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Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy

Kuzhuppilly Ramakrishnan, N., Schepers, M., Luurtsema, G., Nyakas, C. J., Elsinga, P. H., Ishiwata, K., Dierckx, R. A. J. O. & van Waarde, A., Jun-2015, In : Molecular Imaging and Biology. 17, 3, p. 364-372 9 p.

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  • Cutamesine Overcomes REM Sleep Deprivation-Induced

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DOI

Rapid eye movement (REM) sleep deprivation (SD) decreases cerebral sigma-1 receptor expression and causes cognitive deficits. Sigma-1 agonists are cognitive enhancers. Here, we investigate the effect of cutamesine treatment in the REM SD model.

Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([C-11]SA4503) and positron emission tomography (PET), and tissue cutamesine levels were measured by ultra performance liquid chromatography (UPLC)-MS. RO was calculated from a Cunningham-Lassen plot, based on the total distribution volume of [C-11]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test.

Cutamesine at a dose of 1.0 mg/kg reversed REM SD-induced cognitive deficit and occupied 92 % of the sigma-1 receptor population. A lower dose (0.3 mg/kg) occupied 88 % of the receptors but did not significantly improve cognition.

The anti-amnesic effect of cutamesine in this animal model may be related to longer exposure at a higher dose and/or drug binding to secondary targets.

Original languageEnglish
Pages (from-to)364-372
Number of pages9
JournalMolecular Imaging and Biology
Volume17
Issue number3
Publication statusPublished - Jun-2015

    Keywords

  • Sigma-1 receptor, Receptor occupancy, Cutamesine, REM sleep deprivation, Amnesia, Positron emission tomography, Passive avoidance, POSITRON-EMISSION-TOMOGRAPHY, SELECTIVE CHOLINERGIC LESION, COGNITIVE ENHANCER, RAT-BRAIN, BEHAVIORAL EVIDENCE, OBJECT RECOGNITION, INDUCED AMNESIA, MODULATING ROLE, IN-VIVO, SA4503

ID: 15893433