High resolution mapping of Modafinil induced changes in glutamate level in rat brain

Mohammad Haris, Anup Singh, Kejia Cai, Kavindra Nath, Gaurav Verma, Ravi Prakash Reddy Nanga, Hari Hariharan, John A. Detre, Neill Epperson, Ravinder Reddy

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Abstract

Modafinil is marketed in the United States for the treatment of narcolepsy and daytime somnolence due to shift-work or sleep apnea. Investigations of this drug in the treatment of cocaine and nicotine dependence in addition to disorders of executive function are also underway. Modafinil has been known to increase glutamate levels in rat brain models. Proton magnetic resonance spectroscopy (1HMRS) has been commonly used to detect the glutamate (Glu) changes in vivo. In this study, we used a recently described glutamate chemical exchange saturation transfer (GluCEST) imaging technique to measure Modafinil induced regional Glu changes in rat brain and compared the results with Glu concentration measured by single voxel 1HMRS. No increases in either GluCEST maps or 1HMRS were observed after Modafinil injection over a period of 5 hours. However, a significant increase in GluCEST (19±4.4%) was observed 24 hours post Modafinil administration, which is consistent with results from previous biochemical studies. This change was not consistently seen with 1HMRS. GluCEST mapping allows regional cerebral Glu changes to be measured and may provide a useful clinical biomarker of Modafinil effects for the management of patients with sleep disorders and addiction.

Original languageEnglish
Article numbere103154
JournalPloS one
Volume9
Issue number7
DOIs
Publication statusPublished - 28 Jul 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Haris, M., Singh, A., Cai, K., Nath, K., Verma, G., Nanga, R. P. R., Hariharan, H., Detre, J. A., Epperson, N., & Reddy, R. (2014). High resolution mapping of Modafinil induced changes in glutamate level in rat brain. PloS one, 9(7), [e103154]. https://doi.org/10.1371/journal.pone.0103154