title: Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice.
abstract: BACKGROUND
  Transient postnatal exposure of rodents to the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine alters behavior and brain 5-HT neurotransmission during adulthood, and also reduces brain arachidonic (ARA) metabolic consumption and protein level of the ARA metabolizing enzyme, cytochrome P4504A (CYP4A).
  
  
  OBJECTIVE
  Brain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine.
  
  
  METHODS
  Male mice pups were injected i.p. daily with fluoxetine (10mg/kg) or saline during P4-P21. At P90 their brain was high-energy microwaved and analyzed for 20-HETE and six other ARA metabolites by enzyme immunoassay.
  
  
  RESULTS
  Postnatal fluoxetine vs. saline significantly decreased brain concentrations of 20-HETE (-70.3%) and 15-epi-lipoxin A4 (-60%) in adult mice, but did not change other eicosanoid concentrations.
  
  
  CONCLUSIONS
  Behavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation.
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Yuan
authors.affiliation: Brain Physiology and Metabolism Section, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. Electronic address: sir@mail.nih.gov.
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000032:analysis*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D005473:Fluoxetine / Q000008:administration & dosage* / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis*; D007274:Injections, Intraperitoneal; D044045:Lipoxins / Q000032:analysis*; D008297:Male; D051379:Mice; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D001095:Arachidonic Acids; D005473:Fluoxetine; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D017367:Selective Serotonin Reuptake Inhibitors; C040527:lipoxin A4; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid
keywords: 15-epi-LXA4; 20-HETE; 5-HT; Arachidonic; Brain; Fluoxetine