Epileptiform activity in the CA1 region of the hippocampus becomes refractory to attenuation by cannabinoids in part because of endogenous γ-aminobutyric acid type B receptor activity.
Epileptiform activity in the CA1 region of the hippocampus becomes refractory to attenuation by cannabinoids in part because of endogenous γ-aminobutyric acid type B receptor activity.
复制标题
海马 CA1 区的癫痫样活性变得难以被大麻素减弱，部分原因是内源性 γ-氨基丁酸 B 型受体活性。
DOI：
10.1002/jnr.23027
复制
发表时间：
2012
影响因子：
4.2
通讯作者：
Levine,EricS
中科院分区：
文献类型：
--
作者：
Messer,RickaD;Levine,EricS
几个世纪以来，大麻的抗惊厥特性已为人所知。因此，最近表征的内源性大麻素系统代表了新型抗惊厥药物的一个有希望的目标；然而，外源性大麻素的施用在人类癫痫和动物模型中显示出不同的结果。大麻素减弱兴奋性和抑制性神经递质释放的能力可能解释了大麻素在不同癫痫模型中的不同作用，但这一点尚未得到很好的探索。使用急性小鼠脑切片，我们监测了海马 CA1 区域的场电位，以系统地表征大麻素激动剂 WIN55212-2 (WIN) 对诱发基础和癫痫样活动的影响。 WIN作用于突触前，显着降低了基底场兴奋性突触后电位的幅度和斜率，以及由于细胞外溶液中镁的缺失而引起的刺激诱发的癫痫样反应。相比之下，镁的缺失加上钾的升高相结合会诱发癫痫样反应，而这种反应对于 WIN 的减弱是难以控制的。通过阻断 B 型 γ-氨基丁酸 (GABAB) 受体，WIN 在该模型中的作用部分恢复，但 GABAA 受体未阻断。癫痫样活动模型的细微差异可以深刻地改变大麻素的功效。内源性 GABAB 受体激活在大麻素敏感性降低中发挥了作用，该敏感性降低是由镁缺失和钾升高引起的癫痫样活动引起的。这些结果表明，突触前 G 蛋白偶联受体与重叠下游靶点之间的相互作用可能是大麻素在不同癫痫模型中不同功效的基础。 © 2012 Wiley 期刊公司。
The anticonvulsant properties of marijuana have been known for centuries. The recently characterized endogenous cannabinoid system thus represents a promising target for novel anticonvulsant agents; however, administration of exogenous cannabinoids has shown mixed results in both human epilepsy and animal models. The ability of cannabinoids to attenuate release of both excitatory and inhibitory neurotransmitters may explain the variable effects of cannabinoids in different models of epilepsy, but this has not been well explored. Using acute mouse brain slices, we monitored field potentials in the CA1 region of the hippocampus to characterize systematically the effects of the cannabinoid agonist WIN55212‐2 (WIN) on evoked basal and epileptiform activity. WIN, acting presynaptically, significantly reduced the amplitude and slope of basal field excitatory postsynaptic potentials as well as stimulus‐evoked epileptiform responses induced by omission of magnesium from the extracellular solution. In contrast, the combination of omission of magnesium plus elevation of potassium induced an epileptiform response that was refractory to attenuation by WIN. The effect of WIN in this model was partially restored by blocking γ‐aminobutyric acid type B (GABAB), but not GABAA, receptors. Subtle differences in models of epileptiform activity can profoundly alter the efficacy of cannabinoids. Endogenous GABABreceptor activation played a role in the decreased cannabinoid sensitivity observed for epileptiform activity induced by omission of magnesium plus elevation of potassium. These results suggest that interplay between presynaptic G protein‐coupled receptors with overlapping downstream targets may underlie the variable efficacy of cannabinoids in different models of epilepsy. © 2012 Wiley Periodicals, Inc.