Blocking of beta-2 adrenergic receptors hastens recovery from hypoglycemia-associated social withdrawal

Min Jung Park, Christopher B. Guest, Meredith B. Barnes, Jonathan Martin, Uzma Ahmad, Jason M. York, Gregory G. Freund

    Research output: Contribution to journalArticlepeer-review


    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. Research design and 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 (0.75 h post-injection) significant hypoglycemia with blood glucose nadirs of 64 ± 4 and 48 ± 5 mg/dl for 0.8 and 1.2 units/kg of insulin, respectively. Insulin (0.8 or 1.2 units/kg) caused near total social withdrawal at 0.75 h with full recovery not occurring until 4 h (0.8 units/kg) or 8 h (1.2 units/kg) post-insulin injection. Insulin also caused a marked elevation in plasma catecholamines. Basal 12 h fasting NE and Epi were 287 ± 38 and 350 ± 47 pg/ml, respectively. Insulin at 0.8 units/kg increased plasma NE and Epi to 994 ± 73 and 1842 ± 473 pg/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.

    Original languageEnglish (US)
    Pages (from-to)1411-1418
    Number of pages8
    Issue number10
    StatePublished - Nov 2008


    • Beta-2 adrenergic receptor
    • Catecholamines
    • Hypoglycemia
    • Insulin treatment
    • Social withdrawal

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Endocrinology
    • Endocrine and Autonomic Systems
    • Psychiatry and Mental health
    • Biological Psychiatry


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