European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
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Eur Neuropsychopharmacol · Nov 2009
A distinct pattern of intracellular glucocorticoid-related responses is associated with extreme behavioral response to stress in an animal model of post-traumatic stress disorder.
Activation of glucocorticoid receptors (GR) increases expression of the mitogen-activated protein kinase (MAPK) pathway leading to increased expression of Zif/268, an effector immediate early gene involved in cellular growth, intracellular signaling, and synaptic modification. Glucocorticoids induce expression of Zif/268 through two distinct mechanisms: a rapid-onset, MAPK-independent pathway and a slower-onset, MAPK-dependent mechanism. ⋯ Following the uniform acute response, the patterns of GR protein levels and Zif/268 mRNA levels are associated with degree of behavioral disruption. Since the slower-onset mechanism for glucocorticoid-induced Zif/268 expression depends on activation of the MAPK pathway, the pattern observed only in EBR rats may be related to disruptions of this pathway.