Tanaka Ken-ichi, Yagi Takao, Shimakoshi Ryosuke, Azuma Koji, Nanba Takeshi, Ogo Hiroya, Tamura Akiko, Asanuma Masato
Department of Clinical Pharmacy, Shujitsu University School of Pharmacy, Okayama, Japan.
Neurosci Lett. 2009 Oct 25;462(3):235-8. doi: 10.1016/j.neulet.2009.07.024. Epub 2009 Jul 15.
Nitric oxide (NO) may play a role in the established processes of learning and memory. We examined the effects of N(omega)-nitro-L-arginine methylester (L-NAME), a nonselective inhibitor of NO synthase (NOS), on the performance of mice in a Y-maze task. L-NAME (100 mg/kg) markedly impaired spontaneous alternation behavior. However, galantamine (0.5 mg/kg) significantly attenuated this l-NAME-induced impairment. To clarify the molecular basis underlying galantamine's protective effects against L-NAME-induced impairment of spontaneous alternation behavior, we tested the ability of mecamylamine, an antagonist of nicotinic ACh receptor (nAChR), and scopolamine, an antagonist of muscarinic ACh receptor, to reduce galantamine's protective effects, and found that only the former had such an ability. Galantamine significantly also reduced L-NAME-induced decreases in NOx levels. However, mecamylamine cancelled galantamine's efficacy in countering the L-NAME-induced decrease in NOx levels. In the present study, we have determined that galantamine's protection against L-NAME-induced impairment of spontaneous alternation behavior in the Y-maze task might be mediated mainly by NOergic activation via the nAChR-related pathway.
一氧化氮（NO）可能在已确立的学习和记忆过程中发挥作用。我们研究了一氧化氮合酶（NOS）的非选择性抑制剂N（ω）-硝基-L-精氨酸甲酯（L-NAME）对小鼠在Y迷宫任务中表现的影响。L-NAME（100毫克/千克）显著损害自发交替行为。然而，加兰他敏（0.5毫克/千克）显著减轻了这种L-NAME诱导的损害。为了阐明加兰他敏对L-NAME诱导的自发交替行为损害的保护作用的分子基础，我们测试了烟碱型乙酰胆碱受体（nAChR）拮抗剂美加明和毒蕈碱型乙酰胆碱受体拮抗剂东莨菪碱降低加兰他敏保护作用的能力，发现只有前者有这种能力。加兰他敏还显著降低了L-NAME诱导的NOx水平下降。然而，美加明消除了加兰他敏对抗L-NAME诱导的NOx水平下降的功效。在本研究中，我们确定加兰他敏对Y迷宫任务中L-NAME诱导的自发交替行为损害的保护作用可能主要通过与nAChR相关的途径由NO能激活介导。
