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.

这项研究的主要目的是确定大脑 区域部位对尼古丁很重要的胆碱能机制 对行为的影响。 以前进行的研究 实验室表明，海马（HP）和 中脑网状形成（MRF）以某种方式参与 能力尼古丁（400微克/千克，S.C。）发挥歧视性 刺激（DS）控制行为。 此外，尼古丁 - 当我们 无法通过增加大脑来模仿尼古丁DS 乙酰胆碱（ACH）通过pHsostigmine给药 （250微克/kg，S.C。）毒蕈碱受体被阻断 阿托品。 要进行的研究的主要方向 将进一步定义尼古丁诱导的DS的性质。 因此，我们 最初将进一步研究HP和MRF的作用 不同的尼古丁训练剂量（100和200微克/kg）和 将研究周围诱导的DS的概括 每个大脑站点都通过培养给定的尼古丁和其他位置 胆碱能激动剂使用发射灌注设备。 这 中央灌注方法将用于评估其他大脑 与周围介导的尼古丁DS和 还将用于研究烟碱和 对其他操作行为的毒蕈碱刺激也是如此。 因此， 除了研究给定大脑区域部位的重要性 对于尼古丁的DS属性，我们还将尝试 表征每个大脑区域位点，因为它与 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）行为。 这项研究的主要目标是 识别使用体内行为对ACH敏感的烟碱位点 方法。 迄今为止，很少有调查人员证明 烟碱受体可以拮抗ACH引起的效果 拮抗剂，例如梅卡米胺；最直接或间接的 ACH效应拮抗毒蕈碱拮抗剂阿托品。 研究的这一方面将通过灌注来研究 带有ACH类似物的大脑区域位点，例如甲基胆碱 证明给定的行为效应的目标是 由毒蕈碱和/或烟碱有选择地拮抗 对手。