Differential effects of neonatal SSRI treatments on hypoxia-induced behavioral changes in male and female offspring. (30th September 2017)

• Record Type: Journal Article
• Authors: Nagano, Reiko; Nagano, Masatoshi; Nakai, Akihito; Takeshita, Toshiyuki; Suzuki, Hidenori
• Is Part Of: Neuroscience. Volume 360(2017)
• Page Start: 95
• Page End: 105
• Publication Date: 2017-09-30
• Subjects: 5-HIAA 5-hydroxyindole acetic acid -- CS conditioned stimulus -- DA dopamine -- DAT dopamine transporter -- DOPAC 3, 4-dihydroxy-phenylacetic acid -- EPM elevated plus maze -- ESC escitalopram -- FLX fluoxetine -- FST forced swim test -- GD gestational day -- HPLC high-performance liquid chromatography -- NET norepinephrine transporter -- OF open field test -- PFC prefrontal cortex -- PPI prepulse inhibition test -- SERT serotonin transporter -- SSRI selective serotonin reuptake inhibitor -- UAO uterine artery occlusion -- US unconditioned stimulus; prenatal hypoxia -- behavior -- intervention -- serotonin -- dopamine; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.07.051
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Prenatal hypoxia produced differential behavioral changes in male and female offspring. Neonatal fluoxetine, an SSRI, ameliorated the behavioral changes in both males and females. Neonatal escitalopram, an SSRI, ameliorated the behavioral changes only in females. Both SSRIs suppressed the increase in dopamine levels induced by prenatal hypoxia in the female hippocampus. Abstract: Prenatal hypoxia induced by transient intrauterine ischemia is a serious clinical problem, and at present, effective treatments are lacking. Currently, it is unknown how prenatal hypoxia affects behaviors in adulthood. Therefore, we developed a mouse model that mimics prenatal hypoxia in humans using uterine artery occlusion in late gestation. We examined whether prenatal hypoxia induces behavioral changes in adult male and female offspring by conducting a series of behavioral tests. In adulthood, longer immobility was observed in the forced swim test in males, whereas females showed decreased inhibition in the prepulse inhibition test. We then investigated the effects of two different selective serotonin reuptake inhibitors (SSRIs), fluoxetine (FLX) and escitalopram (ESC), on these behavioral changes. These drugs affect the neurodevelopmental process and have long-term neurological consequences. FLX treatment from postnatal day 3 (P3) to P21 ameliorated the behavioral changes in both male and female mice. In comparison, ESC treatment ameliorated the behavioral changes only in female mice. Neurochemical analysis revealed that dopamine was increased in the female hippocampus, but not in males. Thus, neonatal SSRI treatment decreases dopamine levels in the hippocampus in females selectively. Our findings suggest that prenatal hypoxia is a risk factor for behavioral abnormalities in adulthood, and that neonatal SSRI treatment might have clinical potential for alleviating these long-term behavioral deficits.