The influence of later-life stress on the neural regulation of fear and anxiety
Most investigations into the neural regulation of anxiety are conducted using naïve animals as subjects and, typically involve tests that measure animals' normal, presumably adaptive responses to aversive stimuli. However, periods of stress often precede and, in fact, may precipitate the excessive or inappropriate levels of fear and anxiety that are manifest in human anxiety disorders. Thus, it seems critical to include an element of prior stress exposure in any research program that aims to unravel the neural mechanisms of anxiety. In particular, this might allow us to determine how stress can lead to excessive or contextually inappropriate fear responses. For example, I recently found that chronic variable stress dramatically increases rats' fear expression in the shock-probe burying test. Furthermore, the effects of long-term administration of the anti-depressant agent fluoxetine on fear expression were heavily influenced by the prior stress history of the rat, suggesting that stress also alters the organism's sensitivity to the therapeutic actions of these compounds.
In the future, I plan to continue investigating the effects of prior stress (and subsequent pharmacological treatments) on behavioral reactivity in animal tests of fear or anxiety and mapping these changes onto changes in receptor binding properties and the expression of gene products in brain. These studies could provide valuable insight into the etiology of stress-related disorders and may promote the development of better pharmacological agents for treating these debilitating disorders.
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