title: Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, Netherlands.
authors.forename: Nisha K
authors.initials: NK
authors.lastname: Ramakrishnan
authors.forename: Marianne
authors.initials: M
authors.lastname: Schepers
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.forename: Csaba J
authors.initials: CJ
authors.lastname: Nyakas
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.forename: Aren
authors.initials: A
authors.lastname: van Waarde
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015283:Citalopram / Q000627:therapeutic use; D003071:Cognition; D008297:Male; D013058:Mass Spectrometry; D008569:Memory Disorders / Q000188:drug therapy*; D010879:Piperazines / Q000737:chemistry; D049268:Positron-Emission Tomography; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000819:agonists*; D012892:Sleep Deprivation / Q000188:drug therapy*; D012895:Sleep, REM / Q000187:drug effects*; D000097605:Sigma-1 Receptor
chemical_list: D015283:Citalopram; D010879:Piperazines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C101789:SA 4503