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

•Isoproterenol (5 mg kg− 1) increases HR and induces anxiety-like behavior in rats.•The same treatment increases blood content of extracellular vesicles (EVs).•Stress markers (corticosterone and EV Hsp70 content) are not modified.•Peripheral signals via EVs can reach the CNS and modulate anxiety.

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.