title: Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.
abstract: BACKGROUND
  Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs - also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated.
  
  
  METHODS
  The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB).
  
  
  RESULTS
  The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment.
  
  
  CONCLUSIONS
  The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.
authors.affiliation: a Department of Neurophysiology and Neuropharmacology , Center for Pharmacology and Physiology, Medical University of Vienna , Vienna , Austria ;
authors.forename: Jörg
authors.initials: J
authors.lastname: Schaufler
authors.affiliation: a Department of Neurophysiology and Neuropharmacology , Center for Pharmacology and Physiology, Medical University of Vienna , Vienna , Austria ;
authors.forename: Marianne
authors.initials: M
authors.lastname: Ronovsky
authors.affiliation: a Department of Neurophysiology and Neuropharmacology , Center for Pharmacology and Physiology, Medical University of Vienna , Vienna , Austria ;
authors.forename: Giorgia
authors.initials: G
authors.lastname: Savalli
authors.affiliation: a Department of Neurophysiology and Neuropharmacology , Center for Pharmacology and Physiology, Medical University of Vienna , Vienna , Austria ;
authors.forename: Maureen
authors.initials: M
authors.lastname: Cabatic
authors.affiliation: b Department of Pharmacology and Toxicology , Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck , Innsbruck , Austria.
authors.forename: Simone B
authors.initials: SB
authors.lastname: Sartori
authors.affiliation: b Department of Pharmacology and Toxicology , Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck , Innsbruck , Austria.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Singewald
authors.affiliation: a Department of Neurophysiology and Neuropharmacology , Center for Pharmacology and Physiology, Medical University of Vienna , Vienna , Austria ;
authors.forename: Daniela D
authors.initials: DD
authors.lastname: Pollak
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D056931:Cryptochromes / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008027:Light; D051379:Mice; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000071218:Ultradian Rhythm / Q000187:drug effects*
chemical_list: D056931:Cryptochromes; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; C538967:Cry2 protein, mouse
keywords: Anxiety disorders; circadian rhythm; clock genes; depression; fluoxetine; hippocampus; mouse model