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.
Highlights
Modafinil is an analeptic medication used clinically in the treatment of narcolepsy, shift work disorder, and daytime somnolence due to sleep apnea without interfering with nocturnal sleep [1,2,3]
Less than 4% intraanimal glutamate chemical exchange saturation transfer (GluCEST) coefficient of variation (CV) was observed from group 4
No observable change in GluCEST contrast was observed up to 5 hours after Modafinil administration. These results are consistent with the results reported from liquid chromatography (HPLC) studies of rodents administered Modafinil [15]
Summary
Modafinil is an analeptic medication used clinically in the treatment of narcolepsy, shift work disorder, and daytime somnolence due to sleep apnea without interfering with nocturnal sleep [1,2,3]. It increases wakening in rodents (Simon et al, 1994; Touret et al, 1995), monkeys (Hermant et al, 1991; Lagarde and Milhaud, 1990) and humans [4]. A 2D COSY MRS study in rat brain has shown that Modafinil increased cerebral Glu level significantly within few hours (2–7 hours) [18]. In another study using high performance liquid chromatography (HPLC) observed an increase in Glu at 12 to 24 hours, but not at 2–7 hours, post Modafinil administration [15]
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