EFFECTS OF NICOTINE ON BEHAVIOR--SITE/MECHANISM & ACTION

尼古丁对行为的影响——部位/机制

• 批准号: 3208963
• 负责人: JOHN A ROSECRANS
• 金额: $ 7.79万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-03-01 至 1990-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3208963
• 关键词: acetylcholine; anticholinergic agent; atropine; behavioral medicine; brain mapping; caudate nucleus; cerebral cortex; cholinergic agents; dosage; hippocampus; mecamylamine; nicotine; nucleus accumbens; physostigmine; psychopharmacology; reticular formation; sensory discrimination

The major objective of this research will be to determine brain area sites an cholinergic mechanisms important to nicotine's effects on behavior. Previous research conducted in this laboratory has indicated that neurons in the hippocampus (Hp) and midbrain reticular formation (MRF) are somehow involved in the ability nicotine (400 microgram/kg, s.c.) to exert discriminative stimulus (DS) control of behavior. In addition the nicotine- induced DS appeared to have a non-cholinergic component as we were unable to mimic the nicotine DS by increasing brain acetylcholine (ACh) levels via the administration of phsostigmine (250 microgram/kg, s.c.) muscarinic receptors were blocked by atropine. The major direction of the research to be conducted will further define the nature of the nicotine-induce DS. Thus, we will initially study the role of the HP and MRF further using different nicotine training doses (100 and 200 microgram/kg) and will study the generalization of the peripherally-induced DS to each brain site by perfusing a given site with nicotine and other cholinergic agonists using an EMIT perfusion apparatus. This central perfusion approach will be used to evaluate other brain area sites in relation to the peripherally-mediated nicotine DS and will also be utilized to study the effects of nicotinic and muscarinic stimulation on other operant behaviors as well. Thus, in addition to studying the importance of a given brain area site to the DS properties of nicotine we will also attempt to characterize each brain area site as it relates to the effects of nicotinic/muscarinic stimulation and/or inhibition on simple operant behaviors. Such an approach will provide information important to both nicotine's effects on behavior and the importance of specific cholinergic neurons (muscarinic and nicotinic) to behavior. A major goal of this research will be to identify nicotinic sites sensitive to ACh using in vivo behavioral approaches. To date few investigators have demonstrated that ACh-elicited effects can be antagonized by nicotinic receptor antagonist such as mecamylamine; most direct or indirect-elicited ACh effects are antagonized the muscarinic antagonists atropine. This aspect of the research will be studied using the perfusion of brain area sites with ACh analogs such as methacholine with the goal of demonstrating that a given behavioral effect can be selectively antagonized by muscarinic and/or nicotinic antagonists.

这项研究的主要目标是确定大脑 胆碱能机制对尼古丁很重要的区域 对行为的影响。 此前在这方面进行的研究 实验室表明，海马体 (Hp) 和 中脑网状结构（MRF）以某种方式参与 尼古丁（400微克/公斤，SC）发挥辨别力的能力 刺激（DS）行为控制。 此外，尼古丁—— 诱导的 DS 似乎具有非胆碱能成分，因为我们 无法通过增加大脑来模仿尼古丁 DS 通过使用扁扁豆碱来调节乙酰胆碱 (ACh) 水平 （250 微克/千克，皮下注射）毒蕈碱受体被阻断 阿托品。 拟开展研究的主要方向 将进一步定义尼古丁诱导 DS 的性质。 因此，我们 将首先进一步研究 HP 和 MRF 的作用 不同的尼古丁训练剂量（100 和 200 微克/公斤）和 将研究外周诱导 DS 的泛化 通过向特定部位灌注尼古丁和其他物质来控制每个大脑部位 使用 EMIT 灌注装置的胆碱能激动剂。 这 中心灌注方法将用于评估其他大脑 与外周介导的尼古丁 DS 相关的区域位点和 还将用于研究烟碱和 毒蕈碱刺激也对其他操作行为产生影响。 因此， 除了研究特定大脑区域部位的重要性 对于尼古丁的 DS 特性，我们还将尝试 描述每个大脑区域部位的特征，因为它与以下因素的影响有关 烟碱/毒蕈碱刺激和/或抑制简单 操作行为。 这种方法将提供信息 对于尼古丁对行为的影响和 特定胆碱能神经元（毒蕈碱和 烟碱）影响行为。 这项研究的一个主要目标是 使用体内行为识别对 ACh 敏感的烟碱位点 接近。 迄今为止，很少有研究人员证明 烟碱受体可以拮抗乙酰胆碱引起的作用 拮抗剂例如美加明；最直接或间接诱发的 乙酰胆碱的作用被毒蕈碱拮抗剂阿托品所拮抗。 这方面的研究将使用灌注进行研究 具有乙酰胆碱类似物的大脑区域位点，例如乙酰甲胆碱 目的是证明给定的行为效果可以 被毒蕈碱和/或烟碱选择性拮抗 对手。