Lipopolysaccharide-Induced Depressive-Like Behavior is Associated with α1-Adrenoceptor Dependent Downregulation of the Membrane GluR1 Subunit in the Mouse Medial Prefrontal Cortex and Ventral Tegmental Area

• DOI: 10.1093/ijnp/pyu005
• Publication Date: 2015-05-26T17:08:05Z
• Authors: Miyu Sekio; Kenjiro Seki
• Keywords: 0301 basic medicine; 03 medical and health sciences; Research Article

Chronic stress-induced depressive-like behavior is relevant to inflammatory immune activation. However, the neurobiological alterations in brain following central activation remain elusive. Therefore, we investigated during induced mice by systemic administration of lipopolysaccharide (LPS; 1.2mg/kg administered twice at a 30-min interval via intraperitoneal injection). At 24h after second LPS, an increased immobility time tail suspension test and forced swimming were observed, as well reduced sucrose preference. Protein levels AMPA receptor GluR1 significantly decreased plasma membrane medial prefrontal cortex (mPFC) ventral tegmental area (VTA), while GluR2 nucleus accumbens (NAc) LPS. total protein mPFC, VTA, NAc not affected Moreover, LPS facilitated release noradrenaline mPFC but NAc. Consistently, prazosin, α1-adrenoceptor antagonist, blocked LPS-induced downregulation subunit both VTA also upregulation Intracerebroventricular prazosin 30min before injection abrogated behaviors. In opposition, propranolol, β-adrenoceptor did affect GluR1, GluR2, or behavior. These results suggest that LPS-activated α1-adrenoceptor-induced associated with inflammation-induced