Glucocorticoids are required for extinction of predator stress-induced hyperarousal

Clay, Rachel Laura Muriel (2010) Glucocorticoids are required for extinction of predator stress-induced hyperarousal. Masters thesis, Memorial University of Newfoundland.

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Abstract

Extinction of fearful behavior induced by severe stress was studied using predator stress. Predator stress involves a ten minute unprotected exposure of a rodent to a cat which induces long-lasting changes in anxiety-like behaviours and hyperarousal (increased acoustic startle response) (Adamec & Shallow, 1993; Adamec et al., 2001; Cohen et al., 2004). In the present set of experiments, three questions were addressed using predator stressed mice. First, can predator stress-induced fear memories be extinguished? Second, is the extinction of predator stress-induced fear memories glucocorticoid-dependent? Finally, is re-exposure to the predator stress context necessary to see glucocorticoid's effects on predator stress-induced fear memories? -- Extinction was induced by re-exposing mice to the predator stress room in the absence of the cat. This repeated re-exposure to predator stress context increased activity in the predator stress context implying extinction of predator stress-induced immobility, a context-dependent fear memory. Repeated re-exposures to the predator stress context also decreased subsequent hyperarousal (acoustic startle response) and generalized anxiety-like behaviour. These fearful behaviors were predator stress context independent, having been tested in environments different from the cat exposure room. Furthermore, blocking glucocorticoid synthesis with metyrapone during repeated exposures to the predator stress context had no effect on activity. Therefore, reducing corticosterone levels did not affect extinction of the predator stress-induced, context-dependent fear memory. However, metyrapone given during repeated exposures to the predator stress context prevented extinction of predator stress-induced hyperarousal. These results suggest that extinction of predator stress-induced, context-independent fear memory is dependent on the presence of endogenous corticosterone during the extinction trials. Finally, re-exposure to the predator stress context was found to be necessary to see glucocorticoid's effects on predator stress-induced fear memories. This was determined by repeated injection of metyrapone over days without re-exposure to the predator stress context.

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