Brain Region-Dependent Effects of Neuropeptide Y on Conditioned Social Fear and Anxiety-Like Behavior in Male Mice.

Johannes Kornhuber,Iulia Zoicas

doi:10.3390/ijms22073695

Johannes Kornhuber, Iulia Zoicas

Open Access

https://doi.org/10.3390/ijms22073695

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Abstract

Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that the intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC). In the present study, we aimed to identify the brain regions that mediate these effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduces the expression of SFC-induced social fear in a brain-region-dependent manner. In more detail, NPY reduced the expression of social fear when administered into the dorsolateral septum (DLS) and central amygdala (CeA), but not when administered into the dorsal hippocampus (DH), medial amygdala (MeA) and basolateral amygdala (BLA). We also investigated whether the reduced expression of social fear might partly be due to a reduced anxiety-like behavior, and showed that NPY exerted anxiolytic-like effects when administered into the DH, DLS, CeA and BLA, but not when administered into the MeA. This study identifies the DLS and the CeA as brain regions mediating the effects of NPY on the expression of social fear and suggests that partly distinct neural circuitries mediate the effects of NPY on the expression of social fear and on anxiety-like behavior.

Highlights

Neuropeptide Y (NPY) is the most abundant and widely distributed neuropeptide in the mammalian brain
NPY promotes social interaction when administered into the dorsolateral septum (DLS) [23] and basolateral amygdala (BLA) [24], but does not affect social interaction when administered into the intramedial septum [23] and central amygdala (CeA) [24]
To investigate whether NPY alters the expression of social fear when administered into the dorsal hippocampus (DH), DLS, CeA, medial amygdala (MeA) and/or BLA, separate groups of conditioned (SFC+) and unconditioned (SFC−) mice were administered either vehicle (Veh; 0.2 μL/side) or NPY (0.1 nmol/0.2 μL/side) into these brain regions 10 min before social fear extinction on day 2

Summary

Introduction

Neuropeptide Y (NPY) is the most abundant and widely distributed neuropeptide in the mammalian brain It regulates important biological and pathophysiological functions, such as blood pressure, food intake, neuroendocrine secretions, seizures, neuronal excitability and neuroplasticity [1,2,3,4,5,6]. NPY promotes social interaction when administered into the dorsolateral septum (DLS) [23] and basolateral amygdala (BLA) [24], but does not affect social interaction when administered into the intramedial septum [23] and CeA [24] These anxiolytic and prosocial effects of NPY suggest its potential benefit in disorders associated with social anxiety and fear. Little is known about the involvement of NPY in the modulation of fear responses after adverse social events or about the neural circuitries mediating these effects

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