Prenatal treatment with methylazoxymethanol acetate as a neurodevelopmental disruption model of schizophrenia in mice
Autor: | Koichi Tan-No, Wakana Sakuma, Osamu Nakagawasai, Takayo Odaira, Kohei Takahashi, Jia-Rong Lin, Hiroshi Onogi, Lalit K. Srivastava, Wataru Nemoto |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Methylazoxymethanol Acetate medicine.drug_class Offspring Aripiprazole Atypical antipsychotic Hippocampus Motor Activity Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Pregnancy Internal medicine Haloperidol Animals Medicine Clozapine Prepulse inhibition Pharmacology Methylazoxymethanol acetate Behavior Animal Prepulse Inhibition business.industry Risperidone medicine.disease Disease Models Animal 030104 developmental biology Endocrinology chemistry Schizophrenia Prenatal Exposure Delayed Effects Female business 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug |
Zdroj: | Neuropharmacology. 150:1-14 |
ISSN: | 0028-3908 |
Popis: | Methylazoxymethanol (MAM)-treated pregnant rat at gestation day (GD) 17 has been shown to be a valuable developmental animal model for schizophrenia. Yet, this model remains to be established in mice. In the present study, we examined behavioral, cytoarchitectural, and neurochemical changes in the offspring of MAM-treated mice and validated the model's face, construct and predictive validities. We found that in contrast to a single injection of MAM to dams at GD 15, 16 or 17, its daily administration from GD 15 to 17 led to deficits in prepulse inhibition (PPI) of startle in the post-pubertal offspring. In addition, we observed behavioral deficits in working memory and social interactions, as well as an increase in locomotor activity induced by the NMDA antagonist MK-801 in GD15-17 MAM offspring. These animals also showed a reduction in the volume of the prefrontal cortex (PFC) and hippocampus, neuroanatomical changes such as discontinuities and heterotopias in the hippocampus, and an increase of DA level and DOPAC/DA ratio in the medial PFC. Atypical antipsychotic drugs clozapine, risperidone, and aripiprazole, but not the typical drug haloperidol, reversed the deficit in PPI and social withdrawal in the offspring of MAM-treated dams. In contrast, MK-801-induced hyperactivity in MAM mice was reversed by both and typical or atypical antipsychotic drugs. Taken together, the treatment of pregnant mice with MAM during GD 15-17 offers a new approach to study neurobiological mechanisms involved in the pathogenesis of schizophrenia. |
Databáze: | OpenAIRE |
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