Mecamylamine, dihydro-beta-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine.
Mecamylamine, dihydro-beta-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine.
复制标题
DOI：
10.1016/j.pbb.2009.09.012
复制
发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Bevins RA
中科院分区：
文献类型：
--
作者：
Struthers AM;Wilkinson JL;Dwoskin LP;Crooks PA;Bevins RA
目前的吸烟者表达了戒烟的愿望。然而，大多数人发现很难保持禁欲。因此，研究工作不断寻求开发更有效的治疗方法。一个这样的研究领域涉及尼古丁的内感受性刺激效应，无论是在操作性药物辨别任务中作为辨别性刺激，还是最近在辨别性目标跟踪任务中作为条件刺激（CS）。本研究使用对β2*、α7*、α6β2* 和α3β4* 受体具有不同选择性的拮抗剂，研究了烟碱乙酰胆碱受体在尼古丁（0.4 mg/kg）CS效应中的潜在作用。甲基乌头碱（MLA）对尼古丁诱发的条件反应无影响。美加明和二氢-β-赤藓啶（DHβE）剂量依赖性地阻断尼古丁CS诱发的反应。在美加明和DHβE的时程评估中，当在测试前5分钟给药时，每种都阻断了条件反应，当在测试前200分钟给药时，仍然阻断了条件反应。两种新的双吡啶类似物（N，N '-（3，3'-（dodecan-1，12-diyl）-bis-picolinium dibromide [bPiDDB]和N，N '-（decan-1，10-diyl）-bis-picolinium diodide [bPiDI]）不阻断尼古丁诱发的条件性反应。最后，使用美加明、美沙芬和/或安非他酮的低剂量组合进行预处理以靶向α3β4* 受体。没有组合阻断训练剂量的尼古丁诱发的条件反应。然而，美加明和美沙芬的组合部分阻断了尼古丁诱发的对较低剂量尼古丁（0.1 mg/kg）的条件反应。这些结果表明，β2* 和潜在的α3β4* 烟碱乙酰胆碱受体在尼古丁的CS效应中发挥作用，并且是开发尼古丁戒烟辅助药物的潜在靶点。
Current smokers express the desire to quit. However, the majority find it difficult to remain abstinent. As such, research efforts continually seek to develop more effective treatment. One such area of research involves the interoceptive stimulus effects of nicotine as either a discriminative stimulus in an operant drug discrimination task, or more recently as a conditional stimulus (CS) in a discriminated goal-tracking task. The present work investigated the potential role nicotinic acetylcholine receptors in the CS effects of nicotine (0.4 mg/kg) using antagonists with differential selectivity for β2*, α7*, α6β2*, and α3β4* receptors. Methyllycaconitine (MLA) had no effect on nicotine-evoked conditioned responding. Mecamylamine and dihydro-β-erythroidine (DHβE) dose dependently blocked responding evoked by the nicotine CS. In a time-course assessment of mecamylamine and DHβE, each blocked conditioned responding when given 5 min before testing and still blocked conditioned responding when administered 200 min before testing. Two novel bis-picolinium analogs (N, N’-(3, 3′-(dodecan-1,12-diyl)-bis-picolinium dibromide [bPiDDB], and N, N’-(decan-1,10-diyl)-bis-picolinium diiodide [bPiDI]) did not block nicotine-evoked conditioned responding. Finally, pretreatment with low dose combinations of mecamylamine, dextromethorphan, and/or bupropion were used to target α3β4* receptors. No combination blocked conditioned responding evoked by the training dose of nicotine. However, a combination of mecamylamine and dextromethorphan partially blocked nicotine-evoked conditioned responding to a lower dose of nicotine (0.1 mg/kg). These results indicate that β2* and potentially α3β4* nicotinic acetylcholine receptors play a role in the CS effects of nicotine and are potential targets for the development of nicotine cessation aids.
登录
查看更多内容
影响因子：
3.4
作者：
Miller, DK;Wilkins, LH;Dwoskin, LP
通讯作者：
Dwoskin, LP
影响因子：
2.9
作者：
Bevins, RA;Besheer, J
通讯作者：
Besheer, J
影响因子：
3
作者：
Gentry, C. L.;Lukas, R. J.
通讯作者：
Lukas, R. J.
影响因子：
4.7
作者：
BENWELL, MEM;BALFOUR, DJK;ANDERSON, JM
通讯作者：
ANDERSON, JM
影响因子：
3.4
作者：
Besheer, J;Palmatier, MI;Bevins, RA
通讯作者：
Bevins, RA