1H NMR-based metabolomics reveals neurochemical alterations in the brain of adolescent rats following acute methylphenidate administration
| Autor: | Martin Grootveld, Tyra S.C. Zetterström, Fay Probert, Emmanuel Quansah, Victor Ruiz-Rodado |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Metabolite Pharmacology Creatine GABA 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Neurochemical Dopamine mental disorders medicine ADHD Methylphenidate 1H-NMR Glutamate receptor Cell Biology 030104 developmental biology Monoamine neurotransmitter chemistry Cerebral hemispheres Tyrosine NMDA receptor Psychology human activities Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurochemistry International. 108:109-120 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2017.03.003 |
| Popis: | The 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. The 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. |
| Databáze: | OpenAIRE |
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