Meeting Abstract

P2.138  Thursday, Jan. 5  Ginseng Derivative Ocotillol Enhances Neuronal Activity through Increased Glutamate Release: A Possible Mechanism Underlying Increased Spontaneous Locomotor Activity of Mice WANG, Z.-J.; SUN, L.; PENG, W.; MA, S.; ZHU, C.; FU, F.; HEINBOCKEL, T.*; Howard Univ. Coll. of Medicine, Washington, DC; Howard Univ. Coll. of Medicine, Washington, DC; Luye Pharma Group Ltd., Yantai, Shandong, China; Luye Pharma Group Ltd., Yantai, Shandong, China; Yantai Univ., Pharmacy, Yantai, Shandong, China; Yantai Univ., Pharmacy, Yantai, Shandong, China; Howard Univ. Coll. of Medicine, Washington, DC theinbockel@howard.edu

Ginsenosides are the main active ingredients in ginseng. Ocotillol is a derivate of pseudoginsenoside-F11, which is an ocotillol-type ginsenoside found in American ginseng. We examined the effects of ocotillol on neuronal activity of mitral cells (MC) in mouse olfactory bulb slices using whole-cell patch-clamp recording, and on animal behavior by measuring locomotor activity of mice. Ocotillol evoked action potential firing and membrane depolarization of MCs. In blockers of AMPA/kainate (CNQX), NMDA (D-AP5) and GABA-A (gabazine) receptors, the excitatory effect of ocotillol was abolished. The ocotillol effect persisted in gabazine but was eliminated by applying CNQX and D-AP5, suggesting that ionotropic glutamate receptors were involved in the effects of ocotillol. In voltage-clamp, ocotillol evoked an inward current and an increased frequency of spontaneous glutamatergic EPSCs. Both the inward current and sEPSCs were blocked by CNQX and D-AP5. Our results indicate that the excitatory action of ocotillol on MCs was mediated by enhanced glutamate release. Behavioral experiments demonstrated that ocotillol increased locomotor activity of mice. Our results suggest that ocotillol-evoked excitability was mediated by increased glutamate release, which may be responsible for the increased spontaneous locomotor activity. Support: Whitehall Foundation, U.S. PHS grants S06GM08016 (MBRS-SCORE, NIGMS/NIH), U54NS039407 (SNRP, NINDS/NIH), 2G12RR003048 (RCMI, NIH-NCRR).