title: Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal.
abstract: OBJECTIVE
  Hypoglycemia is associated with a variety of adverse behaviors including fatigue, confusion and social withdrawal. While these clinical symptoms are well characterized, the mechanism of their cause is not understood. Here we investigated how insulin-induced hypoglycemia causes social withdrawal.
  
  
  METHODS
  Male 8-12-week-old C57BL/6J mice were injected intraperitoneally (IP) with or without and/or insulin, norepinephrine (NE) and epinephrine (Epi), terbutaline and butoxamine with subsequent measurement of blood glucose, social withdrawal and plasma catecholamines.
  
  
  RESULTS
  Insulin generated (0.75h post-injection) significant hypoglycemia with blood glucose nadirs of 64+/-4 and 48+/-5mg/dl for 0.8 and 1.2units/kg of insulin, respectively. Insulin (0.8 or 1.2units/kg) caused near total social withdrawal at 0.75h with full recovery not occurring until 4h (0.8units/kg) or 8h (1.2units/kg) post-insulin injection. Insulin also caused a marked elevation in plasma catecholamines. Basal 12h fasting NE and Epi were 287+/-38 and 350+/-47pg/ml, respectively. Insulin at 0.8units/kg increased plasma NE and Epi to 994+/-73 and 1842+/-473pg/ml, respectively. Administration of exogenous NE or Epi caused social withdrawal similar in magnitude to insulin. Importantly, administration of the beta-2 adrenergic receptor agonist terbutaline also caused social withdrawal while administration of the beta-2 adrenergic receptor antagonist butoxamine blocked NE-induced social withdrawal. Finally, butoxamine blocked insulin-induced social withdrawal.
  
  
  CONCLUSIONS
  These data demonstrate that hypoglycemia-associated social withdrawal is dependent on catecholamines via a beta-2 receptor-mediated pathway.
authors.affiliation: Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Guest
authors.forename: Meredith B
authors.initials: MB
authors.lastname: Barnes
authors.forename: Jonathan
authors.initials: J
authors.lastname: Martin
authors.forename: Uzma
authors.initials: U
authors.lastname: Ahmad
authors.forename: Jason M
authors.initials: JM
authors.lastname: York
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Freund
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002078:Butoxamine / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood / Q000494:pharmacology; D007003:Hypoglycemia / Q000139:chemically induced / Q000523:psychology*; D007004:Hypoglycemic Agents; D007328:Insulin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D012920:Social Behavior Disorders / Q000188:drug therapy* / Q000523:psychology*; D013726:Terbutaline / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D002078:Butoxamine; D013726:Terbutaline; D009638:Norepinephrine; D004837:Epinephrine