Regulation of Anxiety‐like Behavior by Neuropeptide Y and Corticotropin Releasing Factor

Abstract

Anxiety is an emotional response that may lead to many psychiatric disorders. The basolateral nucleus of the amygdala (BLA) is an important brain region for the regulation of the physiological and behavioral responses to stressors and appears to play an important role in the etiology of anxiety and panic disorder. Our laboratories have sought to understand the role of NPY and CRF in the BLA. We explored the actions of NPY and NPY analogs administered bilaterally into the BLA on anxiety-like behavior as assessed using the social interaction (SI) test. NPY and NPY analogs appear to produce anxiolytic-like effects via the Y1 and Y5 receptors while activation of the Y2 receptor produces anxiogenic-like effects. On the other hand, CRF and the related peptide, Urocortin, produce anxiogenic-like actions via the CRF1 receptor. In subsequent studies, we found that 3 day repeated “sub-threshold” administration of Ucn into the BLA results in a behavioral sensitivity to lactate in treated rats. Continued treatment of the rats for 5 days produced a persistent anxiety state that was observed for an additional 5 weeks without Ucn administration. Electrophysiological studies on the BLA of these animals suggest a profound loss of inhibitory input resulting in increased excitability. Therefore, the NPY and CRF systems play an important role in BLA excitability and may have an important role in the etiology of anxiety and panic disorder.