The essential oil of bergamot enhances the levels of amino acid neurotransmitters in the hippocampus of rat: Implication of monoterpene hydrocarbons

The effects of bergamot essential oil (BEO) on the release of amino acid neurotransmitters in rat hippocampus have been studied by in vivo microdialysis and by in vitro superfusion of isolated nerve terminals. Intraperitoneal administration of BEO (100 μl/kg) significantly elevated the extracellular concentration of aspartate, glycine and taurine in a Ca2+-dependent manner. A dose-relation study generated a bell-shaped curve. When perfused into the hippocampus via the dialysis probe (20 μl/20 min), BEO produced a significant increase of extracellular aspartate, glycine, taurine as well as of GABA and glutamate. The augmentation of all amino acids was Ca2+-independent. Focally injected 1:1 diluted BEO preferentially caused extracellular increase of glutamate. Interestingly, this release appeared to be strictly Ca2+-dependent. BEO concentration-dependently enhanced the release of [3H]d-aspartate from superfused hippocampal synaptosomes. Similar results were obtained by monitoring the BEO-evoked release of endogenous glutamate. At relatively high concentrations, the BEO-induced [3H]d-aspartate release was almost entirely prevented by the glutamate transporter blocker dl-threo-β-benzyloxyaspartic acid (dl-TBOA) and was Ca2+-independent. At relatively low concentrations the release of [3H]d-aspartate was only in part (∼50%) dl-TBOA-sensitive and Ca2+-independent; the remaining portion of release was dependent on extracellular Ca2+. Interestingly, the monoterpene hydrocarbon-free fraction of the essential oil appeared to be inactive while the bergapten-free fraction superimposed the releasing effect of BEO supporting the deduction that psoralens may not be implicated. To conclude, BEO contains into its volatile fraction still unidentified monoterpene hydrocarbons able to stimulate glutamate release by transporter reversal and/or by exocytosis, depending on the dose administered.