权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Nicotinic Acetylcholine Receptors and Inhibitory Behavior

烟碱乙酰胆碱受体和抑制行为

基本信息

批准号：
8503602
负责人：
David J Bucci
金额：
$ 22.07万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8503602
关键词：
Acetylcholine Adolescence Adolescent Adult Affect Age Agonist Animal Model Animals Antismoking Attention Attention deficit hyperactivity disorder Behavior Behavioral Binding Sites Brain Cardiovascular Diseases Cessation of life Child Cigarette Smoker Clinical Cues Data Denervation Development Disease Dose Exhibits Female Functional disorder Hippocampus (Brain)Human Immunoglobulin G Immunotoxins Impaired cognition Impairment Impulsivity Inbred SHR Rats Injection of therapeutic agent Learning Left Lesion Link Literature Lung diseases Malignant Neoplasms Measures Medial Mediating Memory Mental disorders Methylphenidate Modeling Nicotine Nicotine Dependence Nicotinic Receptors Performance Persons Population Prefrontal Cortex Primates Procedures Rat Strains Rattus Reporting Research Rest Rewards Rodent Role Schizophrenia Sex Characteristics Signal Transduction Smoke Smoking Statutes and Laws Stimulus Structure System Techniques Testing Training Treatment Protocols United States Withholding Treatment Work addiction basal forebrain base brain behavior cholinergic cigarette smoking experience improved insight male neuromechanism neurotoxic nicotine abuse nicotine replacement public health relevance research study response smoking cessation success theories young adult

项目摘要

DESCRIPTION (provided by applicant): Although recent anti-smoking campaigns and legislation have achieved success in reducing the number of adult cigarette smokers, other populations have been not so positively affected. For instance, there continues to be high rates of nicotine use in adolescents as well as in various clinical populations, including those with schizophrenia or Attention- Deficit/Hyperactivity Disorder (ADHD). Despite substantial research, it remains unclear why nicotine use is high in these groups. Various theories have been proposed, including the notion that nicotine is used to alleviate dysfunctional reward systems and that nicotine is used to self-medicate for cognitive impairment. Nicotine has beneficial effects on functions such as attention and memory, lending support to the latter theory. However, little is known about the effects of nicotine and the role of nicotinic acetylcholine receptors in regulating inhibitory behavior. Deficits in inhibition are considered among the core impairments in ADHD and are also associated with schizophrenia. Likewise, normal adolescence is often characterized by impulsivity and inhibitory deficits. To fill this gap in the literature, the proposed experiments will determine how nicotine effects inhibition using an animal model of response inhibition that is analogous to inhibition tasks commonly used in research with humans. Our preliminary data indicate that nicotine specifically enhances the ability of rats to withhold a learned response, as has been observed in humans with ADHD. Thus, the first objective will be to determine which subtype(s) of nicotinic acetylcholine receptor mediates the beneficial effects of nicotine on inhibition. This will be done using pharmacological approaches in both normal rats and a strain of rats commonly used as a model of ADHD. The second objective is to determine the brain systems through which nicotine affects inhibition. These studies will use a combination of approaches consisting of selective cholinergic denervation of the prefrontal cortex or hippocampus, and treatment with nicotinic receptor subtype-specific compounds. Finally, the third objective is to test for sex differences in the effects of nicotine on inhibitory behavior. These final experiments are based on growing reports of sex differences in cognitive dysfunction in disorders such as ADHD and differences in smoking rates between males and females. Together, these results of the proposed studies will provide new insight into how nicotine affects inhibitory behavior and promote the development of enhanced smoking cessation and treatment regimens.

描述(申请人提供)：尽管最近的反吸烟运动和立法在减少成年吸烟人数方面取得了成功，但其他人口并没有受到如此积极的影响。例如，青少年以及各种临床人群中尼古丁的使用率仍然很高，包括精神分裂症或注意力缺陷/多动障碍(ADHD)患者。尽管进行了大量研究，但仍不清楚为什么尼古丁在这些群体中的使用率很高。人们提出了各种各样的理论，包括尼古丁被用来缓解功能失调的奖赏系统，尼古丁被用来自我治疗认知障碍。尼古丁对注意力和记忆力等功能有有益的影响，支持后一种理论。然而，关于尼古丁的作用和烟碱型乙酰胆碱受体在调节抑制行为中的作用，人们知之甚少。抑制缺陷被认为是ADHD的核心损害之一，也与精神分裂症有关。同样，正常的青春期通常以冲动和抑制缺陷为特征。为了填补文献中的这一空白，拟议中的实验将使用反应抑制的动物模型来确定尼古丁如何影响抑制作用，该动物模型类似于人类研究中常用的抑制任务。我们的初步数据表明，尼古丁特别增强了大鼠抑制习得性反应的能力，就像在患有ADHD的人类身上观察到的那样。因此，第一个目标将是确定烟碱型乙酰胆碱受体的哪一亚型(S)介导尼古丁抑制的有益效果。这将在正常大鼠和通常用作ADHD模型的一种品系的大鼠身上使用药理学方法来完成。第二个目标是确定尼古丁影响抑制的大脑系统。这些研究将采用多种方法相结合的方法，包括选择性前额叶皮质或海马区的胆碱能去神经，以及尼古丁受体亚型特异性化合物的治疗。最后，第三个目标是测试尼古丁对抑制行为的影响的性别差异。这些最终的实验是基于越来越多的关于性别差异、ADHD等疾病的认知功能障碍以及男性和女性吸烟率差异的报道。总之，这些拟议研究的结果将为尼古丁如何影响抑制行为提供新的见解，并促进加强戒烟和治疗方案的发展。