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Accession Number ADA574088
Title Medial Prefrontal Cortex and HPA Axis Roles in Generation of PTSD-Like Symptoms in SPS Model.
Publication Date Sep 2012
Media Count 68p
Personal Author I. Liberzon S. A. George
Abstract Neurobiological research has implicated abnormalities in medial prefrontal cortical function (mPFC), as well as altered hypothalamus-pituitary- adrenal (HPA) axis function in Post-traumatic stress disorder, but the mechanisms that link PTSD symptom generation, mPFC medial function, and stress axis abnormalities have not been established. PTSD s clinical manifestation includes intrusive recollections of the traumatic event, avoidance of social interactions, and a failure to regulate fear and anxiety. We used the Single Prolonged Stress (SPS) model to examine the effect of SPS on HPA and mPFC function and how this relates to specific PTSD symptoms. Our data suggest that SPS animals have disruptions in the retention of extinction memories, and that augmentation of GR expression in the PFC and hippocampus is linked to SPS- induced extinction retention deficits. SPS animals also have decreased levels of glutamate in the mPFC, suggesting decreased excitatory neurotransmission in a brain region critical for emotion regulation. In addition, we have also demonstrated enhanced noradrenergic reactivity in the locus coeruleus of SPS rats using electrophysiological recording and TH mRNA levels. Preliminary findings relating to social interaction in SPS animals have not been robust or consistent, but we have demonstrated that some SPS effects can be attenuated by increasing mother-pup social interactions, and that inactivation of the BLA attenuates social interactions. We also found that SPS impairs another form of behavioral regulation, cognitive flexibility. During the funding period we have made significant advances in understanding neurobiological responses to trauma, linking specific behavioral changes to changes in HPA axis, and finding evidence of changes in glutamatergic transmission and noradrenergic system activity.
Keywords Abnormalities
Adrenal cortex
Clinical medicine
Hpa(Hypothalamus- pituitary-adrenal)
Mpfc(Medial prefrontal cortical function)
Order disorder transformations
Pituitary gland
Post traumatic stress disorder
Prefrontal cortex
Sps(Single prolonged stress)

Source Agency Non Paid ADAS
NTIS Subject Category 92B - Psychology
57T - Psychiatry
57E - Clinical Medicine
Corporate Author Michigan Univ., Ann Arbor.
Document Type Technical report
Title Note Final rept. 1 Sep 2008-31 Aug 2012.
NTIS Issue Number 1318
Contract Number W81XWH-08-1-0661

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