Olanzapine treatment of adolescent rats causes enduring specific memory impairments and alters cortical development and function

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dc.contributor.authorMilstein, Jean A.
dc.contributor.authorElnabawi, Ahmed
dc.contributor.authorVinish, Monika
dc.contributor.authorSwanson, Thomas
dc.contributor.authorEnos, Jennifer K.
dc.contributor.authorBailey, Aileen M.
dc.contributor.authorKolb, Bryan
dc.contributor.authorFrost, Douglas O.
dc.date.accessioned2016-11-22T19:22:51Z
dc.date.available2016-11-22T19:22:51Z
dc.date.issued2013
dc.descriptionSherpa Romeo green journal: open accessen_US
dc.description.abstractAntipsychotic 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 drugsen_US
dc.description.peer-reviewYesen_US
dc.identifier.citationMilstein, 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.0057308en_US
dc.identifier.urihttps://hdl.handle.net/10133/4725
dc.language.isoen_CAen_US
dc.publisherPublic Library of Scienceen_US
dc.publisher.departmentDepartment of Neuroscienceen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Maryland School of Medicineen_US
dc.publisher.institutionSt. Mary's College of Marylanden_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.subjectOlanzapineen_US
dc.subjectMemory impairmenten_US
dc.subjectCortical developmenten_US
dc.subjectCortical functionen_US
dc.subjectAntipsychotic drugsen_US
dc.subjectMemory disordersen_US
dc.subjectAdolescent APD treatmenten_US
dc.subjectPediatric APD treatmenten_US
dc.titleOlanzapine treatment of adolescent rats causes enduring specific memory impairments and alters cortical development and functionen_US
dc.typeArticleen_US
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