Methyleugenol Potentiates Central Amygdala GABAergic Inhibition and Reduces Anxiety

The central amygdala (CeA) plays a critical role in the expression of emotional behaviors, including pathologic anxiety disorders. The present study demonstrated that GABAergic inhibition in CeA was significantly increased by methyleugenol (ME), a natural constituent isolated from the essential oils of several plants. The electrophysiologic recordings showed that ME increased both tonic and miniature inhibitory postsynaptic GABAergic currents in CeA slices, especially the tonic currents, while the miniature excitatory postsynaptic currents were not affected. In the fear-induced anxiety animal model, both intraperitoneal injection or CeA-specific infusion of ME reduced the anxiety-like behaviors in mice, likely by facilitating the activation of A-type GABA receptors (GABA_ARs). These results reveal that GABA_AR in the CeA can be a potential therapeutic target for the treatment of anxiety and that ME is capable of enhancing the GABAergic inhibition in CeA neurons for the inhibition of neuronal excitability.