ROLES OF OPIOID PEPTIDES IN THE REGULATION OF HIPPOCAMPAL EXCITABILITY

阿片肽在海马区调节中的作用 自从这一发现以来，兴奋性一直是人们深入研究的主题 大脑中内源性鸦片类药物的数量。阿片肽产生湿 犬抖动(WDS)和大鼠癫痫样放电 脑室内注射。这项研究的目的是 为了获得进一步的信息来支持这样的假设 海马体中的阿片肽可能起到中介作用 WDS和癫痫发作活动。注射特异性Mu受体 激动剂、(N-MePhe3，D-Pro)-吗啡肽(PL017)和Delta 受体激动剂(D-丙氨酸，D-亮氨酸)-脑啡肽(DADLE) 腹侧海马区引起惊厥发作和许多 WDS，提示这两种受体都参与了 调解这些行为。大鼠海马区甘氨酸水平 和γ-氨基丁酸(GABA)升高，但 注射PL017后天冬氨酸氨基转移酶降低。用来进行前处理 一种不可逆转的药物--β-呋喃三胺盐酸盐 受体阻滞剂，减弱PL017诱导的WDS和 抽搐。它还恢复了PL017诱导的大鼠脑缺血再灌注损伤。 海马区氨基酸水平接近对照水平。 这些结果表明，鸦片类药物引起的WDS和惊厥 癫痫发作是受体介导的，可能通过一种 抑制物释放减弱的解抑机制 海马体中的氨基酸。尽管如此，这种退化 海马内注射三七总皂甙对大鼠海马颗粒细胞的影响 秋水仙碱可减弱PL017诱导的WDS，但增强 抽搐的严重程度，因此表明这两人 行为可能由不同的途径在不同的 海马体。这些数据进一步证明了 海马体中的阿片肽可能在 调节海马区兴奋性。研究计划是为了 确定阿片肽对周转或体内代谢的影响 体内释放GABA直接检验GABA的假说 可能介导阿片肽的兴奋性作用 海马体。

Roles of opioid peptides in the regulation of hippocampal excitability are a subject of intensive study since the discovery of endogenous opiates in the brain. Opiate peptides produce wet dog shakes (WDS) and epileptiform discharges in rats when administered intraventricularly. The purpose of this study was to obtain further information to support the hypothesis that opioid peptides in the hippocampus may play a role in mediating WDS and seizures activities. Injections of specific mu receptor agonist, (N-MePhe3, D-Pro)-morphiceptin (PL017), and delta receptor agonist, (D-Ala2, D-Leu5)-enkephalin (DADLE), to the ventral hippocampus produced convulsive seizures and numerous WDS, suggesting that both receptors are involved in the mediation of these behaviors. The levels of hippocampal glycine and gamma-aminobutyric acid (GABA) were increased but aspartate was reduced after PL017 injection. Pretreatment with beta-funaltrexamine hydrochloride (B-FNA), an irreversible mu receptor blocker, attenuated PL017-induced WDS and convulsions. It also restored the PL017-induced changes in the levels of hippocampal amino acids to that of control values. These results suggest that opiate-induced WDS and convulsive seizures are receptor mediated and may be acting through a disinhibition mechanism by attenuating the release of inhibitory amino acids in the hippocampus. Nevertheless, the degeneration of hippocampal granule cells by intrahippocampal injection of colchicine attenuated PL017-induced WDS but potentiated the severity of convulsions, therefore suggesting that these two behaviours may be mediated by different pathways in the hippocampus. These data give further evidence to the idea that opioid peptides in the hippocampus may play an important role in regulating hippocampal excitability. Studies are planned to determine the effects of opioid peptides on the turnover or in vivo release of GABA to directly test the hypothesis that GABA may mediate the excitability effect of opioid peptides in the hippocampus.