MORPHINE-TOLERANCE AND PHYSICAL-DEPENDENCE - INFLUENCE OF CHOLINERGIC AGONISTS AND ANTAGONISTS
MORPHINE-TOLERANCE AND PHYSICAL-DEPENDENCE - INFLUENCE OF CHOLINERGIC AGONISTS AND ANTAGONISTS
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DOI：
10.1016/0014-2999(76)90259-4
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发表时间：
1976-01-01
影响因子：
5
通讯作者：
WAY, EL
中科院分区：
文献类型：
--
作者：
BHARGAVA, HN;WAY, EL
在对吗啡耐受和依赖的小鼠（M小鼠）和未处理小鼠（N小鼠）中评估了改变胆碱能活性的中枢作用剂的作用。在N和M小鼠中，毒扁豆碱均轻微增强吗啡镇痛作用，且该作用可被阿托品和东莨菪碱阻断。在纳洛酮给药前10 min给药，阿托品可增强依赖小鼠的快速戒断跳跃反应;在纳洛酮给药前30 min给药，阿托品可抑制该反应。毒扁豆碱和氧化震颤素对跳跃反应有明显抑制作用，而乙硫磷则无此作用。毒扁豆碱对纳洛酮催促戒断跳跃的抑制作用可被阿托品和东莨菪碱逆转，但阿托品不改变吗啡耐受和依赖的形成。毒扁豆碱使N和M小鼠脑乙酰胆碱（ACh）水平升高，M小鼠的升高幅度更大。预先给予阿托品或东莨菪碱可阻断这种增加。在处死前10分钟给予M小鼠阿托品时，脑ACh水平降低。然而，当脑乙酰胆碱水平测定30分钟后阿托品，没有变化被发现。它的结论是，乙酰胆碱不发挥主要的，直接的作用，在发展中的耐受性和依赖性，但乙酰胆碱参与的表现急性吗啡效应和在依赖状态下的一些戒断症状。
The effects of centrally acting agents which alter cholinergic activity were assessed in mice rendered tolerant to and dependent on morphine (M mice) and in naive mice (N mice). In both N and M mice, physostigmine potentiated morphine analgesia slightly, and this action was blocked by atropine and scopolamine. When administered 10 min before naloxone in dependent mice atropine enhanced precipitated withdrawal jumping; when given 30 min before naloxone, atropine produced an inhibition of the response. Physostigmine and oxotremorine greatly inhibited the jumping response, while echothiophate had no effect. The inhibitory effect of physostigmine on naloxone precipitated withdrawal jumping was reversed by atropine and scopolamine but atropine did not alter morphine tolerance and dependence development. Brain acetylcholine (ACh) levels in both N and M mice were increased by physostigmine, the increase being greater in M mice. This increase was blocked by prior administration of atropine or scopolamine. When atropine was administered to M mice 10 min before sacrifice, brain ACh levels decreased. However, when brain ACh levels were determined 30 min after atropine, no change was found. It was concluded that ACh does not play a major, direct role in the development of tolerance and dependence, but that ACh is involved in the manifestations of acute morphine effects and in some of the withdrawal signs in the dependent state.