Nicotine amplification of behavioral and neural responses to alcohol cues

 描述（由申请人提供）：尼古丁和酒精是最常滥用的娱乐性药物，尼古丁依赖和酒精中毒具有高度的共病性。例如，估计90%的酗酒者也吸烟，估计60%的吸烟者酗酒。酒精和尼古丁滥用的健康后果是严重的，包括许多类型的癌症，心血管疾病，肝损伤和慢性阻塞性肺病。此外，这些健康问题在共同滥用这些药物的个体中更为严重。因此，了解尼古丁和酒精滥用之间相互作用的行为和神经生物学机制至关重要。这些信息可以用于开发专门针对这些药物成瘾的并发症的治疗方法。尼古丁成瘾和酒精中毒的一个主要问题是个体对与饮酒和吸烟相关的人、地点和其他线索的高度反应性引起的渴望和复发。此外，与吸烟相关的暗示也会引发饮酒。初步研究表明，尼古丁增强了酒精相关线索的反应，但不知道尼古丁对饮酒的影响是否是次要的。此外，对许多药物相关线索的反应涉及大脑的动机回路，包括以互补方式影响行为的前额叶皮层和前额叶皮层。尼古丁可能是通过激活这一系统来增加对酒精提示的反应，但迄今为止还没有研究探讨过这种可能性。这项研究将确定尼古丁是否通过增加该系统对酒精提示的反应来增加酒精摄入量，以及对酒精提示的反应是否取决于大脑激励回路中的特定子回路。该项目将确定尼古丁增加大鼠饮酒能力的行为和神经基础，通过分离饮酒特定阶段的线索影响，并通过测量和操纵大脑激励电路的神经元活动。为此，两组实验将确定1）饮酒的哪些特定方面（包括对酒精线索的反应）受到尼古丁的影响，以及2）哪些特定的投射是必要的，足以产生具有激励价值的酒精线索。该项目关于尼古丁和酒精之间相互作用的特定行为和神经点的研究结果将允许开发专门针对尼古丁对酒精摄入影响的实验和药理干预措施。

 DESCRIPTION (provided by applicant): Nicotine and alcohol are the most commonly abused recreational drugs, and nicotine dependence and alcoholism have a high degree of comorbidity. For example, an estimated 90% of alcoholics also smoke, and an estimated 60% of smokers engage in binge drinking. The health consequences of alcohol and nicotine abuse are severe, including many types of cancer, cardiovascular disease, liver damage, and chronic obstructive pulmonary disease. Further, these health issues are more severe in individuals who co-abuse these drugs. Therefore, it is crucial to understand the behavioral and neurobiological mechanisms that underlie the interaction between nicotine and alcohol abuse. This information can then be used to develop treatments specifically designed address the comorbidity of addiction to these drugs. A major problem with both nicotine addiction and alcoholism is the craving and relapse induced by individuals' heightened responsivity to the people, places, and other cues associated with drinking and smoking. In addition, smoking-associated cues can trigger drinking. Preliminary studies demonstrate that nicotine enhances the response alcohol-associated cues, but it is not known whether nicotine's effects on alcohol drinking are secondary to these effects. In addition, the response to many drug-associated cues involves the brain's motivational circuit, including the nucleus accumbens and the prefrontal cortex, which affect behavior in complementary ways. It may be through activation of this system that nicotine increases the response to alcohol cues, but to date no studies have examined this possibility. The proposed work will determine whether nicotine increases alcohol intake by increasing the response to alcohol cues within this system, and whether the response to alcohol cues depends upon specific subcircuits within the brain's motivational circuitry. This project will determine th behavioral and neural basis for the ability of nicotine to increase alcohol drinking in rats, by dissociating the effects of cues during specific phases of alcohol drinking, and by measuring and manipulating the activity of neurons with the brain's motivational circuitry. To this end, two sets of experiments will determine 1) which specific aspect of alcohol drinking (including the response to alcohol cues) are affected by nicotine, and 2) which specific projections are necessary and sufficient to engender alcohol cues with motivational value. Findings from this project regarding the specific behavioral and neural points of interaction between nicotine and alcohol will allow for the development of experimental and pharmacological interventions that specifically address the effect of nicotine on alcohol intake.