GINSENG DERIVATIVE OCOTILLOL ENHANCES NEURONAL ACTIVITY THROUGH INCREASED GLUTAMATE RELEASE: A POSSIBLE MECHANISM UNDERLYING INCREASED SPONTANEOUS LOCOMOTOR ACTIVITY OF MICE

摘要

Ginsenosides are the main active ingredients in ginseng and have recently been reported to have beneficial effects on the CNS. Ocotillol is a derivate of pseudoginsen-oside-F11, which is an ocotillol-type ginsenoside found in American ginseng. We examined the effects of ocotillol (a) on neuronal activity of projection neurons, mitral cells (MC), in a mouse olfactory bulb brain slice preparation using whole-cell patch-clamp recording, and (b) on animal behavior by measuring locomotor activity of mice in vivo. Ocotillol displayed an excitatory effect on spontaneous action potential firing and depolarized the membrane potential of MCs. The effect was concentration-dependent, with an EC_50 of 4 muM. In the presence of blockers of ionotropic glutamatergic and GABAergic synaptic transmission (6-cyano-7-nitroquinoxa-line-2,3-dione [CNQX], 10 muM; D-AP5, 50 muM; gabazine, 5 muM), the excitatory effect of ocotillol on firing was abolished. Further experiments showed that the ocotillol-induced neuronal excitation persisted in the presence of GABA_A receptor antagonist gabazine but was eliminated by applying AM PA/ kainate receptor antagonist CNQX and W-methyl-D-aspartate (NMDA) receptor antagonist D-AP5, suggesting that ionotropic glutamate transmission was involved in mediating the effects of ocotillol. Bath application of ocotillol evoked an inward current as well as an increased frequency of spontaneous glutamatergic excitatory postsynaptic currents (EPSCs). Both the inward current and sEPSCs could be blocked by ionotropic glutamate receptor antagonists CNQX and D-AP5. These results indicate that the excitatory action of ocotillol on MCs was mediated by enhanced glutamate release. Behavioral experiments demonstrated that ocotillol increased locomotor activities of mice. Our results suggest that ocotillol-evoked neuronal excitability was mediated by increased release of glutamate, which may be responsible for the increased spontaneous locomotor activities in vivo.