Brain neuropeptide Y (NPY) system: a candidate target for treatment of anxiety, depression and alcohol dependence

Abstract

Neuropeptide γ (NPY), the prototypical member of the NPY-like peptide family, antagonizes behavioral consequences of stress through actions within the brain. Behavioral antistress actions of NPY are noteworthy in that their magnitude surpasses that of other endogenous compounds, and they are produced across a wide range of animal models, nomally thought to reflect different aspects of emolionality. These findings suggest that NPY acts with a high potency on a common core mechanism of emotionality and behavioral stress responses. Behavioral studies in genetically modified animals support this hypothesis. Increased emotionality and increased alcohol intake is seen upon inactivation of NPY transmission, while the opposite is found when NPY signaling is made overactive. Together, available data point to the potential of the NPY system as a target for novel pharmacological treatments of stress-related disorders, including anxiely and depression. Recent data additionally point to a role of NPY in the regulation of alcohol intake, and alcohol dependence emerges as a novel potential indication for compounds targeting the NPY system.