title: Prenatal exposure to a novel antipsychotic quetiapine: impact on neuro-architecture, apoptotic neurodegeneration in fetal hippocampus and cognitive impairment in young rats.
abstract: Reports on prenatal exposure to some of the first generation antipsychotic drugs like, haloperidol, their effects on fetal neurotoxicity and functional impairments in the offspring, are well documented. But studies on in utero exposure to second generation antipsychotics, especially quetiapine, and its effects on fetal neurotoxicity, apoptotic neurodegeneration, postnatal developmental delay and neurobehavioral consequences are lacking. Therefore, the present study was undertaken to evaluate the effect of prenatal administration to equivalent therapeutic doses of quetiapine on neuro-architectural abnormalities, neurohistopathological changes, apoptotic neurodegeneration in fetal hippocampus, and postnatal development and growth as well as its long-lasting imprint on cognitive impairment in young-adult offspring. Pregnant Wistar rats (n=24) were exposed to selected doses (55 mg, 80 mg and 100mg/kg) of quetiapine, equivalent to human therapeutic doses, from gestation day 6 to 21 orally with control subjects. Half of the pregnant subjects of each group were sacrificed at gestation day 21 for histopathological, confocal and electron microscopic studies and rest of the dams were allowed to deliver naturally. Their pups were reared postnatally up to 10 weeks of age for neurobehavioral observations. In quetiapine treated groups, there was significant alterations in total and differential thickness of three typical layers of hippocampus associated with neuronal cells deficit and enhanced apoptotic neurodegeneration in the CA1 area of fetal hippocampus. Prenatally drug treated rat offspring displayed post-natal developmental delay till postnatal day 70, and these young-adult rats displayed cognitive impairment in Morris water maze and passive avoidance regimes as long-lasting impact of the drug. Therefore, quetiapine should be used with cautions considering its developmental neurotoxicological and neurobehavioral potential in animal model, rat.
authors.affiliation: Neurobiology Laboratory, Department of Zoology, University of Allahabad, Allahabad 211 002, India. Electronic address: kpsald29@gmail.com.
authors.forename: K P
authors.initials: KP
authors.lastname: Singh
authors.affiliation: Neurobiology Laboratory, Department of Zoology, University of Allahabad, Allahabad 211 002, India. Electronic address: nidhitripathi044@gmail.com.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Tripathi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001362:Avoidance Learning / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000196:embryology / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008854:Microscopy, Electron; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D000069348:Quetiapine Fumarate / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014150:Antipsychotic Agents; D000069348:Quetiapine Fumarate
keywords: Antipsychotics; Apoptosis; Cognition; Prenatal; Quetiapine; Rat