Nectandra grandiflora essential oil and its isolated sesquiterpenoids minimize anxiety-related behaviors in mice through GABAergic mechanisms

Highlights: • N. grandiflora EO and its isolated compounds blunt anxiety-like behavior in mice. • EO and compounds induced anxiolytic-like effect without sedation. • GABAa receptors play a role in the EO and compounds anxiolytic-like effect. • Isolated compounds altered the synaptosomal membrane potential and calcium influx. • Calcium influx inhibition by compounds did not required GABAa receptors. -- Abstract: Nectandra grandiflora Ness (Lauraceae) essential oil (EO) main constituent, the sesquiterpenoid (+)-dehydrofukinone (DHF), has sedative and anticonvulsant effects through GABAergic mechanisms. Other DHF-related sesquiterpenoids have been identified in the EO, such as, dehydrofukinone epoxide (DFX), eremophil-11-en-10-ol (ERM) and selin-11-en-4-α-ol (SEL). However, the neuronal effects of these compounds in mammals remain unknown. Therefore, the aim of this study was to evaluate the anxiolytic potential of the N. grandiflora EO and the isolated compounds in in mice. For this purpose, mice were administered orally with vehicle, 10, 30 or 100 mg/kg EO, DHF, DFX, ERM or SEL or 1 mg/kg diazepam. Locomotion and ethological parameters in the open field (OF) and elevated plus maze (EPM) were recorded. We also examined the effect of DFX, ERM and SEL on the membrane potential and calcium influx in synaptosomes, and the presence of the compounds in the cortical tissue using gas chromatography. EOs and isolated compounds reduced anxiety-related parameters in the EPM (open arms time and entries, end activity, head dipping) and OF (center time and entries, total rearing, unprotected rearing, sniffing, grooming) without alter ambulation or induce sedation. Flumazenil (2 mg/kg, i.p.) altered the anxiolytic-like effect of all treatments and vanished the DFX, ERM and SEL-induced changes in membrane potential. However, FMZ did not blocked the DFX-, ERM- and SEL-induced inhibition of calcium influx. Therefore, our results suggest that N. grandiflora EO and isolated compounds induced anxiolytic-like effect in mice due to positive modulation of GABAa receptors and/or inhibition of neuronal calcium influx.