NDLI: Low-dose paroxetine exposure causes lifetime declines in male mouse body weight, reproduction and competitive ability as measured by the novel organismal performance assay

Content Provider	PubMed Central
Author	Gaukler, Shannon M. Ruff, James S. Galland, Tessa Kandaris, Kirstie A. Underwood, Tristan K. Liu, Nicole M. Young, Elizabeth L. Morrison, Linda C. Yost, Garold S. Potts, Wayne K.
Copyright Year	2014
Abstract	Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is currently available on the market and is suspected of causing congenital malformations in babies born to mothers who take the drug during the first trimester of pregnancy. We utilized organismal performance assays (OPAs), a novel toxicity assessment method, to assess the safety of paroxetine during pregnancy in a rodent model. OPAs utilize genetically diverse wild mice (Mus musculus) to evaluate competitive performance between experimental and control animals as they compete amongst each other for limited resources in semi-natural enclosures. Performance measures included reproductive success, male competitive ability and survivorship. Paroxetine-exposed males weighed 13% less, had 44% fewer offspring, dominated 53% fewer territories and experienced a 2.5-fold increased trend in mortality, when compared with controls. Paroxetine-exposed females had 65% fewer offspring early in the study, but rebounded at later time points. In cages, paroxetine-exposed breeders took 2.3 times longer to produce their first litter and pups of both sexes experienced reduced weight when compared with controls. Low-dose paroxetine-induced health declines detected in this study were undetected in preclinical trials with dose 2.5-8 times higher than human therapeutic doses. These data indicate that OPAs detect phenotypic adversity and provide unique information that could useful towards safety testing during pharmaceutical development.
Related Links	http://dx.doi.org/10.1016/j.ntt.2014.11.002
Ending Page	53
Page Count	8
Starting Page	46
File Format	PDF
ISSN	08920362
e-ISSN	18729738
Journal	Neurotoxicology and teratology
Volume Number	47
Language	English
Publisher Date	2015-01-01
Access Restriction	Open
Subject Keyword	Toxicology Developmental Neuroscience Cellular and Molecular Neuroscience Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Toxicology Cellular and Molecular Neuroscience Developmental Neuroscience

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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