Background: Changes in glucocorticoid receptors (GRs) have been implicated in the pathogenesis of stress related\r\npsychiatric disorders such as depression and post-traumatic stress disorder (PTSD). Abnormal adaptation of the\r\nstress-response system following traumatic stress can lead to an altered hypothalamic-pituitary-adrenal axis that\r\nmay contribute to PTSD development. Indeed, elevated GR expression in the hippocampus and prefrontal cortex\r\nlinked to PTSD-like characteristics have been reported in the validated animal model of PTSD, single-prolonged\r\nstress. These findings implicate increased levels of GRs in the development of post-traumatic psychopathology and\r\nsuggest that exploration of GR-targeted interventions may have potential for PTSD prevention. Early handling\r\nduring the neonatal phase alters GR expression and is proposed to confer resilience to stress. We therefore\r\nexamined the effects of combined early handling and single prolonged stress treatments on GR expression.\r\nMethods: Timed pregnant dams gave birth to pups that were subjected to early handling (n = 11) or control\r\n(n = 13) procedures during the neonatal phase. At postnatal day 45 animals underwent single prolonged stress or a\r\ncontrol procedure. Rats were euthanized one day later and GR levels were assayed using western blot\r\nelectrophoresis.\r\nResults: Single prolonged stress exposure enhanced GR expression in the hippocampus and prefrontal cortex. Early\r\nhandling treatment protected against single prolonged stress-induced enhancement of GR expression in the\r\nprefrontal cortex, but not in the hippocampus.\r\nConclusions: These data are a first step in highlighting the importance of targeting GR systems in prevention/\r\nresilience and may suggest that preventive strategies targeting GR upregulation might be particularly effective\r\nwhen prefrontal rather than hippocampal GRs are the target.
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