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Risperidone Administered During Asymptomatic Period of Adolescence Prevents the Emergence of Brain Structural Pathology and Behavioral Abnormalities in an Animal Model of Schizophrenia

Overview
Journal Schizophr Bull
Specialty Psychiatry
Date 2010 May 5
PMID 20439320
Citations 65
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Abstract

Schizophrenia is a disorder of a neurodevelopmental origin manifested symptomatically after puberty. Structural neuroimaging studies show that neuroanatomical aberrations precede onset of symptoms, raising a question of whether schizophrenia can be prevented. Early treatment with atypical antipsychotics may reduce the risk of transition to psychosis, but it remains unknown whether neuroanatomical abnormalities can be prevented. We have recently shown, using in vivo structural magnetic resonance imaging, that treatment with the atypical antipsychotic clozapine during an asymptomatic period of adolescence prevents the emergence of schizophrenia-like brain structural abnormalities in adult rats exposed to prenatal immune challenge, in parallel to preventing behavioral abnormalities. Here we assessed the preventive efficacy of the atypical antipsychotic risperidone (RIS). Pregnant rats were injected on gestational day 15 with the viral mimic polyriboinosinic-polyribocytidylic acid (poly I:C) or saline. Their male offspring received daily RIS (0.045 or 1.2 mg/kg) or vehicle injection in peri-adolescence (postnatal days [PND] 34-47). Structural brain changes and behavior were assessed at adulthood (from PND 90). Adult offspring of poly I:C-treated dams exhibited hallmark structural abnormalities associated with schizophrenia, enlarged lateral ventricles and smaller hippocampus. Both of these abnormalities were absent in the offspring of poly I:C dams that received RIS at peri-adolescence. This was paralleled by prevention of schizophrenia-like behavioral abnormalities, attentional deficit, and hypersensitivity to amphetamine in these offspring. We conclude that pharmacological intervention during peri-adolescence can prevent the emergence of behavioral abnormalities and brain structural pathology resulting from in utero insult. Furthermore, highly selective 5HT(2A) receptor antagonists may be promising targets for psychosis prevention.

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References
1.
Arnt J, Skarsfeldt T . Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology. 1998; 18(2):63-101. DOI: 10.1016/S0893-133X(97)00112-7. View

2.
Choi Y, Moran-Gates T, Gardner M, Tarazi F . Effects of repeated risperidone exposure on serotonin receptor subtypes in developing rats. Eur Neuropsychopharmacol. 2009; 20(3):187-94. PMC: 2819571. DOI: 10.1016/j.euroneuro.2009.09.002. View

3.
Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee B, Feldon J . Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacology. 2007; 33(2):441-56. DOI: 10.1038/sj.npp.1301413. View

4.
Jarskog L, Miyamoto S, Lieberman J . Schizophrenia: new pathological insights and therapies. Annu Rev Med. 2006; 58:49-61. DOI: 10.1146/annurev.med.58.060904.084114. View

5.
Wolf O, Dyakin V, Vadasz C, de Leon M, McEwen B, Bulloch K . Volumetric measurement of the hippocampus, the anterior cingulate cortex, and the retrosplenial granular cortex of the rat using structural MRI. Brain Res Brain Res Protoc. 2002; 10(1):41-6. DOI: 10.1016/s1385-299x(02)00181-2. View