ROLES OF OPIOID PEPTIDES IN THE REGULATION OF HIPPOCAMPAL EXCITABILITY

阿片肽在海马神经元凋亡调控中的作用 兴奋性是一个深入研究的主题，因为发现 大脑中的内源性鸦片 阿片肽产生湿 狗样抖动（WDS）和癫痫样放电的大鼠时， 脑室注射。 本研究旨在 以获得进一步的信息来支持假设， 海马中的阿片肽可能在介导 白龙会和缉获活动。 特异性μ受体注射 激动剂，（N-MePhe 3，D-Pro）-morphiceptin（PL 017）和δ 受体激动剂，（D-Ala 2，D-Leu 5）-脑啡肽（DADLE）， 腹侧海马产生惊厥性发作， 这表明这两种受体都参与了 调解这些行为。 海马甘氨酸水平 和γ-氨基丁酸（GABA）增加， 在PL 017注射后天冬氨酸减少。 预处理 β-盐酸夫那普利胺（B-FNA），一种不可逆的 受体阻断剂，减弱PL 017诱导的WDS和 抽搐 它还恢复了PL 017诱导的细胞内的变化。 海马氨基酸水平与对照值相比。 这些结果表明，阿片类药物诱导的WDS和惊厥 癫痫发作是受体介导的， 通过减弱抑制剂的释放来解除抑制机制 海马体中的氨基酸 然而，退化 海马颗粒细胞的海马内注射 秋水仙碱减弱PL 017诱导的WDS，但增强了 抽搐的严重程度，因此表明这两个 行为可能是由不同的途径介导的， 海马体。 这些数据进一步证明了 海马中的阿片肽可能在 调节海马兴奋性。 研究计划， 确定阿片肽对营业额的影响， GABA的体内释放，以直接测试GABA 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.