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The role of metabotropic glutamate receptor 5 (mGluR5) in stress\u2010induced psychopathology has been the target of several studies in humans. In rodents, blockade of mGluR5 produces antidepressant\u2010like actions, whereas mice lacking mGluR5 exhibit altered anxiety\u2010like behaviors and learning. In this study, we used well\u2010known rodent models of early life stress based on mother\u2013infant separation during the first 3\u2009weeks of life in order to examine the effects of neonatal maternal separation on mGluR5 expression and on anxiety\u2010related behavior in adulthood. We observed that brief (15\u2009min) neonatal maternal separation, but not prolonged (3\u00a0h), induced increases in mGluR5 mRNA and protein expression levels in medial prefrontal cortex and mGluR5 protein levels in dorsal, but not ventral, hippocampus of adult rat brain. Behavioral testing using the open\u2010field and the elevated\u2010plus maze tasks showed that brief maternal separations resulted in increased exploratory and decreased anxiety\u2010related behavior, whereas prolonged maternal separations resulted in increased anxiety\u2010related behavior in adulthood. The data indicate that the long\u2010lasting effects of neonatal mother\u2013offspring separation on anxiety\u2010like behavior and mGluR5 expression depend on the duration of maternal separation and suggest that the increased mGluR5 receptors in medial prefrontal cortex and hippocampus of adult rats exposed to brief neonatal maternal separations may underlie their heightened ability to cope with stress.<\/jats:p>","DOI":"10.1111\/ejn.15358","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T22:23:45Z","timestamp":1623882225000},"page":"4550-4564","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety\u2010related behavior of adult rats"],"prefix":"10.1111","volume":"54","author":[{"given":"Giota","family":"Tsotsokou","sequence":"first","affiliation":[{"name":"School of Health Sciences, 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