Anxiety-Like Behaviors and Neuropeptide Y, Tachykinins and Beyond

Anxiety disorders affect a large number of individuals causing a heavy disease burden. Among peptide neurotransmitters, Neuropeptide Y (NPY) and tachykinin circuits are implicated in the pathophysiological basis of anxiety disorders and may represent therapeutic targets. NPY is expressed in anxiety-relevant brain regions and is modulated by anxiety-inducing stress exposures. In several animal models, NPY administration induces an anxiolytic profile mediated by Y1, Y2, and Y5 receptors. Intranasal NPY administration reduced anxiety in post-traumatic stress disorder patients, further supporting its role in modulating stress responses. Tachykinins include Substance P, Neurokinin A, and Neurokinin B, which are highly expressed in anxiety-mediating brain areas and bind with different affinities to three receptors: NK1, NK2, and NK3. In preclinical investigations, tachykinins showed anxiogenic activities, which can be reversed by NK1 and NK2 antagonists. Further research is needed to exploit the therapeutic potential of neuropeptidergic systems.