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

Abstract

PURPOSE:

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.

PROCEDURES:

Sigma-1 receptor occupancy (RO) in the rat brain by cutamesine was determined using 1-[2-(3,4-dimethoxyphenethyl)]-4-(3-phenylpropyl)piperazine ([(11)C]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 [(11)C]SA4503 determined by Logan graphical analysis. Cognitive performance was assessed using the passive avoidance (PA) test.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Nisha K Ramakrishnan, Marianne Schepers, Gert Luurtsema, Csaba J Nyakas, Philip H Elsinga, Kiichi Ishiwata, Rudi A J O Dierckx, Aren van Waarde
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 17 Issue 3 Pg. 364-72 (Jun 2015) ISSN: 1860-2002 [Electronic] United States
• PMID: 25449772 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Receptors, sigma
• sigma-1 receptor
• Citalopram
• SA 4503

Topics

• Animals
• Brain (diagnostic imaging, metabolism)
• Chromatography, High Pressure Liquid (methods)
• Citalopram (therapeutic use)
• Cognition
• Male
• Mass Spectrometry
• Memory Disorders (drug therapy)
• Piperazines (chemistry)
• Positron-Emission Tomography
• Protein Binding
• Rats
• Rats, Wistar
• Receptors, sigma (agonists)
• Sleep Deprivation (drug therapy)
• Sleep, REM (drug effects)