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

Nisha Kuzhuppilly Ramakrishnan, Marianne Schepers, Gert Luurtsema, Csaba J. Nyakas, Philip H. Elsinga, Kiichi Ishiwata, Rudi A. J. O. Dierckx, Aren van Waarde*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)364-372
Number of pages9
JournalMolecular Imaging and Biology
Volume17
Issue number3
DOIs
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

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