Experiments to localize the site for the anxiogenic action of NPY mediated by Y₂ receptors in the mouse brain

Neuropeptide Y (NPY) is abundant in the nervous system. It acts through Y₁, Y₂, Y₄ and Y₅ receptors and is involved in a variety of brain functions. When applied locally into the amygdala, NPY exerts an anxiolytic action, presumably mediated by Y₁ receptors. Depletion of Y₂ receptors induces an anxiolytic phenotype, possibly by abolishing the release-inhibiting action of presynaptic Y₂ receptors. In the present study we aimed to find the exact site of the presumed anxiogenic action mediated by Y₂ receptors. We conducted site-specific deletions of Y₂ receptors in Y₂^lox/lox mice by local injection of an AAV-Cre vector into the hippocampus and the amygdala. As controls, an AAV-GFP vector was injected in Y₂^lox/lox littermates at the same sites. Expression of Cre and GFP was verified by in situ hybridization and immunohistochemistry. Deletion of Y₂ receptors was visualized by receptor autoradiography and in situ hybridization. After bilateral injection of an AAV-Cre vector into the basolateral amygdala, mice revealed a tendency towards an anxiolytic phenotype in the light-dark test (LDT). When deletion of Y₂ receptors was confined to the central nucleus of the amygdala, an anxiolytic phenotype was observed in the elevated plus maze and the LDT. Moreover, a better stress coping ability was demonstrated in the tail suspension test. In contrast, no anxiolytic effect was detected after intrahippocampal injections. The experiments indicate that the anxiolytic and antidepressant-like effects of Y₂ receptor deletion may be generated in certain subnuclei of the amygdala.