SITES AND MECHANISMS FOR NICOTINES ACTION IN THE BRAIN
SITES AND MECHANISMS FOR NICOTINES ACTION IN THE BRAIN
复制标题
DOI：
10.1016/0149-7634(81)90018-x
复制
发表时间：
1981-01-01
影响因子：
8.2
通讯作者：
BIDLACK, JM
中科院分区：
文献类型：
--
作者：
ABOOD, LG;REYNOLDS, DT;BIDLACK, JM
进行了各种药理学、行为学和受体结合研究，以确定尼古丁对大鼠大脑的作用机制和作用部位。将尼古丁注入大鼠的侧脑室或第四脑室或直接注入前庭外侧核时，会产生特征性虚脱，通常伴有强直性癫痫发作和身体沿纵轴沿着旋转。在研究的各种脑区中，虚脱反应只能从外侧前庭核引出，在较小程度上，内侧前庭核也能引出。该反应不能由多种胆碱能激动剂产生，也不能用烟碱胆碱能拮抗剂拮抗，可能的例外是美加明。尼古丁类似物对抗尼古丁引起的大鼠虚脱的能力与其竞争~ 3 H-尼古丁结合大鼠脑膜的能力有很好的相关性，~ 3 H-尼古丁结合具有高度的亲和力和立体选择性，并集中在神经末梢和丘脑、大脑、海马等脑区。当大鼠脑室注射尼古丁时，它显著提高了厌恶性休克的阈值。得出的结论是，尼古丁的许多中枢作用不能解释传统的烟碱胆碱能机制的基础上。
A variety of pharmacologic, behavioral, and receptor-binding studies were performed in an effort to determine the mechanism and site of action of nicotine on the rat brain. When nicotine was given into the lateral or fourth ventricles or directly into the lateral vestibular nuclei of rats, it produced a characteristic prostration often accompanied by tonic seizures and body rotation along a longitudinal axis. Of a variety of brain areas studied, the prostration response could only be elicited from the lateral and, to a lesser extent, medial vestibular nuclei. The response could not be produced by a variety of cholinergic agonists or antagonized with nicotinic cholinergic antagonists, with the possible exception of mecamylamine. A good correlation was observed between the ability of nicotine analogues to antagonize the nicotine-induced prostration and their ability to compete with3H-nicotine binding to rat brain membranes.3H-nicotine binding had a high affinity, was stereoselective and concentrated in nerve endings and such brain regions as the thalamus, cerebrum, and hippocampus. When nicotine was administered intraventricularly to rats, it significantly elevated the threshold to an aversive shock. It was concluded that many of the central actions of nicotine could not be explained on the basis of traditional nicotinic cholinergic mechanisms.