Author
Department of Biology , Collage of Education for Pure Science , Mosul University , Mosul ,Iraq
,
Document Type : Research Paper
Abstract
The present study was designed to identify the histopathological effect of fluoxetine (fluoxetine hydrochloride) on the pregnant mice brain and their fetuses as well as recording weight changes at doses of 60 and 80 mg/kg of body weight which were administrated to the pregnant mice from the 7th up to the 18th day of pregnancy and once a day. The results showed histopathological lesions in the adult pregnant mice brain at the dose of 60 mg/kg. induced massive necrotic area of neurons in the cerebral cortex, necrosis of the molecular layer cells while the dose of 80 mg/kg the changes include vasogenic edema in the sub cortical area, severe degeneration and necrosis of the cortex. The lesions in cerebellum were more severe than recorded in the cerebrum. The results also showed the presence of many lesions in the fetus brain at the dose 60 mg/kg and they were degeneration, necrosis of many neurons in the cerebrum while at the dose of 80 mg/kg. There were increase of degeneration and necrosis in the cortical area of fetus brain. In conclusion, the use of fluoxetine in pregnant mice caused decrease in body weight and Histopathological changes in the brain of both of the mothers and their embryos, thus the use of antidepressant by pregnant woman can be harmful for the mothers and the fetus.
- Aboni S, Dijk R, Poggini S, Milior G, Perrotta M, Drenth T, Brunello N, Wolfer DP, Limatila C, Amrein I, Circulli F, Maggi L, Branchi I. Fluoxetine DOI: 10.1038/MP. 2015.142effects on molecular, cellular and behavioural endophenotypes of depression are driven by living environments. Mole Psychol. 2017;22:552-561.
- Andrade S, Raebel M, Brown J, Jane K, Livingstone, J, Smith , Willy D, E, Staffa A, Platt R. Use of antidepressant medication during pregnancy: a multisite study. Am J Obstet Gynecol. 2008;e1991-e195. DOI: 10.1016/j. a jog. 2007.07.036
- Baudry A, Mouillet S, Schneider B, Launay M, Kellermann O. MiR-16 target the serotonin transporter: A new facet for adaptive response to antidepressant. Sci. 2010;329(5998):1537-154. DOI: 10.1126/science.1193692
- Fournier,J.C.; Derubeis,J.R.;Hollon,S.D.; Dimidjiani , S.; Amsterdam, J.D.; Shelton , R. C.; Fawcett,j. Antidepressant drug effects and depression sever : A Patient-Level Meta-Analysisity . J Am Med Associ. 2010;303(1):47-53.
- Cipriani A, Brambilla P, Furukawa T, Geddes J, Gregis M, Hotope M, Malvini L, Barbui C. Fluoxetine versus other types of pharmacotherapy for depression database. Syst Rev. 2005;9(2):81-85. DOI: 10.1002/14651858.CD004185.pub2
- Yohn N, Shifman A, Diethorn L, Bokka L, Ashamalla A, Samules A. Fluoxetine effects on behavior and adult hippocampal neurogenesis in female C57BL / 6J mice across the estrous cycle. Rixiv. 2018;4:1-25. doi: https://doi.org/10.1101/368449
- Zinga D, Phillips D, Born L. Postpartum depression: We know the risks, can it be prevented? Rev Bras Psiquiater. 2005;27(2):56-64. http://dx.doi.org/10.1590/S1516-44462005000600005
- Libosa F, Oliveira E, Costa C, Venancio J, Moreira G. Behavioral evaluation of male and female mice pups exposed to fluoxetine during pregnancy and lactation. Pharmacol. 2007;80:49-56. DOI: 10.1159/000103097
- Olivier A, Valls A, VanHeesch F, Afrasiab A, Roeloes M, Jonkers M, Peeters J, Korte H, Dederen P, Kilian J, Martens J, Schubert D, Homberg R. Fluoxetine administration to pregnant rats increases anxiety- related behavior in the offspring. Psychopharmacol. 2011;11:217-414.
- Marcus M, Flynn A. Depression, antidepressant medication and functioning outcomes among pregnant women. Inter J Gynaecol Obstet. 2008;100(3):248-251. DOI: 10.1016/j.ijgo.2007.09.016
- Czeizel E, Puho H, Acs N, Banhidy F. Use of specified critical periods of different congenital abnormalities instead of the first trimester concept. Birth Defects Res Clin Mol Teratol. 2008;82(3):139-146. DOI: 10.1002/bdra.20431
- Goldstein J. Outcomes of fluoxetine exposed in pregnancy. Am J Hum Genet. 1990;47:136.
