[en] A significant number of women suffer from depression during pregnancy and the postpartum period. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat maternal depression. While maternal stress and depression have long-term effects on the physical and behavioural development of offspring, numerous studies also point to a significant action of developmental exposure to SSRIs. Surprisingly, preclinical data are limited concerning the combined effect of maternal depression and maternal SSRI exposure on neurobehavioural outcomes in offspring. Therefore, the aim of the present study was to determine how maternal fluoxetine treatment affects the developing HPA system of adolescent male and female offspring using a model of maternal adversity. To do this, gestationally stressed and non-stressed Sprague-Dawley rat dams were chronically treated throughout lactation with either fluoxetine (5mg/kg/day) or vehicle. Four groups of male and female adolescent offspring were used: (1) Prenatal Stress+Fluoxetine, (2) Prenatal Stress+Vehicle, (3) Fluoxetine alone, and (4) Vehicle alone. Primary results show that developmental fluoxetine exposure, regardless of prenatal stress, decreases circulating levels of corticosterone and reduces the expression of the glucocorticoid receptor (GR), and its coactivator the GR interacting protein (GRIP1), in the hippocampus. Interestingly, these effects occurred primarily in male, and not in female, adolescent offspring. Together, these results highlight a marked sex difference in the long-term effect of developmental exposure to SSRI medications that may differentially alter the capacity of the hippocampus to respond to stress.
Disciplines :
Neurology
Author, co-author :
Pawluski, Jodi ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Rayen, Ine
Niessen, Neville-Andrew ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Kristensen, Stephanie
van Donkelaar, Eva L.
Balthazart, Jacques ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Steinbusch, Harry W.M.
Charlier, Thierry ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Language :
English
Title :
Developmental fluoxetine exposure differentially alters central and peripheral measures of the HPA system in adolescent male and female offspring.
Alahmed S., Herbert J. Strain differences in proliferation of progenitor cells in the dentate gyrus of the adult rat and the response to fluoxetine are dependent on corticosterone. Neuroscience 2008, 157:677-682.
Andrews M.H., Matthews S.G. Programming of the hypothalamo-pituitary-adrenal axis: serotonergic involvement. Stress 2004, 7:15-27.
Atkinson H.C., Waddell B.J. Circadian variation in basal plasma corticosterone and adrenocorticotropin in the rat: sexual dimorphism and changes across the estrous cycle. Endocrinology 1997, 138:3842-3848.
Barden N., Reul J.M., Holsboer F. Do antidepressants stabilize mood through actions on the hypothalamic-pituitary-adrenocortical system?. Trends Neurosci 1995, 18:6-11.
Brennan P.A., Pargas R., Walker E.F., Green P., Newport D.J., Stowe Z. Maternal depression and infant cortisol: influences of timing, comorbidity and treatment. J Child Psychol Psychiatry 2008, 49:1099-1107.
Cabrera-Vera T.M., Garcia F., Pinto W., Battaglia G. Effect of prenatal fluoxetine (Prozac) exposure on brain serotonin neurons in prepubescent and adult male rat offspring. J Pharmacol Exp Ther 1997, 280:138-145.
Charlier T.D. Importance of steroid receptor coactivators in the modulation of steroid action on brain and behavior. Psychoneuroendocrinology 2009, 34(Suppl 1):S20-29.
Clinchy M., Zanette L., Charlier T.D., Newman A.E., Schmidt K.L., Boonstra R., Soma K.K. Multiple measures elucidate glucocorticoid responses to environmental variation in predation threat. Oecologia 2011, 166:607-614.
Cooper W.O., Willy M.E., Pont S.J., Ray W.A. Increasing use of antidepressants in pregnancy. AmJ Obstet Gynecol 2007, 196(544):e541-545.
Darnaudery M., Maccari S. Epigenetic programming of the stress response in male and female rats by prenatal restraint stress. Brain Res Rev 2008, 57:571-585.
Davidson J.S., Bolland M.J., Croxson M.S., Chiu W., Lewis J.G. A case of low cortisol-binding globulin: use of plasma free cortisol in interpretation of hypothalamic-pituitary-adrenal axis tests. Ann Clin Biochem 2006, 43:237-239.
Duchesne A., Dufresne M.M., Sullivan R.M. Sex differences in corticolimbic dopamine and serotonin systems in the rat and the effect of postnatal handling. Prog Neuro-psychopharmacol Biol Psychiatry 2009, 33:251-261.
Epperson C.N., Jatlow P.I., Czarkowski K., Anderson G.M. Maternal fluoxetine treatment in the postpartum period: effects on platelet serotonin and plasma drug levels in breastfeeding mother-infant pairs. Pediatrics 2003, 112:e425.
Erdeljan P., Andrews M.H., MacDonald J.F., Matthews S.G. Glucocorticoids and serotonin alter glucocorticoid receptor mRNA levels in fetal guinea-pig hippocampal neurons, in vitro. Reprod Fertil Dev 2005, 17:743-749.
Erdeljan P., MacDonald J.F., Matthews S.G. Glucocorticoids and serotonin alter glucocorticoid receptor (GR) but not mineralocorticoid receptor (MR) mRNA levels in fetal mouse hippocampal neurons, in vitro. Brain Res 2001, 896:130-136.
Field T., Diego M., Hernandez-Reif M. Prenatal depression effects on the fetus and newborn: a review. Infant Behav Dev 2006, 29:445-455.
Field T., Diego M., Hernandez-Reif M., Vera Y., Gil K., Schanberg S., Kuhn C., Gonzalez-Garcia A. Prenatal maternal biochemistry predicts neonatal biochemistry. Int J Neurosci 2004, 114:933-945.
Frieder B., Grimm V.E. Some long-lasting neurochemical effects of prenatal or early postnatal exposure to diazepam. J Neurochem 1985, 45:37-42.
Galea L., McEwen B.S., Tanapat P., Deak T., Spencer R.L., Dhabhar F.S. Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress. Neuroscience 1997, 81:689-697.
Gentile S. The safety of newer antidepressants in pregnancy and breastfeeding. Drug Saf 2005, 28:137-152.
Glover V., O'Connor T.G., O'Donnell K. Prenatal stress and the programming of the HPA axis. Neurosci Biobehav Rev 2010, 35:17-22.
Green M.K., Rani C.S., Joshi A., Soto-Pina A.E., Martinez P.A., Frazer A., Strong R., Morilak D.A. Prenatal stress induces long term stress vulnerability, compromising stress response systems in the brain and impairing extinction of conditioned fear after adult stress. Neuroscience 2011, 192:438-451.
Grenier J., Trousson A., Chauchereau A., Cartaud J., Schumacher M., Massaad C. Differential recruitment of p160 coactivators by glucocorticoid receptor between Schwann cells and astrocytes. Mol Endocrinol 2006, 20:254-267.
Hammond G.L., Lahteenmaki P.L. A versatile method for the determination of serum cortisol binding globulin and sex hormone binding globulin binding capacities. Clin Chim Acta 1983, 132:101-110.
Hamrahian A.H., Oseni T.S., Arafah B.M. Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004, 350:1629-1638.
Harris A., Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav 2011, 59:279-289.
Hendrick V., Stowe Z.N., Altshuler L.L., Mintz J., Hwang S., Hostetter A., Suri R., Leight K., Fukuchi A. Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk. BiolPsychiatry 2001, 50:775-782.
Hong H., Kohli K., Garabedian M.J., Stallcup M.R. GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors. Mol Cell Biol 1997, 17:2735-2744.
Hong H., Kohli K., Trivedi A., Johnson D.L., Stallcup M.R. GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors. Proc Natl Acad Sci U S A 1996, 93:4948-4952.
Ishiwata H., Shiga T., Okado N. Selective serotonin reuptake inhibitor treatment of early postnatal mice reverses their prenatal stress-induced brain dysfunction. Neuroscience 2005, 133:893-901.
Kapoor A., Matthews S.G. Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle. Endocrinology 2008, 149:6406-6415.
Kudielka B.M., Kirschbaum C. Sex differences in HPA axis responses to stress: a review. Biol Psychol 2005, 69:113-132.
Laplante P., Diorio J., Meaney M.J. Serotonin regulates hippocampal glucocorticoid receptor expression via a 5-HT7 receptor. Brain Res Dev Brain Res 2002, 139:199-203.
le Roux C.W., Sivakumaran S., Alaghband-Zadeh J., Dhillo W., Kong W.M., Wheeler M.J. Free cortisol index as a surrogate marker for serum free cortisol. Ann Clin Biochem 2002, 39:406-408.
Levine S. Developmental determinants of sensitivity and resistance to stress. Psychoneuroendocrinology 2005, 30:939-946.
Li H., Kim J.H., Koh S.S., Stallcup M.R. Synergistic effects of coactivators GRIP1 and beta-catenin on gene activation: cross-talk between androgen receptor and Wnt signaling pathways. J Biol Chem 2004, 279:4212-4220.
Lupien S.J., McEwen B.S., Gunnar M.R., Heim C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 2009, 10:434-445.
Maccari S., Darnaudery M., Morley-Fletcher S., Zuena A.R., Cinque C., Van Reeth O. Prenatal stress and long-term consequences: implications of glucocorticoid hormones. Neurosci Biobehav Rev 2003, 27:119-127.
Margarinos A., McEwen B. Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticosteroneicoid secretion and excitatory amino acid receptors. Neuroscience 1995, 69:89-98.
Mastorci F., Vicentini M., Viltart O., Manghi M., Graiani G., Quaini F., Meerlo P., Nalivaiko E., Maccari S., Sgoifo A. Long-term effects of prenatal stress: changes in adult cardiovascular regulation and sensitivity to stress. Neurosci Biobehav Rev 2009, 33:191-203.
McCormick C.M., Mathews I.Z. HPA function in adolescence. Role of sex hormones in its regulation and the enduring consequences of exposure to stressors. Pharmacol Biochem Behav 2007, 86:220-233.
McEwen B.S. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 2008, 583:174-185.
McEwen B.S., Cameron H., Chao H.M., Gould E., Magarinos A.M., Watanabe Y., Woolley C.S. Adrenal steroids and plasticity of hippocampal neurons: toward an understanding of underlying cellular and molecular mechanisms. Cell Mol Neurobiol 1993, 13:457-482.
Meaney M.J., Diorio J., Francis D., LaRocque S., O'Donnell D., Smythe J.W., Sharma S., Tannenbaum B. Environmental regulation of the development of glucocorticoid receptor systems in the rat forebrain. The role of serotonin. Ann N Y Acad Sci 1994, 746:260-273. discussion 274, 289-293.
Mitchell J.B., Iny L.J., Meaney M.J. The role of serotonin in the development and environmental regulation of type II corticosteroid receptor binding in rat hippocampus. Brain Res Dev Brain Res 1990, 55:231-235.
Morrison J.L., Riggs K.W., Chien C., Gruber N., McMillen I.C., Rurak D.W. Chronic maternal fluoxetine infusion in pregnant sheep: effects on the maternal and fetal hypothalamic-pituitary-adrenal axes. Pediatr Res 2004, 56:40-46.
Niessen N.A., Balthazart J., Ball G.F., Charlier T.D. Steroid receptor coactivator 2 (SRC-2) modulates steroid-dependent male sexual behavior and neuroplasticity in Japanese Quail (Coturnix Japonica). J Neurochem 2011.
O'Mahony S.M., Myint A.M., van den Hove D., Desbonnet L., Steinbusch H., Leonard B.E. Gestational stress leads to depressive-like behavioural and immunological changes in the rat. Neuroimmunomodulation 2006, 13:82-88.
Oberlander T.F., Eckstein Grunau R., Fitzgerald C., Ellwood A.L., Misri S., Rurak D., Riggs K.W. Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response. Pediatr Res 2002, 51:443-453.
Oberlander T.F., Grunau R., Mayes L., Riggs W., Rurak D., Papsdorf M., Misri S., Weinberg J. Hypothalamic-pituitary-adrenal (HPA) axis function in 3-month old infants with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure. Early Hum Dev 2008, 84:689-697.
Oberlander T.F., Grunau R.E., Fitzgerald C., Papsdorf M., Rurak D., Riggs W. Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 2005, 115:411-425.
Oberlander T.F., Warburton W., Misri S., Aghajanian J., Hertzman C. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry 2006, 63:898-906.
Oberlander T.F., Weinberg J., Papsdorf M., Grunau R., Misri S., Devlin A.M. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 2008, 3:97-106.
Oliveira E., Pinheiro C.R., Santos-Silva A.P., Trevenzoli I.H., Abreu-Villaca Y., Nogueira Neto J.F., Reis A.M., Passos M.C., Moura E.G., Lisboa P.C. Nicotine exposure affects mother's and pup's nutritional, biochemical, and hormonal profiles during lactation in rats. J Endocrinol 2010, 205:159-170.
Olivier J.D., Blom T., Arentsen T., Homberg J.R. The age-dependent effects of selective serotonin reuptake inhibitors in humans and rodents: A review. Prog Neuro-Psychopharmacol Biol Psychiatry 2011, 35:1400-1408.
