Acute isoproterenol induces anxiety-like behavior in rats and increases plasma content of extracellular vesicles

Physiol Behav. 2015 Apr 1;142:79-84. doi: 10.1016/j.physbeh.2015.02.002. Epub 2015 Feb 2.


Several clinical observations have demonstrated a link between heart rate and anxiety or panic disorders. In these patients, β-adrenergic receptor function was altered. This prompted us to investigate whether the β-adrenergic receptor agonist isoproterenol, at a dose that stimulates peripheral β-adrenergic system but has no effects at the central nervous system, can induce anxiety-like behavior in rats. Moreover, some possible messengers involved in the peripheral to brain communication were investigated. Our results showed that isoproterenol (5 mg kg(-1) i.p.) increased heart rate, evoked anxiety-like behavior, did not result in motor impairments and increased extracellular vesicle content in the blood. Plasma corticosterone level was unmodified as well as vesicular Hsp70 content. Vesicular miR-208 was also unmodified indicating a source of increased extracellular vesicles different from cardiomyocytes. We can hypothesize that peripheral extracellular vesicles might contribute to the β-adrenergic receptor-evoked anxiety-like behavior, acting as peripheral signals in modulating the mental state.

Keywords: Anxiety-like behavior; Extracellular vesicles; Hsp70; Isoproterenol; miR-208.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / blood
  • Anxiety / chemically induced*
  • Blood Chemical Analysis
  • Blotting, Western
  • Cardiovascular Agents / pharmacology*
  • Corticosterone / blood
  • Electrocardiography
  • Extracellular Vesicles / drug effects*
  • Extracellular Vesicles / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Heart Rate / drug effects
  • Isoproterenol / pharmacology*
  • Male
  • MicroRNAs / metabolism
  • Motor Activity / drug effects
  • Psychotropic Drugs / pharmacology*
  • Rats, Sprague-Dawley


  • Cardiovascular Agents
  • HSP70 Heat-Shock Proteins
  • MIRN208 microRNA, rat
  • MicroRNAs
  • Psychotropic Drugs
  • Isoproterenol
  • Corticosterone