Nico-teen: Mechanisms of Nicotine Reward and Withdrawal During Adolescence

Nico-teen：青春期尼古丁奖赏和戒断机制

• 批准号: 7623362
• 负责人: LAURA ELENA ODELL
• 金额: $ 5.92万
• 依托单位: UNIVERSITY OF TEXAS EL PASO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7623362
• 关键词: Adolescence; Adolescent; Adult; Age; Behavioral; Clinical Research; Data; Development; Disease; Dopamine; Equilibrium; Female; Female Adolescents; Glutamates; Goals; Knowledge; Lead; Long-Term Effects; Longitudinal Studies; Male Adolescents; Measures; Mecamylamine; Mediating; Microdialysis; Nicotine; Nicotine Withdrawal; Nicotinic Antagonists; Nucleus Accumbens; Pharmacological Treatment; Population; Positioning Attribute; Procedures; Public Policy; Rate; Rattus; Regulation; Relative (related person); Research; Research Personnel; Rewards; Risk; Role; Sex Characteristics; Smoker; Smoking; Smoking Behavior; System; Teenagers; Tobacco; Ventral Tegmental Area; Withdrawal; Work; adolescent smoking; base; gamma-Aminobutyric Acid; health economics; in vivo; innovation; men' s group; neurochemistry; neuromechanism; neuronal cell body; preference; programs; sex; skills; smoking cessation; tobacco abuse; transmission process

Tobacco abuse among adolescents is a major health and economic concern, yet there is a critical knowledge gap regarding the mechanisms that mediate adolescent smoking behavior. Our preliminary data demonstrate that adolescent male rats display enhanced nicotine reward and reduced nicotinewithdrawal relative to adults. This proposal extends our previous work by examining the neural mechanisms that mediate developmental sensitivity and sex differences in the behavioral .effects of nicotine reward and withdrawal. In order to study the long-term consequences produced by adolescent nicotine exposure, our proposal also includes adult rats pre-exposed to nicotine during adolescence. Nicotine reward is mediated in part by enhanced dopamine (DA) transmission in the nucleus accumbens (NAcc). In contrast, nicotine withdrawal produces a decrease in NAcc DA levels. Changes in NAcc DA transmission are mediated by excitatory and inhibitory systems that regulate DA projections that originate in the ventral tegmental area (VTA). During adolescence, excitatory systems that regulate DA are overdeveloped, whereas inhibitory systems are underdeveloped. We hypothesize that adolescents will display enhanced nicotine reward and reduced nicotine withdrawal relative to adults. These developmental differences are likely mediated via enhanced excitation and reduced inhibition of VTA DA cell bodies. Overall we expect that these differences will be magnified in female adolescents and nicotine pre-exposed rats. This is based on clinical studies demonstrating that teenage females and adults pre-exposed to nicotine during adolescence display enhanced vulnerability to long-term tobacco abuse. Behavioral studies will compare nicotine reward using place preference procedures and nicotine withdrawal using place aversion procedures. Neurochemical studies will employ in vivo microdialysis procedures to compare NAcc DA and concomitant measures of excitatory and inhibitory systems in the VTA following nicotine administration and during nicotine withdrawal. This research is significant because our findings may have significant implications towards guiding public policies regarding tobacco regulation and warnings directed at teenagers and females. Further, a better understanding of the mechanisms mediating adolescent tobacco abuse will lead to more effective treatments for young smokers who are most at risk of developing diseases caused by long-term smoking.

青少年中的烟草滥用是一个主要的健康和经济问题，然而， 关于青少年吸烟行为的中介机制的知识差距。我们的初步数据 表明青春期雄性大鼠表现出增强的尼古丁奖赏和减少的尼古丁戒断 相对于成年人。这项建议扩展了我们以前的工作，通过检查神经机制， 调节尼古丁奖赏对行为的影响， 戒断为了研究青少年尼古丁暴露产生的长期后果， 该提案还包括在青春期预先暴露于尼古丁的成年大鼠。尼古丁奖赏是通过 部分通过增强多巴胺（DA）在丘脑核（NAcc）的传递。相反，尼古丁 戒断导致NAcc DA水平降低。NAcc DA传递的变化由以下因素介导： 调节起源于腹侧被盖区的DA投射的兴奋和抑制系统 （VTA）。在青春期，调节DA的兴奋性系统过度发育，而抑制性系统过度发育。 系统不发达。我们假设青少年会表现出更强的尼古丁奖赏， 与成人相比，尼古丁戒断率降低。这些发育差异可能通过以下途径介导： 增强VTA DA细胞体的兴奋和减少抑制。总的来说，我们预计这些差异 将在雌性青少年和尼古丁预暴露大鼠中放大。这是基于临床研究 表明青少年女性和成年人在青春期暴露于尼古丁， 更易受到长期烟草滥用的影响。行为研究将比较尼古丁奖励使用 位置偏好程序和使用位置厌恶程序的尼古丁戒断。神经化学 研究将采用体内微透析程序来比较NAcc DA和伴随的 尼古丁给药后和尼古丁戒断期间腹侧被盖区的兴奋和抑制系统。 这项研究意义重大，因为我们的发现可能对指导公众 针对青少年和女性的烟草管制和警告政策。此外，更好的 了解青少年烟草滥用的调节机制将导致更有效的治疗 针对年轻吸烟者，他们最有可能患上因长期吸烟而引起的疾病。