OPIOID-CHOLINERGIC INTERACTIONS IN THE HIPPOCAMPUS

这项拟议的工作试图定义阿片类药物之间的相互作用 海马体中的多肽和乙酰胆碱。尽管有 有证据表明这两个系统在记忆和 在海马体中的癫痫发作活动，关于 这两个系统之间的相互作用。美国政府的影响 海马区主要阿片肽--脑啡肽和强啡肽A-- 关于生物化学和行为反应与 将对毒鼠强胆碱能系统进行研究。这个 实验旨在区分直接阿片类药物和 影响和那些通过胆碱能介导的作用 系统。典型的Mu(DAGO)，Delta((D-Pen 2，5)脑啡肽) 和Kappa(强啡肽A)激动剂将被检查其 在不同程度上影响毒鼠强系统的能力。 生化指标包括第二信使系统、密度 M受体和乙酰胆碱的亚型分布 放手。第二个要检查的信使系统是 磷脂酰肌醇周转和腺苷环化酶及GTP酶 活性，将利用体外切片和 膜制剂。急性和慢性疾病的影响 海马区注射阿片肽对毒鼠强的影响 受体将用放射自显影进行检查，使用(~3H)- 非选择性配基苯甲酸奎宁酯及其抑制作用 以哌仑西平和加拉胺为选择性M_1和M_2 分别是对抗者。乙酰胆碱释放的评估是通过 预加载的超融合切片的钾刺激 用(~3H)-胆碱。急、慢性阿片类药物治疗的效果 关于表象记忆(即依赖于线索的记忆 在选择的时间出现)是通过大鼠的表现来衡量的 在T形迷宫中完成配对交替任务。慢性病的影响 阿片类药物治疗哌仑西平所致记忆障碍 加兰明诱发的癫痫发作将提供有关 M受体介导的具有亚型特异性的行为。 海马体是一种已知与记忆有关的结构 以及人类和实验动物的癫痫发作。 阿片类药物与毒扁豆碱系统之间的相互作用 海马体可能在人类中起作用，并有助于 与药物滥用有关的行为问题。

The proposed work seeks to define the interaction between opioid peptides and acetylcholine in the hippocampus. Although there is evidence that both systems play important roles in memory and seizure activity in the hippocampus, there is little information on the interactions between the two systems. The effect of the major hippocampal opioid peptides--enkephalins and dynorphin A-- on biochemical and behavioral responses associated with the muscarinic cholinergic system will be investigated. The experiments are designed to distinguish between direct opioid effects and those that are mediated through the cholinergic system. Prototypical mu (DAGO), delta ((D-Pen 2,5) enkephalin) and kappa (dynorphin A) agonists will be examined for their abilities to affect the muscarinic system at different levels. Biochemical measures include second messenger systems, density and subtype distribution of muscarinic receptors and acetylcholine release. The second messenger systems to be examined are phosphtidylinositol turnover and adenylate cyclase and GTPase activities, which will be measured utilizing in vitro slice and membrane preparations. The effects of acute and chronic intrahippocampal injections of the opioid peptides on muscarinic receptors will be examined by autoradiography using (3H)- quinuclidinyl benzilate as a non-selective ligand and its inhibition by pirenzepine and gallamine as selective M1 and M2 muscarinic antagonists, respectively. Acetylcholine release is assessed by potassium-stimulated of superfused slices, which are preloaded with (3H)-choline. Effects of acute and chronic opioid treatment on representational memory (i.e., memory dependent on cues not present at the time of choice) is measured by performance of rats on a paired alternation task in a T-maze. The effects of chronic opioid treatment on memory impairments induced by pirenzepine and seizures induced by gallamine will provide information on muscarinic receptor-mediated behaviors that are subtype specific. The hippocampus is a structure known to be involved in memory and seizures in both humans and experimental animals. Interactions between opioid and muscarinic systems in the hippocampus may be operative in humans and contribute to behavioral problems associated with drug abuse.