PMID- 29166674 OWN - NLM STAT- MEDLINE DCOM- 20171211 LR - 20191210 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 11 DP - 2017 TI - Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains. PG - e0188537 LID - 10.1371/journal.pone.0188537 [doi] LID - e0188537 AB - Alterations in the social and cognitive domain are considered important indicators for increased disability in many stress-related disorders. Similar impairments have been observed in rodents chronically exposed to stress, mimicking potential endophenotypes of stress-related psychopathologies such as major depression disorder (MDD), anxiety, conduct disorder, and posttraumatic stress disorder (PTSD). Data from numerous studies suggest that deficient plasticity mechanisms in hippocampus (HC) and prefrontal cortex (PFC) might underlie these social and cognitive deficits. Specifically, stress-induced deficiencies in neural plasticity have been associated with a hypodopaminergic state and reduced neural plasticity persistence. Here we assessed the effects of unpredictable chronic mild stress (UCMS) on exploratory, social and cognitive behavior of females of two inbred mouse strains (C57BL/6J and DBA/2J) that differ in their dopaminergic profile. Exposure to chronic stress resulted in impaired circadian rhythmicity, sociability and social cognition in both inbred strains, but differentially affected activity patterns and contextual discrimination performance. These stress-induced behavioral impairments were accompanied by reduced expression levels of brain derived neurotrophic factor (BDNF) in the prefrontal cortex. The strain-specific cognitive impairment was coexistent with enhanced plasma corticosterone levels and reduced expression of genes related to dopamine signaling in hippocampus. These results underline the importance of assessing different strains with multiple test batteries to elucidate the neural and genetic basis of social and cognitive impairments related to chronic stress. FAU - van Boxelaere, Michiel AU - van Boxelaere M AD - Laboratory of Biological Psychology, KU Leuven, Leuven, Belgium. FAU - Clements, Jason AU - Clements J AD - Laboratory of Behavioral and Developmental Genetics, KU Leuven, Leuven, Belgium. FAU - Callaerts, Patrick AU - Callaerts P AD - Laboratory of Behavioral and Developmental Genetics, KU Leuven, Leuven, Belgium. FAU - D'Hooge, Rudi AU - D'Hooge R AD - Laboratory of Biological Psychology, KU Leuven, Leuven, Belgium. AD - Leuven Research Institute for Neuroscience & Disease (LIND), Leuven, Belgium. FAU - Callaerts-Vegh, Zsuzsanna AU - Callaerts-Vegh Z AUID- ORCID: 0000-0001-9091-2078 AD - Laboratory of Biological Psychology, KU Leuven, Leuven, Belgium. AD - Leuven Research Institute for Neuroscience & Disease (LIND), Leuven, Belgium. AD - mINT Mouse Behavioral Core Facility, KULeuven, Leuven, Belgium. LA - eng PT - Journal Article DEP - 20171122 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Biomarkers) RN - 0 (RNA, Messenger) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - W980KJ009P (Corticosterone) SB - IM MH - Animals MH - Anxiety MH - *Behavior, Animal MH - Biomarkers/blood MH - Body Weight MH - Chronic Disease MH - Conditioning, Psychological MH - Corticosterone/blood MH - *Discrimination Learning MH - Exploratory Behavior MH - Female MH - Gene Expression Regulation MH - Hippocampus/metabolism MH - Mice, Inbred C57BL MH - Mice, Inbred DBA MH - RNA, Messenger/genetics/metabolism MH - *Social Behavior MH - Stress, Psychological/genetics/*pathology MH - Tyrosine 3-Monooxygenase/genetics/metabolism PMC - PMC5699833 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/11/23 06:00 MHDA- 2017/12/12 06:00 PMCR- 2017/11/22 CRDT- 2017/11/23 06:00 PHST- 2017/08/11 00:00 [received] PHST- 2017/11/08 00:00 [accepted] PHST- 2017/11/23 06:00 [entrez] PHST- 2017/11/23 06:00 [pubmed] PHST- 2017/12/12 06:00 [medline] PHST- 2017/11/22 00:00 [pmc-release] AID - PONE-D-17-29782 [pii] AID - 10.1371/journal.pone.0188537 [doi] PST - epublish SO - PLoS One. 2017 Nov 22;12(11):e0188537. doi: 10.1371/journal.pone.0188537. eCollection 2017.