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.