Interactions Between NPY and CRF in the Amygdala to Regulate Emotionality

Neuropeptide Y (NPY) is one of the most abundant peptides in the central nervous system and currently there are four known receptor subtypes Y1, Y2, Y4 and Y5. Central NPY and its receptors have been implicated in a variety of physiological processes such as epilepsy, sleep, obesity, learning and memory, gastrointestinal regulation, alcoholism, depression and anxiety. The localization of these receptors within the brain is consistent with the roles mentioned, as they are found in varying density within the limbic structures, such as the hippocampal formation, amygdala, hypothalamus and septum. It is well understood that NPY produces anxiolytic responses following central administration under stressful or anxiety-provoking situations. In contrast, central administration of the neuropeptide corticotropin-releasing factor (CRF) produces anxiogenic behaviors. It has been proposed that NPY counteracts the effects of CRF to maintain no net change in emotional state, e.g., emotional homeostasis. In this article, we review the scientific literature describing the NPY-CRF relationship, specifically as it relates to the modulation of the CRF-mediated stress responses via the amygdala, a key forebrain structure involved in the regulation of emotional states.