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MIA by prenatal exposure of polyinosinic:polycytidylic acid [poly(I:C)] in rodents caused behavioral and neurobiological changes relevant to schizophrenia in adult offspring. We investigated whether the novel antidepressant (<jats:italic>R<\/jats:italic>)-ketamine could prevent the development of psychosis-like phenotypes in adult offspring after MIA. We examined the effects of (<jats:italic>R<\/jats:italic>)-ketamine (10\u00a0mg\/kg\/day, twice weekly for 4\u00a0weeks) during juvenile and adolescent stages (P28\u2013P56) on the development of cognitive deficits, loss of parvalbumin (PV)-immunoreactivity in the medial prefrontal cortex (mPFC), and decreased dendritic spine density in the mPFC and hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, we examined the role of TrkB in the prophylactic effects of (<jats:italic>R<\/jats:italic>)-ketamine. Repeated intermittent administration of (<jats:italic>R<\/jats:italic>)-ketamine during juvenile and adolescent stages significantly blocked the development of cognitive deficits, reduced PV-immunoreactivity in the prelimbic (PrL) of mPFC, and decreased dendritic spine density in the PrL of mPFC, CA3 and dentate gyrus of the hippocampus from adult offspring after prenatal poly(I:C) exposure. Furthermore, pretreatment with ANA-12 (TrkB antagonist: twice weekly for 4\u00a0weeks) significantly blocked the beneficial effects of (<jats:italic>R<\/jats:italic>)-ketamine on cognitive deficits of adult offspring after prenatal poly(I:C) exposure. These data suggest that repeated intermittent administration of (<jats:italic>R<\/jats:italic>)-ketamine during juvenile and adolescent stages could prevent the development of psychosis in adult offspring after MIA. Therefore, (<jats:italic>R<\/jats:italic>)-ketamine would be a potential prophylactic drug for young subjects with high-risk for psychosis.<\/jats:p>","DOI":"10.1007\/s00406-021-01365-6","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:03:15Z","timestamp":1641168195000},"page":"693-701","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Repeated intermittent administration of (R)-ketamine during juvenile and adolescent stages prevents schizophrenia-relevant phenotypes in adult offspring after maternal immune activation: a role of TrkB signaling"],"prefix":"10.1007","volume":"272","author":[{"given":"Yunfei","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyu","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijia","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youge","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-0439","authenticated-orcid":false,"given":"Kenji","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"issue":"1","key":"1365_CR1","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1615\/CritRevNeurobiol.v14.i1.10","volume":"14","author":"B Elvev\u00e5g","year":"2000","unstructured":"Elvev\u00e5g B, Goldberg TE (2000) Cognitive impairment in schizophrenia is the core of the disorder. 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Dr. Hashimoto also declares that he has received research support and consultant from Dainippon Sumitomo, Otsuka, Taisho, Murakami Farm, and Perception Neuroscience. The other authors have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}