Abstract
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 language | English |
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Pages (from-to) | 364-372 |
Number of pages | 9 |
Journal | Molecular Imaging and Biology |
Volume | 17 |
Issue number | 3 |
DOIs | |
Publication status | Published - 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