Transient postnatal fluoxetine decreases brain concentrations of 20-HETE and 15-epi-LXA4, arachidonic acid metabolites in adult mice

BackgroundTransient 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).HypothesisBrain 20-hydroxyeicosatetraenoic acid (20-HETE), converted by CYP4A from ARA, will be reduced in adult mice treated transiently and postnatally with fluoxetine.MethodsMale mice pups were injected i.p. daily with fluoxetine (10 mg/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.ResultsPostnatal 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.ConclusionsBehavioral changes in adult mice treated postnatally with fluoxetine may be related to reduced brain ARA metabolism involving CYP4A and 20-HETE formation.