- Saker H, Abbas A, Elsamanoudy A, Ghoneim F. Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mild stress-induced depression. J Physio Pharma. 2015;66:515-527. PMID: 26348076
- Abdul-Salam E. The effect of antidepressant drugs on thioacetamide- induced oxidative stress. Euro Rev Med Pharmacol Sci. 2013;17:735-744. PMID: 23609356
- Ramos E, St-Andre M, Rey E, Oravichi D, Berard A. Duration of antidepressant use during pregnancy and risk of major congenital malformations. Br J Psychiatr. 2008;192(5):344-350. doi: 10.1192/bjp.bp.107.042523.
- Ali O, Sharf A, El menshawy M, Barkry A. Fluoxetine HCL induced intrauterine fetal growth retardation and skeletal malformation in pregnant mice. Egy J Hosp Med. 2002;6:63-79. DOI:10.12816/ejhm.2002.18857
- Ali O, El- Nahass E, Diamond O, Desouki G. Embryo toxic effect diabetes mellitus. Al-Azhar Med J. 1989;17(4):421-228. DOI: 10.1056/NEJM199309303291401
- Wang T, Bymas P, Engleman A. Prozac (fluoxetine, Lilly 110140), the first selective serotonin uptake inhibitor and antidepressant drug: Twenty years since its first publication. Life Sci. 1995;57(5):411-441. DOI: 10.1016/0024-3205(95)00209-o
- Swerts S, Costa D, Estenes A, Borato S, Swerts O. Effects of fluoxetine and imipramine in rat fetuses treated during a critical gestational period: A macro and microscopic study. Rev Bras Psiquiatr. 2010;32(2):1-10. http://dx.doi.org/10.1590/S1516-44462009005000015
- A-Hajj A. Optical laboratory preparation. 1st ed. Amman: Dar Al-Massera; 2010. 40-44 p.
- Bendale A, Adams R, Hoffman P, Gries L, Morton M. Carcinogenicity studies of fluoxetine hydrochloride in rats and mice. Cancer Res. 1992;52(24):6931-5.
- Holick A, Lee C, Hen R, Dulawa C. Behavioral effects of chronic fluoxetine in Balb/C mice do not require adult hippocampus neurogenesis or the serotonin IA receptor. Neuropsychopharmacol. 2008;33:406-417.
- Ohira K, Miykawa T. Chronic treatment with fluoxetine for more than 6 weeks decreases neurogenesis in the subventricular zone of adult mice. Mol Brain. 2011;4:10. doi: 10.1186/1756-6606-4-10
- Rasul H, Mohamood S, Hamad H, Hassan H. Histological changes of the liver, kidney and brain in uninephrectomized male rats exposed to fluoxetine. ZIPAS. 2016;28(6):106-121.
- Marlatt, M. ; Lucassen ,P. ; Praag ,H. (2010). Comparison of neurogenic effects of fluoxetine, duloxetine and running in mice.Brain Res.1341:93-99. doi: 10.1016/j.brainres.2010.03.086
- Chen H, Panday N, Dwivedi Y. Hippocampal cell proliferation regulation by repeated stress and antidepressants. Neuroeport. 2006;17:863-867. DOI: 10.1097/01.wnr.0000221827.03222.70
- Kroeze Y, Peeters D, Boulle F, Avanden H, Bokhoven V, Zhou H, Homberg R. Long- term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus. Psychiatry. 2015;6(4):e779. doi: 10.1038/tp.2015.145.
- Cabrera- vera M, Battaglia G. Delayed decrease in brain 5- hydroxytryptamine 2A/ 2C receptor density and function in male rate progeny following prenatal fluoxetine. J Pharmacol Exp Ther. 1994;209:637-645.
- Pohland C, Koons R. Placental transfer and fetal distribution of fluoxetine in the rat. Toxicol Appl Pharmacol. 1989;98(2):198-205. DOI: 10.1016/0041-008x(89)90225-1
- Gutterigae C. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clinic Chem. 1995;41:1819-1828.
- Altemus M, Glowa R, Galliven E, Leong M, Murphy L. Effects of serotonergic agent on food restriction induced hyperactivity. Pharmacol Biochem Behav. 1996;53(1):123-131.
- Curzan G, Gibson L, Oluyomi O. Appetite suppression by commonly used drugs depends on 5-HT receptors but not on 5HT availability. Pharmacol Sci. 1997;18(1):21-25.
- Vorhess V, Acuff-Smith K D, Schilling A. A developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. Fundam App Toxicol. 1994;23(2):194-205.
- Ali M, Hakami A. Comparative studies on the effect of prozac drug and barely grains on the skeletal muscles of mice: Behavioral and histological studies. J Appl Pharm Sci. 2012;2(03):45-51.
- Eugenia P, Vari E, Maria D. Fluoxetine effect on gestation and fetal development. Acta Med Marisiensis. 2014;60(4):157-159. DOI: https://doi.org/10.2478/amma-2014-0034
- Dryden S, Frankish M, Wang Q, Pickavance L, Williams G. The serotonergic agent fluoxtine reduces neuropeptide Y levels and neuropeptide Y secretion in the hypothalamus of lean and obese rats. Neurosci. 1996;72(2):557-566.