Becker A, Braun H, Schröder H, Grecksch G, Höllt V
O.-v.-Guericke University, Faculty of Medicine, Institute of Pharmacology and Toxicology, Leipzigerstr. 44, D-39120, Magdeburg, Germany.
Brain Res. 1999 Mar 27;823(1-2):191-7. doi: 10.1016/s0006-8993(99)01189-0.
Opioids are involved in the development of epileptic seizures. Recently, interest has been focused on the role of the kappa-opioid receptor agonists as novel approaches to the treatment of epilepsy. In the present study we investigated the effects of the kappa-opioid receptor agonist enadoline (Ena) on pentylenetetrazol (PTZ) induced seizures, PTZ kindling, shuttle-box performance and hippocampal neuromorphology. Ena injected i.c.v. in doses of 1 and 10 nmol did not affect acute PTZ seizures. In the course of PTZ kindling development, co-treatment (1 nmol) with the kappa-opioid receptor agonist suppressed seizure strength. Eight days after kindling completion the animals received a challenge dose of PTZ. In reaction to challenge, kindled animals which were pretreated with Ena reached significantly lower seizure scores. Kindling resulted in diminished shuttle-box performance. Learning performance in kindled animals pretreated with Ena was not normalised. Kindling resulted in increased glutamate binding. Interestingly, in comparison with the saline/saline group, neither in the Ena/saline nor in the Ena/PTZ treated groups changes in glutamate binding were found. That means that Ena prevented the increase in glutamate binding in the kindled group. In kindled animals significant cell loss in CA1 of the dorsal hippocampus was found and this was efficaciously counteracted by Ena. However, Ena alone did induce similar cell loss compared to kindled animals. It is hypothesised that the effects of enadoline are mainly due to interferences with glutamatergic systems.
阿片类药物与癫痫发作的发生有关。最近，人们的兴趣集中在κ-阿片受体激动剂作为治疗癫痫的新方法所起的作用上。在本研究中，我们研究了κ-阿片受体激动剂依那朵林（Ena）对戊四氮（PTZ）诱导的癫痫发作、PTZ点燃、穿梭箱行为表现和海马神经形态学的影响。脑室内注射1和10 nmol剂量的Ena对急性PTZ癫痫发作没有影响。在PTZ点燃发展过程中，与κ-阿片受体激动剂联合治疗（1 nmol）可抑制癫痫发作强度。点燃完成8天后，动物接受PTZ激发剂量。作为对激发的反应，用Ena预处理的点燃动物癫痫发作评分显著降低。点燃导致穿梭箱行为表现下降。用Ena预处理的点燃动物的学习行为表现未恢复正常。点燃导致谷氨酸结合增加。有趣的是，与生理盐水/生理盐水组相比，在Ena/生理盐水组和Ena/PTZ治疗组中均未发现谷氨酸结合的变化。这意味着Ena阻止了点燃组中谷氨酸结合的增加。在点燃动物中，发现背侧海马CA1区有明显的细胞丢失，而Ena有效地抵消了这种情况。然而，与点燃动物相比，单独使用Ena确实会诱导类似的细胞丢失。据推测，依那朵林的作用主要是由于对谷氨酸能系统的干扰。
