Abstract
Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We previously showed that intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC) and localized these effects to the dorsolateral septum (DLS) and central amygdala (CeA). In the present study, we aimed to identify the receptor subtypes that mediate these local effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduced the expression of SFC-induced social fear in a brain region- and receptor-specific manner in male mice. In the DLS, NPY reduced the expression of social fear by acting on Y2 receptors but not on Y1 receptors. As such, prior administration of the Y2 receptor antagonist BIIE0246 (0.2 nmol/0.2 μL/side) but not the Y1 receptor antagonist BIBO3304 trifluoroacetate (0.2 nmol/0.2 μL/side) blocked the effects of NPY in the DLS. In the CeA, however, BIBO3304 trifluoroacetate but not BIIE0246 blocked the effects of NPY, suggesting that NPY reduced the expression of social fear by acting on Y1 receptors but not Y2 receptors within the CeA. This study suggests that at least two distinct receptor subtypes are differentially recruited in the DLS and CeA to mediate the effects of NPY on the expression of social fear.
Highlights
As the most abundant and widely distributed neuropeptide in the mammalian brain, neuropeptide Y (NPY) regulates a variety of biological and pathophysiological functions, such as blood pressure, food intake, neuroendocrine secretions, neuronal excitability and neuroplasticity [1,2,3,4,5,6]
In a model of social fear conditioning (SFC), we showed that i.c.v. administration of NPY reduced the expression of social fear by simultaneously acting on Y1 and Y2 receptors [36]
The present study demonstrates for the first time that NPY reduces the expression of SFC-induced social fear in a brain region-and receptor-specific manner in male mice
Summary
As the most abundant and widely distributed neuropeptide in the mammalian brain, neuropeptide Y (NPY) regulates a variety of biological and pathophysiological functions, such as blood pressure, food intake, neuroendocrine secretions, neuronal excitability and neuroplasticity [1,2,3,4,5,6] These effects are mediated by at least five subtypes of G-protein-coupled receptors, among which the Y1, Y2, Y4 and Y5 subtypes are localized in the brain [7,8,9]. The anxiolytic-like effects observed after i.c.v. or after local administration of NPY into the CeA, lateral septum and CA1 region of the hippocampus are mediated by postsynaptic Y1 receptors [14,17,18,21], whereas the intra-dentate gyrus effects are mediated by presynaptic Y2 receptors [18] These studies suggest a brain region- and receptor-specific modulation of anxiety-like behavior by NPY. While postsynaptic Y1 receptors were shown to mediate primarily anxiolytic-like effects [14,17,18,21], the activation of presynaptic Y2 receptors exerts predominantly anxiogenic-like effects, as demonstrated in studies using specific Y2 receptor agonists and antagonists [22,23]
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