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Early handling attenuates enhancement of glucocorticoid receptors in the prefrontal cortex in an animal model of post-traumatic stress disorder

Sophie A George1*, Stephanie A Stout1, Melissa Tan1, Dayan Knox13 and Israel Liberzon12

Author Affiliations

1 Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI 48109, USA

2 Ann Arbor Veterans Affairs Hospital, 2215 Fuller Road, Ann Arbor, MI 49105, USA

3 Present address: Department of Psychology, University of Delaware, 108 Wolf Hall, Newark, DE 19716, USA

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Biology of Mood & Anxiety Disorders 2013, 3:22  doi:10.1186/2045-5380-3-22

Published: 2 December 2013



Changes in glucocorticoid receptors (GRs) have been implicated in the pathogenesis of stress related psychiatric disorders such as depression and post-traumatic stress disorder (PTSD). Abnormal adaptation of the stress-response system following traumatic stress can lead to an altered hypothalamic-pituitary-adrenal axis that may contribute to PTSD development. Indeed, elevated GR expression in the hippocampus and prefrontal cortex linked to PTSD-like characteristics have been reported in the validated animal model of PTSD, single-prolonged stress. These findings implicate increased levels of GRs in the development of post-traumatic psychopathology and suggest that exploration of GR-targeted interventions may have potential for PTSD prevention. Early handling during the neonatal phase alters GR expression and is proposed to confer resilience to stress. We therefore examined the effects of combined early handling and single prolonged stress treatments on GR expression.


Timed pregnant dams gave birth to pups that were subjected to early handling (nā€‰=ā€‰11) or control (nā€‰=ā€‰13) procedures during the neonatal phase. At postnatal day 45 animals underwent single prolonged stress or a control procedure. Rats were euthanized one day later and GR levels were assayed using western blot electrophoresis.


Single prolonged stress exposure enhanced GR expression in the hippocampus and prefrontal cortex. Early handling treatment protected against single prolonged stress-induced enhancement of GR expression in the prefrontal cortex, but not in the hippocampus.


These data are a first step in highlighting the importance of targeting GR systems in prevention/resilience and may suggest that preventive strategies targeting GR upregulation might be particularly effective when prefrontal rather than hippocampal GRs are the target.

Hippocampus; HPA axis; Maternal care; Single prolonged stress; Stress