title: High resolution mapping of modafinil induced changes in glutamate level in rat brain.
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.
authors: CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors: Mohammad
authors: M
authors: Haris
authors: CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Center for Biomedical Engineering, Indian Institute of Technology Delhi, Delhi, India.
authors: Anup
authors: A
authors: Singh
authors: CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; CMRR, Radiology, University of Illinois at Chicago, Chicago, Illinois, United States of America.
authors: Kejia
authors: K
authors: Cai
authors: Molecular Imaging, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Kavindra
authors: K
authors: Nath
authors: Molecular Imaging, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Gaurav
authors: G
authors: Verma
authors: CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Ravi Prakash Reddy
authors: RP
authors: Nanga
authors: CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Hari
authors: H
authors: Hariharan
authors: CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: John A
authors: JA
authors: Detre
authors: Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Neill
authors: N
authors: Epperson
authors: CMROI, Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Ravinder
authors: R
authors: Reddy
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D001931:Brain Mapping; D018698:Glutamic Acid / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D000077408:Modafinil; D057054:Molecular Imaging; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D013997:Time Factors; D064690:Wakefulness-Promoting Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D018698:Glutamic Acid; D000077408:Modafinil