Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice.

Journal of Nutrition and Metabolism
Gary J KummetRobert D Roghair

Abstract

Background. Selective serotonin reuptake inhibitor (SSRI) therapy complicates up to 10% of pregnancies. During therapy, SSRIs exert pleiotropic antidepressant, anorexigenic, and neurotrophic effects. Intrauterine SSRI exposure has been modeled by neonatal administration to developmentally immature rodents, and it has paradoxically elicited features of adult depression. We hypothesized neonatal SSRI exposure likewise programs a rebound hypermetabolic state in adult mice. Methods. C57BL/6 pups were randomized to saline or sertraline (5 mg/kg/d) from P1-P14. Because estrogen increases tryptophan hydroxylase 2 (TPH2) expression, a subset of female mice underwent sham surgery or bilateral ovariectomy (OVX). Metabolic rate was determined by indirect calorimetry. Results. In both male and female mice, neonatal SSRI exposure increased adult caloric intake and metabolic rate. SSRI-exposed female mice had significantly decreased adult weight with a relative increase in brain weight and melatonin excretion, independent of ovarian status. Cerebral cortex TPH2 expression was increased in SSRI-exposed male mice but decreased in OVX SSRI-exposed female mice. Conclusions. SSRI exposure during a critical neurodevelopmental window increases adul...Continue Reading

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Citations

Aug 8, 2013·Journal of Cardiovascular Pharmacology·Sarah E HaskellRobert D Roghair
Aug 20, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Lígia Cristina Monteiro GalindoRaul Manhães de Castro
Jan 30, 2014·Behavioural Brain Research·Benjamin C DexterRobert D Roghair
Apr 8, 2017·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Lauritz R MeyerSarah E Haskell
Dec 13, 2012·Pediatric Research·Sarah E HaskellRobert D Roghair
Sep 18, 2020·Canadian Journal of Physiology and Pharmacology·Raquel de Medeiros Maia CamposRaul Manhães-de-Castro
Jun 12, 2018·European Journal of Pharmacology·Manuella da L D BarrosLigia Galindo

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bilateral
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SigmaPlot

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