Involvement of nitrergic system in the anticonvulsant effect of the cannabinoid CB1 agonist ACEA in the pentylenetetrazole-induced seizure in mice
Involvement of nitrergic system in the anticonvulsant effect of the cannabinoid CB1 agonist ACEA in the pentylenetetrazole-induced seizure in mice
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DOI：
10.1016/j.eplepsyres.2009.01.003
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发表时间：
2009-04-01
影响因子：
2.2
通讯作者：
Dehpour, Ahmad Reza
中科院分区：
文献类型：
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作者：
Bahremand, Arash;Nasrabady, Sara Ebrahimi;Dehpour, Ahmad Reza
大麻素系统在癫痫阈值调节中发挥着关键作用，癫痫阈值调节主要通过大麻素 CB 受体的激活来介导。还有一些证据表明大麻素系统与其他神经递质（包括一氧化氮（NO）系统）之间存在相互作用。使用戊四唑 (PTZ) 诱导的 NMRI 小鼠阵挛性癫痫模型，我们研究了 NO 是否参与了大麻素对癫痫阈值的影响。注射选择性大麻素 CB、激动剂 ACEA（2 mg/kg，腹腔注射）显着 (P < 0.01) 增加了癫痫阈值，而用选择性 CB、拮抗剂 AM251 预处理可预防 (P < 0.001) 癫痫阈值。 （1 毫克/千克，腹腔注射）。 NO 前体 L-精氨酸（50 和 100 mg/kg，腹腔注射）增强了次有效剂量的 ACEA（1 mg/kg，腹腔注射）的抗惊厥作用。用无效剂量的非特异性 NOS 抑制剂 L-NAME（15 和 30 mg/kg，腹腔注射）和特异性神经元 NOS 抑制剂 7-NI（40 和 80 mg/kg，腹腔注射）而非诱导型 NOS 抑制剂氨基胍（10、50 和 100 mg/kg，腹腔注射）进行预处理，可阻止 ACEA（2 mg/kg，腹腔注射）的抗惊厥作用。 i.p.）。无效剂量的 AM251 (0.5 mg/kg) 与低剂量和本身无效剂量的 L-NAME (1 mg/kg, i.p.) 和 7-NI (10 mg/kg, i.p.) 共同给药对预防 ACEA (2 mg/kg, i.p.) 的抗惊厥作用具有显着 (P < 0.01) 作用。我们的研究结果表明，中枢 NO 系统可能参与特定大麻素 CB（激动剂 ACEA）的抗惊厥特性，强调癫痫调节中两个系统之间的相互作用。 (C) 2009 Elsevier B.V. 保留所有权利。
Cannabinoid system plays a pivotal rote in the seizure threshold modulation which is mainly mediated through activation of the cannabinoid CB, receptor. There is also several evidence of interaction between cannabinoid system and other neurotransmitters including nitric oxide (NO) system. Using model of clonic seizure induced by pentylenetetrazole (PTZ) in mate NMRI mice, we investigated whether NO is involved in the effects of cannabinoids on the seizure threshold.Injection of the selective cannabinoid CB, agonist ACEA (2 mg/kg, i.p.) significantly (P < 0.01) increased the seizure threshold which was prevented (P < 0.001) by pretreatment with the selective CB, antagonist AM251 (1 mg/kg, i.p.). The NO precursor L-arginine (50 and 100 mg/kg, i.p.) potentiated the anticonvulsant effects of the sub-effective dose of ACEA (1 mg/kg, i.p.). Pretreatment with non-effective doses of the non-specific NOS inhibitor L-NAME (15 and 30 mg/kg, i.p.) and the specific neuronal NOS inhibitor 7-NI (40 and 80 mg/kg, i.p.) but not the inducible NOS inhibitor aminoguanidine (10, 50 and 100 mg/kg, i.p.) prevented the anticonvulsant effect of ACEA (2 mg/kg, i.p.). Co-administration of non-effective dose of AM251 (0.5 mg/kg) with both low and per se non-effective doses of L-NAME (1 mg/kg, i.p.) and 7-NI (10 mg/kg, i.p.) had significant (P < 0.01) effect in preventing the anticonvulsant effect of ACEA (2 mg/kg, i.p.).Our findings demonstrated that central NO system could be involved in the anticonvulsant properties of the specific cannabinoid CB, agonist ACEA, emphasizing on the interaction between two systems in the seizure modulation. (C) 2009 Elsevier B.V. All rights reserved.