Du W, Harvey J A
Department of Pharmacology, MCP/Hahnemann School of Medicine, Allegheny University, Philadelphia, PA 19129, USA.
Brain Res. 1997 Jan 16;745(1-2):183-8. doi: 10.1016/s0006-8993(96)01148-1.
Harmaline is known to produce tremors and retard acquisition of the rabbit's nictitating membrane response. These actions have been demonstrated to depend on the ability of harmaline to activate the inferior olive which gives rise to climbing fibers that project directly onto Purkinje cells in cerebellar cortex. However, the precise receptor systems involved in harmaline's actions remains unknown. This study examined the role of the NMDA receptor in harmaline's actions. Harmaline (10 mg/kg, s.c.) produced intense tremors and impaired the acquisition of conditioned responses. Both of these effects of harmaline were significantly blocked by the prior administration of the noncompetitive NMDA channel blocker, dizocilpine (0.01 mg/kg, s.c. given 20 min prior to the administration of harmaline). This dose od dizocilpine had no effect on acquisition of conditioned responses when given alone. A higher dose of dizocilpine (0.1 mg/kg s.c.) completely blocked the tremorogenic effects of harmaline (10 mg/kg, s.c.). Dizocilpine had no effect on motor behavior when given alone. It was suggested that the blockade of harmaline's actions by dizocilpine may be occurring at NMDA channels within the inferior olive. Regardless of the site of action, these data demonstrate that harmaline's ability to activate the interior olivary nucleus depends on the normal activity of the NMDA receptor.
已知骆驼蓬碱会引发震颤，并延缓家兔瞬膜反应的习得。这些作用已被证明取决于骆驼蓬碱激活下橄榄核的能力，下橄榄核会产生攀爬纤维，这些纤维直接投射到小脑皮质的浦肯野细胞上。然而，骆驼蓬碱作用所涉及的确切受体系统仍不清楚。本研究考察了NMDA受体在骆驼蓬碱作用中的作用。骆驼蓬碱（10毫克/千克，皮下注射）引发强烈震颤，并损害条件反应的习得。在预先给予非竞争性NMDA通道阻滞剂地佐环平（0.01毫克/千克，在注射骆驼蓬碱前20分钟皮下注射）后，骆驼蓬碱的这两种作用均被显著阻断。单独给予该剂量的地佐环平对条件反应的习得没有影响。更高剂量的地佐环平（0.1毫克/千克，皮下注射）完全阻断了骆驼蓬碱（10毫克/千克，皮下注射）的致震颤作用。单独给予地佐环平时，它对运动行为没有影响。有人提出，地佐环平对骆驼蓬碱作用的阻断可能发生在下橄榄核内的NMDA通道处。无论作用部位如何，这些数据表明骆驼蓬碱激活下橄榄核的能力取决于NMDA受体的正常活性。
