RT Journal A1 Tasan, Ramon O. A1 Nguyen, Ngoc Khoi A1 Weger, Stefan A1 Sartori, Simone B. A1 Singewald, Nicolas A1 Heilbronn, Regine A1 Herzog, Herbert A1 Sperk, Günther T1 The Central and Basolateral Amygdala Are Critical Sites of Neuropeptide Y/Y2 Receptor-Mediated Regulation of Anxiety and Depression JF The Journal of Neuroscience JO The Journal of Neuroscience YR 2010 FD May 05 VO 30 IS 18 SP 6282 OP 6290 DO 10.1523/JNEUROSCI.0430-10.2010 UL http://www.jneurosci.org/content/30/18/6282.abstract AB Anxiety is integrated in the amygdaloid nuclei and involves the interplay of the amygdala and various other areas of the brain. Neuropeptides play a critical role in regulating this process. Neuropeptide Y (NPY), a 36 aa peptide, is highly expressed in the amygdala. It exerts potent anxiolytic effects through cognate postsynaptic Y1 receptors, but augments anxiety through presynaptic Y2 receptors. To identify the precise anatomical site(s) of Y2-mediated anxiogenic action, we investigated the effect of site-specific deletion of the Y2 gene in amygdaloid nuclei on anxiety and depression-related behaviors in mice. Ablating the Y2 gene in the basolateral and central amygdala resulted in an anxiolytic phenotype, whereas deletion in the medial amygdala or in the bed nucleus of the stria terminalis had no obvious effect on emotion-related behavior. Deleting the Y2 receptor gene in the central amygdala, but not in any other amygdaloid nucleus, resulted in an added antidepressant-like effect. It was associated with a reduction of presumably presynaptic Y2 receptors in the stria terminalis/bed nucleus of the stria terminalis, the nucleus accumbens, and the locus ceruleus. Our results are evidence of the highly site-specific nature of the Y2-mediated function of NPY in the modulation of anxiety- and depression-related behavior. The activity of NPY is likely mediated by the presynaptic inhibition of GABA and/or NPY release from interneurons and/or efferent projection neurons of the basolateral and central amygdala.