Effects of the competitive nicotinic antagonist erysodine on behavior occasioned or maintained by nicotine: comparison with mecamylamine
Effects of the competitive nicotinic antagonist erysodine on behavior occasioned or maintained by nicotine: comparison with mecamylamine
复制标题
DOI：
10.1007/s002130050047
复制
发表时间：
2000-02-01
影响因子：
3.4
通讯作者：
Rovetti, CC
中科院分区：
文献类型：
--
作者：
Mansbach, RS;Chambers, LK;Rovetti, CC
基本原理：尼古丁的细胞效应是其成瘾倾向的基础，被认为是由中枢神经系统中的神经元烟碱受体（nACHR）介导的。据信，中枢神经系统中密集表达的含β 2的nACHR负责这些作用，但几乎没有数据可以直接评估尼古丁的急性主观和强化作用的亚型介导。目的：本研究比较了竞争性nACHR拮抗剂Erysodine和非竞争性拮抗剂美加明在训练辨别或自我给予尼古丁的大鼠中的作用。训练成年雄性大鼠在食物维持行为的两级程序中区分0.4 mg/kg尼古丁注射液和溶媒，或在固定比例或渐进比例强化方案下自我注射0.03 mg/kg尼古丁。在杠杆按压的食物维持程序下训练另外的大鼠。结果如下：Erysodine（0.3-10 mg/kg）和mecamylamine（0.1-1.0 mg/kg）阻断尼古丁辨别，尽管只有Erysodine产生了预期竞争性拮抗剂的α-位移。Erysodine（0.32-32 mg/kg）和美加明（0.32-3.2 mg/kg）也选择性地减少了固定比例方案下的尼古丁自我给药，并降低了渐进比例方案下的断点。结论：基于已知的刺桐定对α 4 β 2 nACHR的亲和力及其相对于α 7和α 1 β 1 γ δ受体的选择性，本数据支持含β 2的nACHR构建体在尼古丁的辨别和增强作用中的关键作用。
Rationale: The cellular effects of nicotine underlying its addictive liability are thought to be mediated by neuronal nicotinic receptors (nACHRs) in the central nervous system. It is believed that densely expressed beta 2-containing nACHRs in the central nervous system are responsible for these actions, but few data are available that can directly assess subtype mediation of nicotine's acute subjective and reinforcing effects. Objective: The present study compared the effects of the competitive nACHR antagonist erysodine and the noncompetitive antagonist mecamylamine in rats trained to discriminate or self-administer nicotine, Methods: Adult male rats were trained to disciminate 0.4-mg/kg injections of nicotine from vehicle in a two-lever procedure of food-maintained behavior, or to self-administer 0.03-mg/kg injections of nicotine under fixed-ratio 5 or progressive-ratio schedules of reinforcement. Additional rats were trained under a food-maintained procedure of lever pressing. Results: Erysodine (0.3-10 mg/kg) and mecamylamine (0.1-1.0 mg/kg) blocked nicotine discrimination, although only erysodine produced the rightward shift that would be predicted of a competitive antagonist. Erysodine (0.32-32 mg/kg) and mecamylamine (0.32-3.2 mg/kg) also selectively reduced nicotine self-administration on a fixed-ratio schedule and lowered break points on a progressive-ratio schedule. Conclusions: Based on the known affinity of erysodine for alpha 4 beta 2 nACHRs and its selectivity relative to alpha 7 and alpha 1 beta 1 gamma delta receptors, the present data support a critical role of beta 2-containing nACHR constructs in the discriminative and reinforcing actions of nicotine.