Bausch S B, Esteb T M, Terman G W, Chavkin C
Department of Pharmacology, University of Washington, Seattle, USA.
J Pharmacol Exp Ther. 1998 Mar;284(3):1147-55.
The effects of kappa opioids on seizures and seizure-induced histopathology were investigated with the pilocarpine model of temporal lobe epilepsy. Rats treated with the kappa opioid receptor agonist U50488h before pilocarpine showed: 1) increased seizure latency; 2) decreased seizure duration; 3) decreased mossy fiber sprouting; and 4) increased hilar neuron survival when compared with rats pretreated with saline. Behavioral effects of U50488h were blocked by the kappa opioid receptor antagonist norbinaltorphimine (nBNI), whereas the changes caused by U50488h in the histological response to pilocarpine were not blocked by nBNI. Rats treated with nBNI before pilocarpine exhibited: 1) increased incidence of seizures; 2) increased mossy fiber sprouting; and 3) increased hilar neuron loss when compared with rats treated with pilocarpine alone. These changes suggest a protective role of endogenously released kappa opioids in this seizure model. The location of functional kappa opioid receptors in the rat dentate gyrus was documented electrophysiologically to enable correlation with kappa opioid effects on histopathology. The kappa selective agonist, U69593, reversibly decreased the amplitude of excitatory postsynaptic potentials in the middle molecular layer of the dentate gyrus from the ventral but not the more dorsal portion of the hippocampal formation. Thus, kappa opioids decreased the severity and incidence of behavioral seizures and secondarily decreased seizure-induced histopathology via the decreased incidence of seizures.
采用毛果芸香碱颞叶癫痫模型研究了κ阿片类物质对癫痫发作及癫痫发作诱导的组织病理学的影响。在给予毛果芸香碱之前用κ阿片受体激动剂U50488h处理的大鼠表现为：1）癫痫发作潜伏期延长；2）癫痫发作持续时间缩短；3）苔藓纤维出芽减少；4）与用生理盐水预处理的大鼠相比，门区神经元存活率增加。U50488h的行为学效应被κ阿片受体拮抗剂纳洛酮肟（nBNI）阻断，而U50488h引起的对毛果芸香碱组织学反应的变化未被nBNI阻断。在给予毛果芸香碱之前用nBNI处理的大鼠表现为：1）癫痫发作发生率增加；2）苔藓纤维出芽增加；3）与单独用毛果芸香碱处理的大鼠相比，门区神经元丢失增加。这些变化表明内源性释放的κ阿片类物质在该癫痫模型中具有保护作用。通过电生理学记录了大鼠齿状回中功能性κ阿片受体的位置，以便与κ阿片类物质对组织病理学的影响相关联。κ选择性激动剂U69593可逆性降低了海马结构腹侧而非背侧部分齿状回中层分子兴奋性突触后电位的幅度。因此，κ阿片类物质降低了行为性癫痫发作的严重程度和发生率，并继发于癫痫发作发生率的降低而减少了癫痫发作诱导的组织病理学变化。
