Chronic stress-induced alterations in amygdala responsiveness and behavior--modulation by trait anxiety and corticotropin-releasing factor systems.

The basolateral nucleus of the amygdala (BLA) plays a key role in emotional arousal and anxiety, and expresses high levels of corticotropin-releasing factor receptor (CRFR)1. In rat brain slices, we have recently shown that afferent activation of the BLA is increased following application of exogenous corticotropin-releasing factor (CRF). Here we examined the impact of chronic unpredictable stress (CUS) on this effect of CRF and whether blockade of CRFR1 could prevent stress-induced changes in the electrophysiological response, the animal's behavior and in cell proliferation in the hippocampus. The behavior of the rats was monitored via a series of tests that formed part of the CUS. Electrophysiological measures of the BLA response to CRF, cell proliferation in the dentate gyrus and the expression of CRF and CRFR1 mRNA in amygdaloid nuclei were determined ex vivo after completion of the CUS. CRF-induced potentiation of afferent activation of the BLA was reduced in rats exposed to CUS, an effect that was inhibited by chronic antagonism of CRFR1. Furthermore, the reduction in BLA response to CRF was correlated with the anxiety trait of the animals, determined prior to initiation of the CUS. These results implicate CRFR1 in chronic stress-induced alterations in amygdala function and behavior. Furthermore, they show that CRFR1 antagonists can prevent changes induced by chronic stress, in particular in those animals that are highly anxious.