title: Mifepristone Treatment during Early Adolescence Fails to Restore Maternal Deprivation-Induced Deficits in Behavioral Inhibition of Adult Male Rats.
abstract: Early life adversity has a profound impact on brain development and later life health. Animal models have provided insight how early life stress programs stress responsiveness and might contribute to the development of psychiatric disorders. In the present study, the long-term effects of maternal deprivation (MD) on behavioral inhibition and attention were examined in adult male Wistar rats. To this end animals were tested in the 5-choice serial reaction time task (5-choice SRTT). We also explored the potential of a 3-day treatment with the glucocorticoid receptor (GR) antagonist mifepristone during early adolescence to normalize putative behavioral effects of early life stress. Deprivation of the mother for 24 h on postnatal day (PND) 3 led to a modest but significant increase in premature responses in the 5-choice SRTT, but did not affect measures of attention. Body weight was lower in deprived animals from weaning until the start of testing. Early adolescent mifepristone treatment (PND 26-28) did not influence performance on the 5-choice SRTT and did not mitigate the deprivation-related impairment in behavioral inhibition. Our results indicate that MD leads to impaired behavioral inhibition, and that mifepristone treatment during early adolescence does not normalize the behavioral changes caused by early life stress.
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Jiska
authors.initials: J
authors.lastname: Kentrop
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Liza
authors.initials: L
authors.lastname: van der Tas
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Manila
authors.initials: M
authors.lastname: Loi
authors.affiliation: Centre for Child and Family Studies, Leiden University Leiden, Netherlands.
authors.forename: Marinus H
authors.initials: MH
authors.lastname: van IJzendoorn
authors.affiliation: Centre for Child and Family Studies, Leiden University Leiden, Netherlands.
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Bakermans-Kranenburg
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht Utrecht, Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joëls
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center UtrechtUtrecht, Netherlands; Centre for Child and Family Studies, Leiden UniversityLeiden, Netherlands.
authors.forename: Rixt
authors.initials: R
authors.lastname: van der Veen
keywords: 5-choice serial reaction time task; adolescence; attention; early life stress; impulsivity; maternal deprivation; mifepristone