NARCOTIC TOLERANCE AND PHYSICAL DEPENDENCE MECHANISMS

阿片耐受和身体依赖的机制 发展正在调查中。 有人提出了一个假设， 阿片作用是基于阿片-Ca ++相互作用。 急性阿片类药物 作用归因于神经元Ca++的降低， 减少引起的神经元活动抑制 神经递质释放 耐受性来自于一种反适应性 神经元Ca ~（++）降低的反应，其结果是Ca ~（++） 拮抗阿片作用的蓄积（耐受性）。 的能力 频繁重复给予阿片类药物后保留Ca++变得依赖 阿片类药物的存在（身体依赖）和 阿片类药物导致细胞质Ca++和神经递质释放增加 和戒断综合症 为了验证这一假设，对急性 和慢性阿片类药物对钙流的影响正在进行 突触体、肥大细胞和红细胞。 药理学研究也在分离的组织上进行， 器官制备物如豚鼠回肠和输精管 小鼠、大鼠和家兔，以确定mu、kappa和delta的重要性 受体的耐受性和依赖性。

The mechanisms involved in opiate tolerance and physical dependence development are under investigation. A hypothesis has been proposed for opiate action that is based on opiate-Ca++ interactions. Acute opiates effects are attributed to a lowering of neuronal Ca++ with consequent inhibition of neuronal activity resulting from a decrease in neurotransmitter release. Tolerance results from a counteradaptive response on the lowering of neuronal Ca++ and the consequence is Ca++ accumulation which antagonizes opiate effects (tolerance). The ability to retain Ca++ after frequent repeated opiate administration becomes dependent on the presence of the opiate (physical dependence) and discontinuance of the opiate results in increased cytosol Ca++ and neurotransmitter release and the withdrawal syndrome. To validate the hypothesis, studies on acute and chronic opiate administration on calcium flux are being carried out on synaptosomes, mast cells and red blood cells of the mouse and rat. Pharmacologic studies are also being performed on the isolated tissue or organ preparations such as the guinea pig ileum and the vas deferens of the mouse, rat and rabbit to define the importance of mu, kappa and delta receptors in tolerance and dependence.