Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat
Evidences of cannabinoids-induced modulation of paroxysmal events in an experimental model of partial epilepsy in the rat
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DOI：
10.1016/j.neulet.2009.07.014
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发表时间：
2009-09-22
影响因子：
2.5
通讯作者：
Sardo, Pierangelo
中科院分区：
文献类型：
--
作者：
Rizzo, Valerio;Ferraro, Giuseppe;Sardo, Pierangelo
大麻素（CB）的抗惊厥作用已被证明是由CB1受体的激活介导的。本研究评价了（R）-（+）-[2，3-二氢-5-甲基-3-（三氟甲基）苯基]-N-甲基-N-（三氟甲基）-N-甲基-N-（三氟甲基）苯基]-N-甲基-N-（三氟甲基）-N-甲基-N-（三氟甲基）-N-甲基-N-（三氟甲基）苯基]-N-甲基-N-（三氟甲基）-N-甲基-N-（三氟甲基）-N-甲基-N-（三氟甲基）-N-甲基-N-（三氟甲基）-N-（三氟甲基）-N-甲基-N-（三氟甲基）-N-甲基-N-（三氟甲基）-N-甲基-N-N-（三氟甲基）-N-甲基-N-N-（三氟甲基）-N-（三氟甲基）-N-甲基-N-N-（三氟甲基）-N-（三氟甲基）-N-甲基-N-N-（三氟甲基）-（4-吗啉基甲基）吡咯并[1，2，3-de]-1，4-苯并恶嗪-6-基]-1-萘甲酮（WIN55，212 - 2，CB激动剂）单独或在施用N-（哌啶-1-基）-5-（4-碘苯基）-1-（2，4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺（AM 251，选择性CB 1拮抗剂）在大鼠复杂部分性癫痫发作（最大齿状回激活-MDA）的实验性体内模型中的作用。WIN55，212 - 2（21 mg kg（-1））具有抗惊厥作用，但AM 251（1 mg kg（-1），间隔30 min）预处理可显著降低其作用。令人惊讶的是，以相同剂量单独施用的AM 251未能诱导MDA应答的任何改变。我们的数据表明，参与CB系统的抑制控制过度兴奋现象的急性部分性癫痫模型。尽管MDA模型本身不诱导CB 1受体的基础活化，如AM 251单独给药时缺乏效力所表明的，但在用AM 251预处理的大鼠中对WIN55，212 - 2诱导的作用的部分抑制允许假设WIN55，212 - 2诱导的作用是由AM 251单独给药引起的。212 - 2诱导的抗癫痫作用与CB1受体活化增加或与其他受体亚型的参与密切相关。(c)2009爱思唯尔爱尔兰有限公司保留所有权利。
The anticonvulsant effect of cannabinoids (CB) has been shown to be mediated by the activation of the CB1 receptor. This study evaluates the anticonvulsant activity of (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-Yl]-1-naphthalenylmethanone (WIN55,212-2, CB agonist) alone or preceded by the administration of N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, selective CB1 antagonist) in an experimental in vivo model of complex partial seizures (maximal dentate gyrus activation - MDA) in the rat. WIN55,212-2 (21 mg kg(-1)) exerted an anticonvulsant effect, significantly reduced by the pretreatment with AM251 (1 mg kg(-1), 30 min interval). Surprisingly, AM251, administered alone at the same dose, failed to induce any modification in MDA responses. Our data suggest the involvement of the CB system in the inhibitory control of hyperexcitability phenomena in a model of acute partial epilepsy. Although the MDA model per se does not induce a basal activation of CB1 receptors, as suggested by the lack of efficacy of AM251 when administered alone, the partial suppression of WIN55,212-2-induced effects in rats pre-treated with AM251 allows to hypothesise that the WIN55,212-2-induced antiepileptic effect is strictly linked to an increased CB1 receptor activation or to the involvement of further receptor subtypes. (c) 2009 Elsevier Ireland Ltd. All rights reserved.