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It is an important therapeutic option in the treatment of perinatal depression, but the effects of VEN on fetus and the newborn are uncertain. Therefore, present study was undertaken to investigate the safety of <jats:italic>in\u2010utero<\/jats:italic> exposure to VEN in terms of developmental neurotoxicity and neurodegenerative potential by using prenatal rat model. The selected doses of VEN (25, 40 and 50 mg\/kg) were administered to pregnant rats from GD 5 to 19 through oral gavage. The fetal brains were dissected and processed for histopathological measurements of neocortical thickness that showed significant reduction. Considering vulnerability of immature brain to free radical injury, VEN exposed neocortices were tested for reactive oxygen species (ROS) levels which were significantly increased. As ROS play important role in the initiation of apoptotic mechanisms, we explored for <jats:italic>in situ<\/jats:italic> detection of apoptosis by confocal microscopy that showed enhanced apoptosis including chromatin condensation which was further reconfirmed by electron microscopy. Substantially increased levels of pro\u2010apoptotic protein Bax and decreased levels of anti\u2010apoptotic protein Bcl2 as shown by western blotting also supported the increased neuro\u2010apoptotic degeneration. For further correlation of these findings, prenatally VEN exposed young\u2010adult rat offspring were assessed for open field exploratory behavior that showed increased anxiety\u2010like and stereotypic responses indicating disturbed neurobehavioral pattern. The study concludes that prenatal VEN exposure may primarily enhance ROS generation that plays a key role in regulating release of proapoptotic factors from mitochondria and thereby enhancing apoptotic neurodegeneration that affect proliferation, migration and differentiation of cells, resulting in neuronal deficits manifested as long term neurobehavioral impairments.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2014.10.007","type":"journal-article","created":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T01:15:03Z","timestamp":1416186903000},"page":"60-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Assessment of <i>in\u2010utero<\/i> venlafaxine induced, ROS\u2010mediated, apoptotic neurodegeneration in fetal neocortex and neurobehavioral sequelae in rat offspring"],"prefix":"10.1002","volume":"40","author":[{"given":"Manish","family":"Singh","sequence":"first","affiliation":[{"name":"Institute of Nano Science and Technology Mohali India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Neurobiology Lab Department of Zoology University of Allahabad Allahabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shubha","family":"Shukla","sequence":"additional","affiliation":[{"name":"CSIR\u2010Central Drug Research Institute Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhu","family":"Dikshit","sequence":"additional","affiliation":[{"name":"CSIR\u2010Central Drug Research Institute Lucknow India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,11,13]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Atlas of Prenatal Rat Brain Development","author":"Altman J.","year":"1994"},{"issue":"5697","key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1126\/science.1101678","article-title":"Early\u2010life blockade of the 5\u2010HT transporter alters emotional behavior in adult mice","volume":"306","author":"Ansorge M.S.","year":"2004","journal-title":"Science"},{"issue":"1","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/01.jcp.0000194622.99986.d6","article-title":"Mirtazapine orally disintegrating tablets versus venlafaxine extended release: a double\u2010blind, randomized multicenter trial comparing the onset of antidepressant response in patients with major depressive disorder","volume":"26","author":"Benkert O.","year":"2006","journal-title":"J. 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