Neuroplastic Correlates in the mPFC Underlying the Impairment of Stress-Coping Ability and Cognitive Flexibility in Adult Rats Exposed to Chronic Mild Stress during Adolescence.
Using a valid chronic mild stress (CMS) model of depression, we found that adolescent (postnatal days [PND] 28-41) CMS induced transient alterations in anhedonia that did not persist into adulthood after a 3-week recovery period. Previously stressed adult rats exhibited more immobility/despair behaviors in the forced swimming test and a greater number of trials to reach criterion in the set-shifting task, suggesting the impaired ability to cope with stressors and the cognitive flexibility that allows adaptation to dynamic environments during adulthood. In addition, adult rat exposure to adolescent CMS had a relatively inhibited activation in ERK signaling and downstream protein expression of phosphorylated cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex. Further correlation analysis demonstrated that immobility and set-shifting performance were positively correlated with the inhibition of ERK signaling. These results indicated adolescent CMS can be used as an effective stressor to model an increased predisposition to adult depression.
CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; The University of Chinese Academy of Sciences, Beijing, China; School of Nursing, Binzhou Medical University, Yantai, China.
Yu
Y
Zhang
School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China.
Feng
F
Shao
School of Psychological and Cognitive Sciences, Beijing Key Laboratory of Behavior and Mental Health, Peking University, Beijing, China.
Qiong
Q
Wang
CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; The University of Chinese Academy of Sciences, Beijing, China.
Xi
X
Xie
CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China.
Weiwen
0000-0001-9231-6106
W
Wang
D000223:Adaptation, Psychological; D000818:Animals; D001288:Attention; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D003214:Conditioning, Classical; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003866:Depressive Disorder / Q000209:etiology / Q000378:metabolism* / Q000523:psychology*; D004195:Disease Models, Animal; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009473:Neuronal Plasticity; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications*
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3