Behavioral profiling of NPY in aggression and neuropsychiatric diseases

The abundantly expressed neuropeptide Y (NPY) has potent effects on feeding, body weight, and blood pressure, and exhibits important functions in various behavioral domains such as motor activity and anxiety. The potent neurotransmitter exerts its biological effects through at least five G-protein coupled receptors termed Y1, Y2, Y4, Y5, and y6. The behavioral profile of NPY function has been extensively studied using traditional pharmacological and classic genetic animal models. Based on these studies, variations in the profile of NPY and its receptors have been found. To limit the variability and inconsistencies in the behavioral profile of NPY and to clarify its effects on certain domains in further detail, it is important to design a rational standardized strategy for behavioral testing, using a complement of different well-established and reproducible tests. This strategy can minimize the risk that false positive or false negative results lead to a contradictory and inconsistent behavioral characterization of NPY function. Ideally, such screening should be composed of an initial monitoring of general health, sensory functions, and motor abilities, before specific behavioral domains such as anxiety or aggression are investigated using a multi-tiered phenotyping approach. In this review, we will focus on a brief description of the latest insights into the behavioral profile of NPY in the selective lesser investigated domains such as aggression and depression–schizophrenia-related behaviors. We will combine this information with possible strategies to evaluate the different specific phenotypes in more detail.