Developmental and Behavioral Consequences of Prenatal FluoxetineBairy K.L.a · Madhyastha S.c · Ashok K.P.d · Bairy I.b · Malini S.a
Departments of aPharmacology and bMicrobiology, Kasturba Medical College, Manipal, and Departments of cAnatomy and dPharmacology, Kasturba Medical College, Mangalore, India
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Background: Fluoxetine, a selective serotonin reuptake inhibitor, is the most commonly prescribed antidepressant drug for pregnant women. Studies regarding the teratogenic effect of fluoxetine on human and animal models are mainly concerned with structural malformation (congenital anomalies). Aim: Hence, the present study was planned to evaluate the postnatal behavioral effects of fluoxetine on albino rats. Methods: Three groups of female rats received either distilled water or doses of fluoxetine 8 and 12 mg/kg orally from the 6th to the 20th day of pregnancy. Weaning of the pups was done on the 21st day followed by a battery of behavioral tests to assess for any behavioral effect. The tests included negative geotaxis, open field exploration, rota-rod test, elevated plus maze and passive avoidance test. Results: In the present study there was no change in the gestational length of pregnancy, no premature birth or miscarriage during pregnancy. A high dose of in utero fluoxetine resulted in a decrease in birth weight of the offspring and also reduced weight gain during the preweaning period. No major congenital abnormalities were observed in the offspring exposed to fluoxetine. Prenatal fluoxetine exposure at high dose caused an initial transient delay in motor development and this poor motor activity was transient and not permanent. However, prenatal exposure to fluoxetine at a higher dose showed a favorable effect on learning and memory in water maze and passive avoidance tests. Conclusions: From the present study, it may be concluded that prenatal fluoxetine causes a transient delay in motor development but does not adversely affect the postnatal behavioral consequences.
© 2007 S. Karger AG, Basel
- Callahan BT, Yuan J, Ricaurte GA: Fluoxetine increases the anorectic and long-term dopamine-depleting effects of phentermine. Synapse 2000;38:471–476.
Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL: Birth outcomes in pregnant women taking fluoxetine. N Eng J Med 1996;35:1010–1015.
- Vorhees C, Acuff-Smith K, Schilling M, Fisher J, Moran M, Buelke-Sam JA: Developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. Fundam Appl Toxicol 1994;23:194–205.
- Stewart C, Scalzo F, Valentine J, Holson R, Ali S, Slikker W: Gestational exposure to cocaine or pharmacologically related compounds: effects on behavior and striatal dopamine receptors. Life Sci 1998;63:2015– 2022.
- Da-Silva VA, Altenburg SP, Malheiros LR, Thomaz TG, Lindsey CJ: Postnatal development of rats exposed to fluoxetine or venlafaxine during the third week of pregnancy. Braz J Med Biol Res 1999;32:93–98.
- Addis A, Koren G: Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies. Psychol Med 2000;30:89–94.
- Janna L, Morrison AD, Wayne Riggs B, Dan W, Rurak C: Fluoxetine during pregnancy: impact on fetal development. Reprod Fert Dev 2005;17:641–650.
- Nulman I, Korean G: The safety of fluoxetine during pregnancy and lactation. Teratology 1996;53:304–308.
- Goulart EC, Pereira CAT, Garcia RC, Giacomelli MBO, Rodrigues ALS: Effects of lead and/or zinc exposure during the second stage of rapid postnatal brain growth on delta-aminolevulinate dehydratase and negative geotaxis of suckling rats. Braz J Med Biol Res 2001;34:785–790.
Tobach E: Manipulation effects, open field experience and digestive transit time in Wistar male and female rats. Psychol Rep 1996;19:375–378.
Bures J, Buresova D: Learning and memory; in Bures J, Buresova, Houstan JP (eds): Techniques and Basic Experiments for the Study of Brain and Behavior. New York, Elsevier, 1983, pp 148–152.
- Hamm RJ, Pike BR, O’Dell DM, Lyeth BG, Jenkins LW: The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma 1994;11:187–196.
- Morris RGM: Spatial localization does not depend on the presence of local cues. Learn Motiv 1981;12:239–260.
- Brown RW, Kraemer PJ: Ontogenetic differences in retention of spatial learning tested with Morris water maze. Dev Psychobiol 1997;30:329–341.
- Varty GB, Morgan CA, Cohen-Williams ME, Coffin VL, Carey GJ: The Gerbil Elevated Plus-Maze I: behavioral characterization and pharmacological validation. Neuropsychopharmacology 2002;27:357–370.
- Liang KC, Tsui KY, Tyan YM, Chiang TC: Buspirone impaired acquisition and retention in avoidance tasks: involvement of the hippocampus. Chin J Physiol 1998;41:33–44.
Azmita EC, Whitaker-Azmita PM: Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system. J Clin Psychiatry 1991;52:4–14.
Jacob EL, Formal CA: Activity of brain serotonergic neurons in the behaving animal. Pharmacol Rev 1991;43:563–578.
Gross-Isseroff R, Salama D, Iisraeli M, Biegon A: Autoradiography analysis of age-dependent changes in serotonin 5-HT2 receptor of the human brain postmortem.Brain Res 1990;21:381–399.
- Vannier B, Saillenfait AM: Methodological proposal in behavioral teratogenicity testing: assessment of propoxyphene, chlorpromazine, and vitamin A as positive controls. Teratology 1988;37:185–199.
Vedernikov Y, Bolanos S, Bytautiene E: Effects of fluoxetine on contractile activity of pregnant rat uterine rings. Am J Obstet Gynecol 2002;182:269–279.
- Tuomsti J, Mannisto P: Neurotransmitter regulation of anterior pituitary hormones. Pharmacol Rev 1985;37:249–332.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.