GABA, glutamate and aspartate; large neutral amino acids (LNAA), including the aromatic amino acids (AAA) tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline; and metabolites associated with energy and cell membrane dynamics, such as creatine and myo-inositol. No significant differences in metabolite concentrations were found between the left and right cerebral hemispheres. These findings provide new insights into the mechanisms of action of the anti-ADHD drug MPH.en
dc.publisherElsevieren
dc.subjectMethylphenidateen
dc.subjectADHDen
dc.subject1H-NMRen
dc.subjectCerebral hemispheresen
dc.subjectGABAen
dc.subjectTyrosineen
dc.title1H NMR-based metabolomics reveals neurochemical alterations in the brain of adolescent rats following acute methylphenidate administrationen
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.1016/j.neuint.2017.03.003
dc.researchgroupPharmacologyen
dc.peerreviewedYesen
dc.funderN/Aen
dc.projectidN/Aen
dc.cclicenceCC-BY-NC-NDen
dc.date.acceptance2017-03-03en
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en


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