Tuesday, September 19, 2006

A treatment for acquired anxiety disorders in humans?

Cai et. al. show in a rodent model that administration of glucocorticoids immediately after reactivation of a contextual fear memory significantly diminishes subsequent recall of that fear memory. Glucocorticoids appear to both decrease fear memory retrieval and also augment consolidation of fear memory extinction.

The experiments used mice with a classical fear conditioning paradigm in which a novel environment is paired with footshock. Re-exposure to the training environment 48 hours later elicited significant fear responses, showing reactivation of a learned association between this environment and the aversive footshock stimulus. If the mice were injected 2 to 5 min after this reactivation with the endogenous stress hormone, corticosterone, they showed decreased contextual fear memory in subsequent tests.

Glucocorticoids have been used in human clinical trials to decrease symptoms of PTSD (post traumatic stress disorder) and phobia. The work of Cai et al. suggest that not only is the particular pharmacologic agent of importance, but that the reactivation of relevant memories, timing of administration relative to reactivation, and number of reactivation trials can have an impact on the desired outcome. The use of mice allows investigation of the underlying receptor subtypes and mechanisms of the glucocorticoid effect on fear memories. This might point to more specific therapy in future human trials that avoid some side effects of general treatment with glucocorticoids.

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