Olanzapine antipsychotic treatment of adolescent rats causes long term changes in glutamate and GABA levels in the nucleus accumbens.


:Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28-49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and γ-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's "reward" system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients.


Schizophr Res


Schizophrenia research


Xu S,Gullapalli RP,Frost DO




Has Abstract


2015-02-01 00:00:00














  • Effect of antipsychotic treatment on Insulin-like Growth Factor-1 and cortisol in schizophrenia: a longitudinal study.

    abstract::Neurodevelopmental pathogenesis of schizophrenia might be mediated by abnormalities in Insulin-like Growth Factor-1 (IGF-1). Developmental disturbances like obstetric complications, by themselves, as well as through the resultant hypercortisolemia due to hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, can lea...

    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Venkatasubramanian G,Chittiprol S,Neelakantachar N,Shetty T,Gangadhar BN

    更新日期:2010-06-01 00:00:00

  • Comorbid posttraumatic stress disorder is associated with suicidality in male veterans with schizophrenia or schizoaffective disorder.

    abstract::The purpose of this study was to determine if patients with schizophrenia or schizoaffective disorders and comorbid posttraumatic stress disorder (PTSD) are at higher risk for suicidality than patients without comorbid PTSD. Participants were 165 male veterans with primary diagnoses of schizophrenia or schizoaffective...

    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Strauss JL,Calhoun PS,Marx CE,Stechuchak KM,Oddone EZ,Swartz MS,Butterfield MI

    更新日期:2006-05-01 00:00:00

  • A clinical trial of the effects of estrogen in acutely psychotic women.

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    journal_title:Schizophrenia research

    pub_type: 临床试验,杂志文章


    authors: Kulkarni J,de Castella A,Smith D,Taffe J,Keks N,Copolov D

    更新日期:1996-07-05 00:00:00

  • Antipsychotic treatment patterns and hospitalizations among adults with schizophrenia.

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: dosReis S,Johnson E,Steinwachs D,Rohde C,Skinner EA,Fahey M,Lehman AF

    更新日期:2008-04-01 00:00:00

  • Genetically determined schizophrenia is not associated with impaired glucose homeostasis.

    abstract::Here, we used data from large genome-wide association studies to test the presence of causal relationships, conducting a Mendelian randomization analysis; and shared molecular mechanisms, calculating the genetic correlation, among schizophrenia, type 2 diabetes (T2D), and impaired glucose homeostasis. Although our Men...

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    pub_type: 杂志文章


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    更新日期:2018-05-01 00:00:00

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    abstract:OBJECTIVE:The main goal of the present study was to analyze levels of cytokines of the interleukin family (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8 and IL-10), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor-alpha (TNF-α), and vascular endothelial and endothelial growth factors (V...

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    pub_type: 杂志文章


    authors: Haring L,Koido K,Vasar V,Leping V,Zilmer K,Zilmer M,Vasar E

    更新日期:2015-12-01 00:00:00

  • Stress and arousability in schizophrenia.

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    pub_type: 杂志文章


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    更新日期:2004-11-01 00:00:00

  • Effects of clozapine, fluphenazine, and placebo on reaction time measures of attention and sensory dominance in schizophrenia.

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    pub_type: 临床试验,杂志文章,随机对照试验


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    更新日期:1994-09-01 00:00:00

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Valiente C,Provencio M,Espinosa R,Duque A,Everts F

    更新日期:2015-05-01 00:00:00

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    authors: Goldstein KE,Hazlett EA,New AS,Haznedar MM,Newmark RE,Zelmanova Y,Passarelli V,Weinstein SR,Canfield EL,Meyerson DA,Tang CY,Buchsbaum MS,Siever LJ

    更新日期:2009-07-01 00:00:00

  • Resequencing of the vesicular glutamate transporter 2 gene (VGLUT2) reveals some rare genetic variants that may increase the genetic burden in schizophrenia.

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    journal_title:Schizophrenia research

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    authors: Shen YC,Liao DL,Lu CL,Chen JY,Liou YJ,Chen TT,Chen CH

    更新日期:2010-08-01 00:00:00

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    pub_type: 杂志文章,meta分析


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    更新日期:2012-05-01 00:00:00

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    pub_type: 杂志文章,评审


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    更新日期:2018-08-01 00:00:00

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    更新日期:2017-09-01 00:00:00

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    更新日期:2009-12-01 00:00:00

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    pub_type: 杂志文章,评审


    authors: Manoach DS

    更新日期:2003-04-01 00:00:00

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Harvey PD,Sukhodolsky D,Parrella M,White L,Davidson M

    更新日期:1997-10-30 00:00:00

  • Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7.

    abstract::Viral infections during fetal and adolescent periods, as well as during the course of schizophrenia itself have been linked to the onset and/or relapse of a psychosis. We previously reported that the unique antipsychotic aripiprazole, a partial D2 agonist, inhibits the release of tumor necrosis factor (TNF)-α from int...

    journal_title:Schizophrenia research

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    authors: Sato-Kasai M,Kato TA,Ohgidani M,Mizoguchi Y,Sagata N,Inamine S,Horikawa H,Hayakawa K,Shimokawa N,Kyuragi S,Seki Y,Monji A,Kanba S

    更新日期:2016-12-01 00:00:00

  • Compensatory cognitive training for people with severe mental illnesses in supported employment: A randomized controlled trial.

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    journal_title:Schizophrenia research

    pub_type: 杂志文章,随机对照试验


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    更新日期:2019-01-01 00:00:00

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    authors: Kelleher I,Wigman JT,Harley M,O'Hanlon E,Coughlan H,Rawdon C,Murphy J,Power E,Higgins NM,Cannon M

    更新日期:2015-06-01 00:00:00

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    pub_type: 杂志文章


    authors: Semkovska M,Bédard MA,Godbout L,Limoge F,Stip E

    更新日期:2004-08-01 00:00:00

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


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    更新日期:2009-07-01 00:00:00

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    authors: Kane JM,Skuban A,Ouyang J,Hobart M,Pfister S,McQuade RD,Nyilas M,Carson WH,Sanchez R,Eriksson H

    更新日期:2015-05-01 00:00:00

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Havermans R,Honig A,Vuurman EF,Krabbendam L,Wilmink J,Lamers T,Verheecke CJ,Jolles J,Romme MA,van Praag HM

    更新日期:1999-08-17 00:00:00

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    pub_type: 杂志文章


    authors: Devoe DJ,Lu L,Cannon TD,Cadenhead KS,Cornblatt BA,McGlashan TH,Perkins DO,Seidman LJ,Tsuang MT,Woods SW,Walker EF,Mathalon DH,Bearden CE,Addington J

    更新日期:2020-04-30 00:00:00

  • Executive functions in adolescents with schizotypal personality disorder.

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Diforio D,Walker EF,Kestler LP

    更新日期:2000-04-07 00:00:00

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Leeson VC,Laws KR,McKenna PJ

    更新日期:2006-12-01 00:00:00

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    journal_title:Schizophrenia research

    pub_type: 杂志文章,随机对照试验


    authors: Chang WC,Kwong VW,Chan GH,Jim OT,Lau ES,Hui CL,Chan SK,Lee EH,Chen EY

    更新日期:2016-05-01 00:00:00

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    journal_title:Schizophrenia research

    pub_type: 杂志文章


    authors: Domínguez E,Loza MI,Padín F,Gesteira A,Paz E,Páramo M,Brenlla J,Pumar E,Iglesias F,Cibeira A,Castro M,Caruncho H,Carracedo A,Costas J

    更新日期:2007-02-01 00:00:00