title: Altered sleep and affect in the neurotensin receptor 1 knockout mouse.
abstract: OBJECTIVE
  Sleep and mood disorders have long been understood to have strong genetic components, and there is considerable comorbidity of sleep abnormalities and mood disorders, suggesting the involvement of common genetic pathways. Here, we examine a candidate gene implicated in the regulation of both sleep and affective behavior using a knockout mouse model.
  
  
  METHODS
  Previously, we identified a quantitative trait locus (QTL) for REM sleep amount, REM sleep bout number, and wake amount in a genetically segregating population of mice. Here, we show that traits mapping to this QTL correlated with an expression QTL for neurotensin receptor 1 (Ntsr1), a receptor for neurotensin, a ligand known to be involved in several psychiatric disorders. We examined sleep as well as behaviors indicative of anxiety and depression in the NTSR1 knockout mouse.
  
  
  RESULTS
  NTSR1 knockouts had a lower percentage of sleep time spent in REM sleep in the dark phase and a larger diurnal variation in REM sleep duration than wild types under baseline conditions. Following sleep deprivation, NTSR1 knockouts exhibited more wake and less NREM rebound sleep. NTSR1 knockouts also showed increased anxious and despair behaviors.
  
  
  CONCLUSIONS
  Here we illustrate a link between expression of the Ntsr1 gene and sleep traits previously associated with a particular QTL. We also demonstrate a relationship between Ntsr1 and anxiety and despair behaviors. Given the considerable evidence that anxiety and depression are closely linked with abnormalities in sleep, the data presented here provide further evidence that neurotensin and Ntsr1 may be a component of a pathway involved in both sleep and mood disorders.
authors: Center for Sleep and Circadian Biology, Northwestern University, Evanston, IL, USA.
authors: Karrie
authors: K
authors: Fitzpatrick
authors: Christopher J
authors: CJ
authors: Winrow
authors: Anthony L
authors: AL
authors: Gotter
authors: Joshua
authors: J
authors: Millstein
authors: Janna
authors: J
authors: Arbuzova
authors: Joseph
authors: J
authors: Brunner
authors: Andrew
authors: A
authors: Kasarskis
authors: Martha H
authors: MH
authors: Vitaterna
authors: John J
authors: JJ
authors: Renger
authors: Fred W
authors: FW
authors: Turek
mesh_terms: D000339:Affect / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000235:genetics; D003863:Depression / Q000235:genetics; D004569:Electroencephalography; D004576:Electromyography; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D040641:Quantitative Trait Loci; D018028:Receptors, Neurotensin / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology
chemical_list: D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor