Depression is a prevalent condition affecting up to 20% of pregnant women. Hence, more than 10% are prescribed antidepressant drugs, mainly serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs). We hypothesize that antidepressants disturb serotonin homeostasis in the fetoplacental unit by inhibiting serotonin transporter (SERT) and organic cation transporter 3 (OCT3) in the maternal- and fetal-facing placental membranes, respectively. Paroxetine, citalopram, fluoxetine, fluvoxamine, sertraline, and venlafaxine were tested in situ (rat term placenta perfusion) and ex vivo (uptake studies in membrane vesicles isolated from healthy human term placenta). All tested antidepressants significantly inhibited SERT- and OCT3-mediated serotonin uptake in a dose-dependent manner. Calculated half-maximal inhibitory concentrations (IC50) were in the range of therapeutic plasma concentrations. Using in vitro and in situ models, we further showed that the placental efflux transporters did not compromise mother-to-fetus transport of antidepressants. Collectively, we suggest that antidepressants have the potential to affect serotonin levels in the placenta or fetus when administered at therapeutic doses. Interestingly, the effect of antidepressants on serotonin homeostasis in rat placenta was sex dependent. As accurate fetal programming requires optimal serotonin levels in the fetoplacental unit throughout gestation, inhibition of SERT-/OCT3-mediated serotonin uptake may help explain the poor outcomes of antidepressant use in pregnancy.

Department of Pharmacology and Toxicology Faculty of Pharmacy in Hradec Kralove Charles University Akademika Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

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Pawluski J.L., Lonstein J.S., Fleming A.S. The Neurobiology of Postpartum Anxiety and Depression. Trends Neurosci. 2017;40:106–120. doi: 10.1016/j.tins.2016.11.009. PubMed DOI

Hagberg K.W., Robijn A.L., Jick S. Maternal depression and antidepressant use during pregnancy and the risk of autism spectrum disorder in offspring. Clin. Epidemiol. 2018;10:1599–1612. doi: 10.2147/CLEP.S180618. PubMed DOI PMC

Cooper W.O., Willy M.E., Pont S.J., Ray W.A. Increasing use of antidepressants in pregnancy. Am. J. Obstet. Gynecol. 2007;196:544.e1-5. doi: 10.1016/j.ajog.2007.01.033. PubMed DOI

Charlton R.A., Jordan S., Pierini A., Garne E., Neville A.J., Hansen A.V., Gini R., Thayer D., Tingay K., Puccini A., et al. Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: A population-based study in six European regions. Bjog. 2015;122:1010–1020. doi: 10.1111/1471-0528.13143. PubMed DOI

Oberlander T.F., Gingrich J.A., Ansorge M.S. Sustained neurobehavioral effects of exposure to SSRI antidepressants during development: Molecular to clinical evidence. Clin. Pharmacol. Ther. 2009;86:672–677. doi: 10.1038/clpt.2009.201. PubMed DOI PMC

Videman M., Tokariev A., Saikkonen H., Stjerna S., Heiskala H., Mantere O., Vanhatalo S. Newborn Brain Function Is Affected by Fetal Exposure to Maternal Serotonin Reuptake Inhibitors. Cereb. Cortex. 2017;27:3208–3216. doi: 10.1093/cercor/bhw153. PubMed DOI

Bonnin A., Levitt P. Placental Source for 5-HT that Tunes Fetal Brain Development. Neuropsychopharmacology. 2012;37:299–300. doi: 10.1038/npp.2011.194. PubMed DOI PMC

Maroteaux L., Kilic F. Frontiers of Serotonin Beyond the Brain. Pharmacol. Res. 2019;140:1–6. doi: 10.1016/j.phrs.2018.10.022. PubMed DOI PMC

Staud F., Karahoda R. Trophoblast: The central unit of fetal growth, protection and programming. Int. J. Biochem. Cell Biol. 2018;105:35–40. doi: 10.1016/j.biocel.2018.09.016. PubMed DOI

Malm H., Brown A.S., Gissler M., Gyllenberg D., Hinkka-Yli-Salomäki S., McKeague I.W., Weissman M., Wickramaratne P., Artama M., Gingrich J.A., et al. Gestational Exposure to Selective Serotonin Reuptake Inhibitors and Offspring Psychiatric Disorders: A National Register-Based Study. J. Am. Acad. Child Adolesc. Psychiatry. 2016;55:359–366. doi: 10.1016/j.jaac.2016.02.013. PubMed DOI PMC

Liu X., Agerbo E., Ingstrup K.G., Musliner K., Meltzer-Brody S., Bergink V., Munk-Olsen T. Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study. BMJ. 2017;358:j3668. doi: 10.1136/bmj.j3668. PubMed DOI PMC

Viktorin A., Uher R., Reichenberg A., Levine S.Z., Sandin S. Autism risk following antidepressant medication during pregnancy. Psychol. Med. 2017;47:2787–2796. doi: 10.1017/S0033291717001301. PubMed DOI PMC

Morales D.R., Slattery J., Evans S., Kurz X. Antidepressant use during pregnancy and risk of autism spectrum disorder and attention deficit hyperactivity disorder: Systematic review of observational studies and methodological considerations. BMC Med. 2018;16:6. doi: 10.1186/s12916-017-0993-3. PubMed DOI PMC

Boukhris T., Sheehy O., Mottron L., Berard A. Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children. JAMA Pediatr. 2016;170:117–124. doi: 10.1001/jamapediatrics.2015.3356. PubMed DOI

Gidaya N.B., Lee B.K., Burstyn I., Yudell M., Mortensen E.L., Newschaffer C.J. In utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder. J. Autism Dev. Disord. 2014;44:2558–2567. doi: 10.1007/s10803-014-2128-4. PubMed DOI

Sato K. Placenta-derived hypo-serotonin situations in the developing forebrain cause autism. Med. Hypotheses. 2013;80:368–372. doi: 10.1016/j.mehy.2013.01.002. PubMed DOI

Yang C.J., Tan H.P., Du Y.J. The developmental disruptions of serotonin signaling may involved in autism during early brain development. Neuroscience. 2014;267:1–10. doi: 10.1016/j.neuroscience.2014.02.021. PubMed DOI

Pawluski J.L., Rayen I., Niessen N.A., Kristensen S., van Donkelaar E.L., Balthazart J., Steinbusch H.W., Charlier T.D. Developmental fluoxetine exposure differentially alters central and peripheral measures of the HPA system in adolescent male and female offspring. Neuroscience. 2012;220:131–141. doi: 10.1016/j.neuroscience.2012.06.034. PubMed DOI

Palmsten K., Huybrechts K.F., Michels K.B., Williams P.L., Mogun H., Setoguchi S., Hernández-Díaz S. Antidepressant use and risk for preeclampsia. Epidemiology. 2013;24:682–691. doi: 10.1097/EDE.0b013e31829e0aaa. PubMed DOI PMC

Bernard N., Forest J.-C., Tarabulsy G.M., Bujold E., Bouvier D., Giguère Y. Use of antidepressants and anxiolytics in early pregnancy and the risk of preeclampsia and gestational hypertension: A prospective study. BMC Pregnancy Childbirth. 2019;19:146. doi: 10.1186/s12884-019-2285-8. PubMed DOI PMC

Marchocki Z., Russell N.E., Donoghue K.O. Selective serotonin reuptake inhibitors and pregnancy: A review of maternal, fetal and neonatal risks and benefits. Obstet. Med. 2013;6:155–158. doi: 10.1177/1753495X13495194. PubMed DOI PMC

Fornaro E., Li D., Pan J., Belik J. Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat. Am. J. Respir. Crit. Care Med. 2007;176:1035–1040. doi: 10.1164/rccm.200701-163OC. PubMed DOI

Harrington R.A., Lee L.C., Crum R.M., Zimmerman A.W., Hertz-Picciotto I. Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics. 2014;133:e1241–e1248. doi: 10.1542/peds.2013-3406. PubMed DOI PMC

Bérard A., Zhao J.P., Sheehy O. Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: An updated analysis of the Quebec Pregnancy Cohort. BMJ Open. 2017;7:e013372. doi: 10.1136/bmjopen-2016-013372. PubMed DOI PMC

Diav-Citrin O., Shechtman S., Weinbaum D., Wajnberg R., Avgil M., Di Gianantonio E., Clementi M., Weber-Schoendorfer C., Schaefer C., Ornoy A. Paroxetine and fluoxetine in pregnancy: A prospective, multicentre, controlled, observational study. Br. J. Clin. Pharm. 2008;66:695–705. doi: 10.1111/j.1365-2125.2008.03261.x. PubMed DOI PMC

Gao S.-Y., Wu Q.-J., Sun C., Zhang T.-N., Shen Z.-Q., Liu C.-X., Gong T.-T., Xu X., Ji C., Huang D.-H., et al. Selective serotonin reuptake inhibitor use during early pregnancy and congenital malformations: A systematic review and meta-analysis of cohort studies of more than 9 million births. BMC Med. 2018;16:205. doi: 10.1186/s12916-018-1193-5. PubMed DOI PMC

Zhang T.N., Gao S.Y., Shen Z.Q., Li D., Liu C.X., Lv H.C., Zhang Y., Gong T.T., Xu X., Ji C., et al. Use of selective serotonin-reuptake inhibitors in the first trimester and risk of cardiovascular-related malformations: A meta-analysis of cohort studies. Sci. Rep. 2017;7:43085. doi: 10.1038/srep43085. PubMed DOI PMC

Nordeng H., Lindemann R., Perminov K.V., Reikvam A. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr. 2001;90:288–291. doi: 10.1080/080352501300067596. PubMed DOI

Jensen H.M., Grøn R., Lidegaard Ø., Pedersen L.H., Andersen P.K., Kessing L.V. Maternal depression, antidepressant use in pregnancy and Apgar scores in infants. Br. J. Psychiatry. 2013;202:347–351. doi: 10.1192/bjp.bp.112.115931. PubMed DOI

Simon G.E., Cunningham M.L., Davis R.L. Outcomes of prenatal antidepressant exposure. Am. J. Psychiatry. 2002;159:2055–2061. doi: 10.1176/appi.ajp.159.12.2055. PubMed DOI

Zhao X., Liu Q., Cao S., Pang J., Zhang H., Feng T., Deng Y., Yao J., Li H. A meta-analysis of selective serotonin reuptake inhibitors (SSRIs) use during prenatal depression and risk of low birth weight and small for gestational age. J. Affect Disord. 2018;241:563–570. doi: 10.1016/j.jad.2018.08.061. PubMed DOI

Karahoda R., Horackova H., Kastner P., Matthios A., Cerveny L., Kucera R., Kacerovsky M., Duintjer Tebbens J., Bonnin A., Abad C., et al. Serotonin homeostasis in the materno-foetal interface at term: Role of transporters (SERT/SLC6A4 and OCT3/SLC22A3) and monoamine oxidase A (MAO-A) in uptake and degradation of serotonin by human and rat term placenta. Acta Physiol. 2020;229:e13478. doi: 10.1111/apha.13478. PubMed DOI PMC

Karahoda R., Abad C., Horackova H., Kastner P., Zaugg J., Cerveny L., Kucera R., Albrecht C., Staud F. Dynamics of Tryptophan Metabolic Pathways in Human Placenta and Placental-Derived Cells: Effect of Gestation Age and Trophoblast Differentiation. Front. Cell Dev. Biol. 2020;8:574034. doi: 10.3389/fcell.2020.574034. PubMed DOI PMC

Abad C., Karahoda R., Kastner P., Portillo R., Horackova H., Kucera R., Nachtigal P., Staud F. Profiling of Tryptophan Metabolic Pathways in the Rat Fetoplacental Unit During Gestation. Int. J. Mol. Sci. 2020;21:7578. doi: 10.3390/ijms21207578. PubMed DOI PMC

Bonnin A., Goeden N., Chen K., Wilson M.L., King J., Shih J.C., Blakely R.D., Deneris E.S., Levitt P. A transient placental source of serotonin for the fetal forebrain. Nature. 2011;472:347–350. doi: 10.1038/nature09972. PubMed DOI PMC

Sano M., Ferchaud-Roucher V., Kaeffer B., Poupeau G., Castellano B., Darmaun D. Maternal and fetal tryptophan metabolism in gestating rats: Effects of intrauterine growth restriction. Amino Acids. 2016;48:281–290. doi: 10.1007/s00726-015-2072-4. PubMed DOI

Arevalo R., Afonso D., Castro R., Rodriguez M. Fetal brain serotonin synthesis and catabolism is under control by mother intake of tryptophan. Life Sci. 1991;49:53–66. doi: 10.1016/0024-3205(91)90579-Z. PubMed DOI

Zhu H.-J., Appel D.I., Gründemann D., Richelson E., Markowitz J.S. Evaluation of organic cation transporter 3 (SLC22A3) inhibition as a potential mechanism of antidepressant action. Pharmacol. Res. 2012;65:491–496. doi: 10.1016/j.phrs.2012.01.008. PubMed DOI

Staud F., Cerveny L., Ceckova M. Pharmacotherapy in pregnancy; effect of ABC and SLC transporters on drug transport across the placenta and fetal drug exposure. J. Drug Target. 2012;20:736–763. doi: 10.3109/1061186X.2012.716847. PubMed DOI

Illsley N.P., Wang Z.Q., Gray A., Sellers M.C., Jacobs M.M. Simultaneous preparation of paired, syncytial, microvillous and basal membranes from human placenta. Biochim. Biophys. Acta. 1990;1029:218–226. doi: 10.1016/0005-2736(90)90157-J. PubMed DOI

Staud F., Vackova Z., Pospechova K., Pavek P., Ceckova M., Libra A., Cygalova L., Nachtigal P., Fendrich Z. Expression and transport activity of breast cancer resistance protein (Bcrp/Abcg2) in dually perfused rat placenta and HRP-1 cell line. J. Pharmacol. Exp. Ther. 2006;319:53–62. doi: 10.1124/jpet.106.105023. PubMed DOI

Karbanova S., Cerveny L., Jiraskova L., Karahoda R., Ceckova M., Ptackova Z., Staud F. Transport of ribavirin across the rat and human placental barrier: Roles of nucleoside and ATP-binding cassette drug efflux transporters. Biochem. Pharmacol. 2019;163:60–70. doi: 10.1016/j.bcp.2019.01.024. PubMed DOI

Laemmli U.K. Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4. Nature. 1970;227:680–685. doi: 10.1038/227680a0. PubMed DOI

Feix J.B., Bachowski G.J., Girotti A.W. Photodynamic action of merocyanine 540 on erythrocyte membranes: Structural perturbation of lipid and protein constituents. Biochim. Biophys. Acta. 1991;1075:28–35. doi: 10.1016/0304-4165(91)90070-W. PubMed DOI

Neumanova Z., Cerveny L., Ceckova M., Staud F. Interactions of tenofovir and tenofovir disoproxil fumarate with drug efflux transporters ABCB1, ABCG2, and ABCC2; role in transport across the placenta. Aids. 2014;28:9–17. doi: 10.1097/QAD.0000000000000112. PubMed DOI

Neumanova Z., Cerveny L., Greenwood S.L., Ceckova M., Staud F. Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir. Reprod. Toxicol. 2015;57:176–182. doi: 10.1016/j.reprotox.2015.07.070. PubMed DOI

Martinec O., Huliciak M., Staud F., Cecka F., Vokral I., Cerveny L. Anti-HIV and Anti-Hepatitis C Virus Drugs Inhibit P-Glycoprotein Efflux Activity in Caco-2 Cells and Precision-Cut Rat and Human Intestinal Slices. Antimicrob. Agents Chemother. 2019;63:e00910-00919. doi: 10.1128/AAC.00910-19. PubMed DOI PMC

Eap C.B., Bouchoux G., Amey M., Cochard N., Savary L., Baumann P. Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline, and their metabolites by gas chromatography-mass spectrometry. J. Chromatogr. Sci. 1998;36:365–371. doi: 10.1093/chromsci/36.7.365. PubMed DOI

Reis M., Aamo T., Spigset O., Ahlner J. Serum concentrations of antidepressant drugs in a naturalistic setting: Compilation based on a large therapeutic drug monitoring database. Ther. Drug Monit. 2009;31:42–56. doi: 10.1097/FTD.0b013e31819114ea. PubMed DOI

Baumann P. Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin. Pharm. 1996;31:444–469. doi: 10.2165/00003088-199631060-00004. PubMed DOI

Ewing G., Tatarchuk Y., Appleby D., Schwartz N., Kim D. Placental transfer of antidepressant medications: Implications for postnatal adaptation syndrome. Clin. Pharmacokinet. 2015;54:359–370. doi: 10.1007/s40262-014-0233-3. PubMed DOI PMC

Chiarello D.I., Abad C., Rojas D., Toledo F., Vázquez C.M., Mate A., Sobrevia L., Marín R. Oxidative stress: Normal pregnancy versus preeclampsia. Biochim. Biophys. Acta Mol. Basis Dis. 2020;1866:165354. doi: 10.1016/j.bbadis.2018.12.005. PubMed DOI

Dubovicky M., Belovicova K., Csatlosova K., Bogi E. Risks of using SSRI / SNRI antidepressants during pregnancy and lactation. Interdiscip. Toxicol. 2017;10:30–34. doi: 10.1515/intox-2017-0004. PubMed DOI PMC

Corti S., Pileri P., Mazzocco M.I., Mandò C., Moscatiello A.F., Cattaneo D., Cheli S., Baldelli S., Pogliani L., Clementi E., et al. Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure. Front. Pediatrics. 2019;7:309. doi: 10.3389/fped.2019.00309. PubMed DOI PMC

Ng Q.X., Venkatanarayanan N., Ho C.Y.X., Sim W.S., Lim D.Y., Yeo W.S. Selective Serotonin Reuptake Inhibitors and Persistent Pulmonary Hypertension of the Newborn: An Update Meta-Analysis. J. Womens Health. 2019;28:331–338. doi: 10.1089/jwh.2018.7319. PubMed DOI

Man K.K.C., Tong H.H.Y., Wong L.Y.L., Chan E.W., Simonoff E., Wong I.C.K. Exposure to selective serotonin reuptake inhibitors during pregnancy and risk of autism spectrum disorder in children: A systematic review and meta-analysis of observational studies. Neurosci. Biobehav. Rev. 2015;49:82–89. doi: 10.1016/j.neubiorev.2014.11.020. PubMed DOI

Kobayashi T., Matsuyama T., Takeuchi M., Ito S. Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis. Reprod. Toxicol. 2016;65:170–178. doi: 10.1016/j.reprotox.2016.07.016. PubMed DOI

Hranilovic D., Blazevic S. Hyperserotonemia in Autism: 5HT-Regulating Proteins. In: Patel V.B., Preedy V.R., Martin C.R., editors. Comprehensive Guide to Autism. Springer; New York, NY, USA: 2014. pp. 717–739. DOI

Ramamoorthy S., Bauman A.L., Moore K.R., Han H., Yang-Feng T., Chang A.S., Ganapathy V., Blakely R.D. Antidepressant- and cocaine-sensitive human serotonin transporter: Molecular cloning, expression, and chromosomal localization. Proc. Natl. Acad. Sci. USA. 1993;90:2542–2546. doi: 10.1073/pnas.90.6.2542. PubMed DOI PMC

Rosenfeld C.S. The placenta-brain-axis. J. Neurosci. Res. 2021;99:271–283. doi: 10.1002/jnr.24603. PubMed DOI PMC

Balkovetz D.F., Tiruppathi C., Leibach F.H., Mahesh V.B., Ganapathy V. Evidence for an imipramine-sensitive serotonin transporter in human placental brush-border membranes. J. Biol. Chem. 1989;264:2195–2198. doi: 10.1016/S0021-9258(18)94161-X. PubMed DOI

Fraser-Spears R., Krause-Heuer A.M., Basiouny M., Mayer F.P., Manishimwe R., Wyatt N.A., Dobrowolski J.C., Roberts M.P., Greguric I., Kumar N., et al. Comparative analysis of novel decynium-22 analogs to inhibit transport by the low-affinity, high-capacity monoamine transporters, organic cation transporters 2 and 3, and plasma membrane monoamine transporter. Eur. J. Pharmacol. 2019;842:351–364. doi: 10.1016/j.ejphar.2018.10.028. PubMed DOI PMC

Jansson T., Illsley N.P. Osmotic water permeabilities of human placental microvillous and basal membranes. J. Membr. Biol. 1993;132:147–155. doi: 10.1007/BF00239004. PubMed DOI

Dickinson H., Moss T.J., Gatford K.L., Moritz K.M., Akison L., Fullston T., Hryciw D.H., Maloney C.A., Morris M.J., Wooldridge A.L., et al. A review of fundamental principles for animal models of DOHaD research: An Australian perspective. J. Dev. Orig. Health Dis. 2016;7:449–472. doi: 10.1017/S2040174416000477. PubMed DOI

Gobinath A.R., Workman J.L., Chow C., Lieblich S.E., Galea L.A.M. Sex-dependent effects of maternal corticosterone and SSRI treatment on hippocampal neurogenesis across development. Biol. Sex Differ. 2017;8:20. doi: 10.1186/s13293-017-0142-x. PubMed DOI PMC

Gobinath A.R., Workman J.L., Chow C., Lieblich S.E., Galea L.A. Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis. Neuropharmacology. 2016;101:165–178. doi: 10.1016/j.neuropharm.2015.09.001. PubMed DOI

Audus K.L. Controlling drug delivery across the placenta. Eur. J. Pharm. Sci. 1999;8:161–165. doi: 10.1016/S0928-0987(99)00031-7. PubMed DOI

Uhr M., Tontsch A., Namendorf C., Ripke S., Lucae S., Ising M., Dose T., Ebinger M., Rosenhagen M., Kohli M., et al. Polymorphisms in the Drug Transporter Gene ABCB1 Predict Antidepressant Treatment Response in Depression. Neuron. 2008;57:203–209. doi: 10.1016/j.neuron.2007.11.017. PubMed DOI

Feng B., Mills J.B., Davidson R.E., Mireles R.J., Janiszewski J.S., Troutman M.D., de Morais S.M. In vitro P-glycoprotein assays to predict the in vivo interactions of P-glycoprotein with drugs in the central nervous system. Drug Metab. Dispos. 2008;36:268–275. doi: 10.1124/dmd.107.017434. PubMed DOI

Wichman C.L., Stern T.A. Diagnosing and Treating Depression During Pregnancy. Prim. Care Companion CNS Disord. 2015;17:10.4088/PCC.4015f01776. doi: 10.4088/PCC.15f01776. PubMed DOI PMC

Thormahlen G.M. Paroxetine use during pregnancy: Is it safe? Ann. Pharm. 2006;40:1834–1837. doi: 10.1345/aph.1H116. PubMed DOI

Horton R.E. Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: Uncovering novel targets to treat depression. J. Neurosci. 2013;33:10534–10543. doi: 10.1523/JNEUROSCI.5687-11.2013. PubMed DOI PMC

Margraf A. Maturation of Platelet Function During Murine Fetal Development In Vivo. Arterioscler. Thromb. Vasc. Biol. 2017;37:1076–1086. doi: 10.1161/ATVBAHA.116.308464. PubMed DOI

Mercado C.P., Kilic F. Molecular mechanisms of SERT in platelets: Regulation of plasma serotonin levels. Mol. Interv. 2010;10:231–241. doi: 10.1124/mi.10.4.6. PubMed DOI PMC

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