Geraniol Enhances Inhibitory Inputs to Paraventricular Thalamic Nucleus and Induces Sedation in Mice

Abstract

Geraniol (GE), a plant-derived acyclic monoterpene, shows a wide variety of beneficial effects. Notably, recent studies have reported the potential sedative effects of GE in fish and rats. However, the mechanisms of GE in sedation remain elusive. Here, we found that GE reduced locomotion, relieved pentylenetetrazol (PTZ)-induced seizures, altered the electroencephalogram (EEG), and facilitated general anesthesia in mice. Meanwhile, GE decreased c-Fos expression and suppressed the calcium activity in the paraventricular thalamic nucleus (PVT). Microinjection of GE into the PVT reduced locomotion and facilitated propofol-induced anesthesia. Furthermore, the electrophysiology results showed that GE-induced dramatic membrane hyperpolarization and suppressed the neuronal activity of PVT neurons, mainly by prolonging spontaneous inhibitory postsynaptic currents and inducing tonic inhibitory currents via GABAA receptors. Our study revealed that GE enhances inhibitory inputs to PVT neurons and induces sedation in mice. These findings provide a potential candidate for further development of sedatives and anesthetics. Graphic Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/441289v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@fd8424org.highwire.dtl.DTLVardef@1ee77caorg.highwire.dtl.DTLVardef@faab42org.highwire.dtl.DTLVardef@101b921_HPS_FORMAT_FIGEXP M_FIG C_FIG