Olivier J.D., Valles A., van Heesch F., Afrasiab-Middelman A., Roelofs J.J., Jonkers M., Peeters E.J., Korte-Bouws G.A., Dederen J.P., Kiliaan A.J., Martens G.J., Schubert D., Homberg J.R. Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring. Psychopharmacology 2011, 217:419-432.
Pawluski JL (in press) Perinatal selective serotonin reuptake inhibitor exposure: impact on brain development and neural plasticity. Neuroendocrinology. [Epub ahead of print].
Pawluski J.L., Charlier T.D., Fillet M., Houbart V., Crispin H.T., Steinbusch H.W., van den Hove D.L. Chronic fluoxetine treatment and maternal adversity differentially alter neurobehavioral outcomes in the rat dam. Behav Brain Res 2012, 228:159-168.
Pawluski J.L., Charlier T.D., Lieblich S.E., Hammond G.L., Galea L.A. Reproductive experience alters corticosterone and CBG levels in the rat dam. Physiol Behav 2009, 96:108-114.
Paxinos G., Watson C. The rat brain in stereotaxic coordinates 2004, Elsevier Academic Press, NY.
Rayen I., van den Hove D.L., Prickaerts J., Steinbusch H.W., Pawluski J.L. Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence. PLoS ONE 2011, 6:e24003.
Romeo R.D. Pubertal maturation and programming of hypothalamic-pituitary-adrenal reactivity. Front Neuroendocrinol 2010, 31:232-240.
Romeo R.D., McEwen B.S. Stress and the adolescent brain. Ann N Y Acad Sci 2006, 1094:202-214.
Romijn H.J., Hofman M.A., Gramsbergen A. At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby?. Early Hum Dev 1991, 26:61-67.
Smith J.W., Seckl J.R., Evans A.T., Costall B., Smythe J.W. Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats. Psychoneuroendocrinology 2004, 29:227-244.
Tetel M.J., Auger A.P., Charlier T.D. Who's in charge? Nuclear receptor coactivator and corepressor function in brain and behavior. Front Neuroendocrinol 2009, 30:328-342.
Trousson A., Grenier J., Fonte C., Massaad-Massade L., Schumacher M., Massaad C. Recruitment of the p160 coactivators by the glucocorticoid receptor: dependence on the promoter context and cell type but not hypoxic conditions. J Steroid Biochem Mol Biol 2007, 104:305-311.
Uys J.D., Muller C.J., Marais L., Harvey B.H., Stein D.J., Daniels W.M. Early life trauma decreases glucocorticoid receptors in rat dentate gyrus upon adult re-stress: reversal by escitalopram. Neuroscience 2006, 137:619-625.
Van den Bergh B.R., Van Calster B., Smits T., Van Huffel S., Lagae L. Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence. a prospective study on the fetal origins of depressed mood. Neuropsychopharmacology 2008, 33:536-545.
Van den Hove D.L., Blanco C.E., Aendekerk B., Desbonnet L., Bruschettini M., Steinbusch H.P., Prickaerts J., Steinbusch H.W. Prenatal restraint stress and long-term affective consequences. Dev Neurosci 2005, 27:313-320.
Ververs T., Kaasenbrood H., Visser G., Schobben F., de Jong-van den L., BergEgberts T. Prevalence and patterns of antidepressant drug use during pregnancy. Eur J Clin Pharmacol 2006, 62:863-870.
Viau V. Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes. J Neuroendocrinol 2002, 14:506-513.
Viau V., Meaney M.J. Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat. Endocrinology 1991, 129:2503-2511.
Ward I.L., Weisz J. Differential effects of maternal stress on circulating levels of corticosterone, progesterone, and testosterone in male and female rat fetuses and their mothers. Endocrinology 1984, 114:1635-1644.
Weinstock M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 2008, 32:1073-1086.
Xu J., Kirigiti M.A., Grove K.L., Smith M.S. Regulation of food intake and gonadotropin-releasing hormone/luteinizing hormone during lactation: role of insulin and leptin. Endocrinology 2009, 150:4231-4240.
Yau J.L., Hibberd C., Noble J., Seckl J.R. The effect of chronic fluoxetine treatment on brain corticosteroid receptor mRNA expression and spatial memory in young and aged rats. Brain Res Mol Brain Res 2002, 106:117-123.
Yore M.A., Im D., Webb L.K., Zhao Y., Chadwick J.G., Molenda-Figueira H.A., Haidacher S.J., Denner L., Tetel M.J. Steroid receptor coactivator-2 expression in brain and physical associations with steroid receptors. Neuroscience 2010, 169:1017-1028.