Role of Noradrenergic Signaling in the Basolateral Amygdala in Habituation to Repeated Stress.

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is an important stress-responsive system, but overactivity of the HPA axis can be detrimental to the physiological and psychological health of the organism. HPA activity habituates with repeated exposure to a homotypic stressor to limit these negative health consequences. HPA activation to habituating stressors occurs via limbic brain structures, though the exact mechanisms are unknown. One limbic structure, the basolateral amygdala (BLA), is well known as a mediator of learning and memory for aversive events. In particular, noradrenergic signaling via the beta-adrenergic receptor (beta-AR) in the BLA can bidirectionally modulate memory for an aversive experience. I hypothesized that similar mechanisms in the BLA may regulate HPA habituation to a stressor. In this dissertation, I found that beta-AR manipulations in the BLA after daily restraint bidirectionally modified the strength of habituation to restraint. Beta-AR blockade in the BLA prevented restraint-induced changes in gene expression in the hypothalamus and BLA. Beta-AR blockade also attenuated restraint-induced changes in intracellular signaling in the BLA, and these changes in signaling exert direct control of HPA activity to restraint. These findings 1) demonstrate the importance of beta-AR signaling in repeated restraint, 2) suggest that current models of beta-AR function in the BLA need to be revised, and 3) suggest that habituation to repeated stressors has important similarities and differences to models of aversive conditioning.