Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety‐related behavior of adult rats

• Published in: The European journal of neuroscience Vol. 54; no. 2; pp. 4550 - 4564
• Main Authors: Tsotsokou, Giota, Nikolakopoulou, Maria, Kouvelas, Elias D., Mitsacos, Ada
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.07.2021
• Subjects: Animal models; Animals; Anxiety; anxiety‐related behavior; Behavior; Gene expression; Glutamic acid receptors; Glutamic acid receptors (metabotropic); Hippocampus; Maternal behavior; Maternal Deprivation; maternal separation; medial prefrontal cortex; Mental depression; Mental disorders; metabotropic glutamate receptor 5; Mice; mRNA; neonatal handling; Neonates; Prefrontal cortex; Psychopathology; Rats; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5; Rodents; maternal separation; medial prefrontal cortex; anxiety-related behavior; hippocampus; metabotropic glutamate receptor 5; neonatal handling
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15358

Exposure to early life stress leads to long‐term neurochemical and behavioral alterations. Stress‐induced psychiatric disorders, such as depression, have recently been linked to dysregulation of glutamate signaling, mainly via its postsynaptic receptors. The role of metabotropic glutamate receptor 5 (mGluR5) in stress‐induced psychopathology has been the target of several studies in humans. In rodents, blockade of mGluR5 produces antidepressant‐like actions, whereas mice lacking mGluR5 exhibit altered anxiety‐like behaviors and learning. In this study, we used well‐known rodent models of early life stress based on mother–infant separation during the first 3 weeks of life in order to examine the effects of neonatal maternal separation on mGluR5 expression and on anxiety‐related behavior in adulthood. We observed that brief (15 min) neonatal maternal separation, but not prolonged (3 h), 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‐field and the elevated‐plus maze tasks showed that brief maternal separations resulted in increased exploratory and decreased anxiety‐related behavior, whereas prolonged maternal separations resulted in increased anxiety‐related behavior in adulthood. The data indicate that the long‐lasting effects of neonatal mother–offspring separation on anxiety‐like 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. Repeated 15‐min mother–offspring separations during the neonatal period result in resilience to stress and upregulation of mGluR5 expression in stress‐related brain regions during adulthood.