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Role of Monoamine Oxidases in Tobacco Addiction

单胺氧化酶在烟草成瘾中的作用

基本信息

批准号：
7379939
负责人：
FRANCES M. LESLIE
金额：
$ 24.85万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-01 至 2009-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7379939
关键词：
Acetaldehyde Adrenergic Receptor Adult Affect Amphetamines Animal Model Animals Attention Behavioral Biochemical Brain Chronic Classification Cocaine Condition Daily Dependence Dose Evaluation FOS gene Female Goals Implant Injection of therapeutic agent Lead Measures Mecamylamine Messenger RNA Microdialysis Modeling Monoamine Oxidase Monoamine Oxidase A Monoamine Oxidase B Monoamine Oxidase Inhibitors Naloxone Neurons Nicotine Nicotine Withdrawal Nicotinic Receptors Opioid Receptor Pharmaceutical Preparations Phase Procedures Rate Rattus Relapse Relative (related person)Reporting Research Research Personnel Rewards Role Saline Self Administration Smoking System Techniques Testing Tobacco Tobacco Dependence Tobacco smoke Tobacco use Tranylcypromine Withdrawal Withdrawal Symptom base cigarette smoking cigarette smoking day design drug of abuse improved male monoamine neural circuit neurochemistry programs psychologic psychostimulant research study response

项目摘要

Although current research into the causes of smoking focuses largely on nicotine, there is accumulating evidence that other tobacco constituents, such as monoamine oxidase (MAO) inhibitors, may increase the addictive liability of tobacco use. The goal of the proposed research is to elucidate the contribution of MAO inhibition to the psychoactive effects of tobacco. We will use the rat as a model to test the hypothesis that MAO inhibition enhances the effects of nicotine on smoking initiation and dependence. We base this hypothesis on prior findings that i) MAO is an important modulator of monoamines in brain reward systems, ii) smoking reduces brain MAO activity thereby increasing brain monoamines, and iii)MAO inhibition enhances nicotine-induced locomotor sensitization and reward. We propose to explore the effects of MAO inhibition on nicotine-induced actions at the behavioral, biochemical and anatomical levels. The specific aims are: 1. To determine the selectivity requirements for MAO inhibitor enhancement of nicotine's reinforcing actions. We will use adult male and female rats to evaluate how the selectivity of MAO inhibitors affects the acquisition of nicotine self-administration; 2. To determine how MAO inhibition alters nicotine- induced changes in regional brain activity. We will use neuroanatomical and neurochemical approaches to evaluate the neural circuitry underlying the enhancement of nicotine reward by the MAO inhibitor, tranylcypromine; 3. To determine whether tranylcypromine selectively enhances nicotine reward as compared to other psychostimulants. We will compare the effect of tranylcypromine pretreatment on the acquisition of nicotine, cocaine and amphetamine self-administration. If selectivity for nicotine is observed, we will test whether MAO inhibition alters nicotine's relative reward strength in a 2-lever choice paradigm; 4. To determine if MAO inhibition increases nicotine withdrawal as a measure of dependence. Animals which are chronically infused with nicotine will be treated with saline or tranylcypromine and compared for mecamylamine- and naloxone-precipitated withdrawal symptoms and conditioned place aversion. The results of these studies should advance our understanding of the interaction of nicotine with other tobacco constituents, and lead to improved animal models of smoking that will strengthen our search for tobacco addiction's causes and cures.

虽然目前对吸烟原因的研究主要集中在尼古丁上，但这方面的研究正在积累