Neurochemical and behavioral effects of bupropion and mecamylamine in the presence of nicotine.
Neurochemical and behavioral effects of bupropion and mecamylamine in the presence of nicotine.
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尼古丁存在下安非他酮和美加明的神经化学和行为影响。
DOI：
10.1016/j.brainres.2006.07.110
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发表时间：
2006
期刊：
影响因子：
2.9
通讯作者：
Robinson,SusanE
中科院分区：
文献类型：
--
作者：
Vann,RobertE;Rosecrans,JohnA;James,JohnR;Philibin,ScottD;Robinson,SusanE
安非他酮是一种戒烟药物，其主要作用机制通常被认为涉及多巴胺能系统，尽管有证据表明安非他酮对烟碱型乙酰胆碱受体(NAChRs)也有影响。这项研究评估了尼古丁在安非他酮和nAChR拮抗剂甲戊胺存在时对反应率的干扰效应，以及这些药物改变尼古丁刺激的不同脑区nAChR功能的能力。训练大鼠在可变间隔15(VI15)计划下在单杆上做出反应，以加强食物。最初，绘制了尼古丁、安非他酮和甲氨基酚的剂量效应曲线。在确定有效的尼古丁剂量(1.2 mg/kg)以完全阻断反应率后，已确定甲氨基甲胺和安非他酮均可阻断尼古丁的减速作用。这一结果表明，在尼古丁存在的情况下，安非他酮与甲氨基甲胺具有相同的行为效应。为了进一步探讨这一关系，我们研究了安非他酮或甲氨基丁胺对尼古丁刺激的86Rb+外流的影响，这些突触小体来自额叶皮质、海马、纹状体和丘脑。与对照组相比，解剖前15分钟给予3.0 mg/kg甲氨基甲胺(S.C.)的大鼠，尼古丁刺激的所有脑区的86Rb+外流明显减少。相比之下，解剖前15分钟给予30.0 mg/kg安非他酮(S.C.)的大鼠，与对照组相比，所有脑区尼古丁刺激的86Rb+外流显著增加。综上所述，这些结果表明，当尼古丁存在时，安非他酮引起了独特的药理差异，从而显示出nAChR激动剂和拮抗剂样效应。
The primary mechanism of action of bupropion, a smoking cessation drug, is commonly believed to involve the dopaminergic system although evidence exists that bupropion also has effects at nicotinic acetylcholine receptors (nAChRs). This study evaluated the disruptive effects of nicotine on response rates in the presence of bupropion and the nAChR antagonist, mecamylamine, as well as the ability of these drugs to alter nicotine-stimulated nAChR function in various brain areas. Rats were trained to respond on a single lever under a variable interval 15 (VI15) schedule for food reinforcement. Initially, dose effect curves were generated for nicotine, bupropion and mecamylamine. Upon determining the dose of nicotine (1.2 mg/kg) effective in completely disrupting rates of responding, it was established that both mecamylamine and bupropion block nicotine's rate-reducing effects. This result suggests that bupropion shares behavioral effects with mecamylamine when administered in the presence of nicotine. To explore this relationship further, the effect of in vivo administration of bupropion or mecamylamine on nicotine-stimulated86Rb+efflux was studied in synaptosomes prepared from the frontal cortex, hippocampus, striatum and thalamus. Nicotine-stimulated86Rb+efflux from all brain regions was significantly reduced in rats administered 3.0 mg/kg mecamylamine (s.c.) 15 min prior to dissection compared to control rats. In contrast, a significant increase in nicotine-stimulated86Rb+efflux was observed in all brain regions from rats administered 30.0 mg/kg bupropion (s.c.) 15 min prior to dissection compared to control rats. Taken together these results demonstrate that when administered in the presence of nicotine, bupropion elicits unique pharmacological differences such that it exhibits both nAChR agonist- and antagonistic-like effects.