title: 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.
abstract: BACKGROUND
  Chronic stress-induced depressive-like behavior is relevant to inflammatory immune activation. However, the neurobiological alterations in the brain following the central inflammatory immune activation remain elusive.
  
  
  METHODS
  Therefore, we investigated the neurobiological alterations during depressive-like behavior induced in mice by systemic administration of lipopolysaccharide (LPS; 1.2 mg/kg administered twice at a 30-min interval via intraperitoneal injection).
  
  
  RESULTS
  At 24 h after the second administration of LPS, an increased immobility time in the tail suspension test and the forced swimming test were observed, as well as reduced sucrose preference. Protein levels of the AMPA receptor GluR1 were significantly decreased at the plasma membrane in the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA), while levels of the GluR2 were increased at the plasma membrane in the nucleus accumbens (NAc) at 24h after LPS. However, total GluR1 and GluR2 protein levels in the mPFC, VTA, and NAc were not affected by LPS. Moreover, LPS facilitated release of noradrenaline in the mPFC and VTA, but not in the NAc. Consistently, systemic administration of prazosin, an α1-adrenoceptor antagonist, blocked the LPS-induced downregulation of the membrane GluR1 subunit in both the mPFC and VTA and also blocked the upregulation of the membrane GluR2 subunit in the NAc. Intracerebroventricular administration of prazosin 30 min before LPS injection abrogated the LPS-induced depressive-like behaviors. In opposition, administration of propranolol, a β-adrenoceptor antagonist, did not affect the LPS-induced downregulation of GluR1, the upregulation of GluR2, or the depressive-like behavior.
  
  
  CONCLUSIONS
  These results suggest that LPS-activated α1-adrenoceptor-induced downregulation of membrane GluR1 in the mPFC and VTA is associated with inflammation-induced depressive-like behavior.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan.
authors.forename: Miyu
authors.initials: M
authors.lastname: Sekio
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Ohu University, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611, Japan. k-seki@pha.ohu-u.ac.jp.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Seki
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003863:Depression / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000503:physiopathology; D011224:Prazosin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000503:physiopathology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D008070:Lipopolysaccharides; D009638:Norepinephrine; D011224:Prazosin; D043682:Receptor, Adenosine A1; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2
keywords: 1-adrenoceptor; depressive-like behavior; immune system; neuronal plasticity; reward system; α