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dc.contributor.author Milstein, Jean A.
dc.contributor.author Elnabawi, Ahmed
dc.contributor.author Vinish, Monika
dc.contributor.author Swanson, Thomas
dc.contributor.author Enos, Jennifer K.
dc.contributor.author Bailey, Aileen M.
dc.contributor.author Kolb, Bryan
dc.contributor.author Frost, Douglas O.
dc.date.accessioned 2016-11-22T19:22:51Z
dc.date.available 2016-11-22T19:22:51Z
dc.date.issued 2013
dc.identifier.citation Milstein, J. A., Elnabawi, A., Vinish, M., Swanson, T., Enos, J. K., Bailey, A. M., ... & Frost, D. O. (2013). Olanzapine treatment of adolescent rats causes enduring specific memory impairments and alters cortical development and function. PLoS ONE, 8(2), e57308. doi:10.1371/journal.pone.0057308 en_US
dc.identifier.uri https://hdl.handle.net/10133/4725
dc.description Sherpa Romeo green journal: open access en_US
dc.description.abstract Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug treatment. Most antipsychotic drugs are potent antagonists or partial agonists of dopamine D2 receptors; atypical antipsychotic drugs also antagonize type 2A serotonin receptors. Dopamine and serotonin regulate many neurodevelopmental processes. Thus, early life antipsychotic drug treatment can, potentially, perturb these processes, causing long-term behavioral- and neurobiological impairments. Here, we treated adolescent, male rats with olanzapine on post-natal days 28–49. As adults, they exhibited impaired working memory, but normal spatial memory, as compared to vehicle-treated control rats. They also showed a deficit in extinction of fear conditioning. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbitaland medial prefrontal cortices, parietal cortex, nucleus accumbens core and dentate gyrus, adolescent olanzapine treatment altered the developmental dynamics and mature values of dendritic spine density in a region-specific manner. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, D1 binding was reduced and binding of GABAA receptors with open Cl2 channels was increased. In medial prefrontal cortex, D2 binding was also increased. The persistence of these changes underscores the importance of improved understanding of the enduring sequelae of pediatric APD treatment as a basis for weighing the benefits and risks of adolescent antipsychotic drug therapy, especially prophylactic treatment in high risk, asymptomatic patients. The long-term changes in neurotransmitter receptor binding and neural circuitry induced by adolescent APD treatment may also cause enduring changes in behavioral- and neurobiological responses to other therapeutic- or illicit psychotropic drugs en_US
dc.language.iso en_CA en_US
dc.publisher Public Library of Science en_US
dc.subject Olanzapine en_US
dc.subject Memory impairment en_US
dc.subject Cortical development en_US
dc.subject Cortical function en_US
dc.subject Antipsychotic drugs en_US
dc.subject Memory disorders en_US
dc.subject Adolescent APD treatment en_US
dc.subject Pediatric APD treatment en_US
dc.title Olanzapine treatment of adolescent rats causes enduring specific memory impairments and alters cortical development and function en_US
dc.type Article en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Neuroscience en_US
dc.description.peer-review Yes en_US
dc.publisher.institution University of Maryland School of Medicine en_US
dc.publisher.institution St. Mary's College of Maryland en_US
dc.publisher.institution University of Lethbridge en_US


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