Nicotine & Ethanol Influences on Contextual Conditioning

描述（由申请人提供）：许多研究表明酒精和尼古丁的使用是相关的。此外，研究还表明，吸烟是青少年从社交饮酒过渡到问题饮酒的一个强有力的预测因素。然而，酒精和尼古丁通常一起使用的原因并不完全清楚，可能涉及多种因素。酒精与尼古丁的共同使用可能是有吸引力的，因为在饮酒期间使用尼古丁可能会减少酒精的一些负面影响，如认知障碍。海马体是一种参与学习的结构，似乎对乙醇的破坏性影响特别敏感。例如，学习一个事件的背景，一个依赖于海马体的任务，被大鼠和小鼠的乙醇给药所破坏。然而，初步研究结果表明，尼古丁可以逆转这种赤字。因此，尼古丁减少乙醇负面影响的能力可能会促进更多或重复的酒精消费。这可能会促进饮酒模式的转变。此外，反复使用尼古丁也可能导致尼古丁成瘾。这是该提议的一个假设，即尼古丁将防止C57 BL/6小鼠中乙醇诱导的背景条件反射缺陷，并且海马是尼古丁通过改变乙醇破坏的细胞过程来减少乙醇相关学习缺陷的神经部位。作为研究尼古丁对酒精使用的交互作用的第一步，该提案将研究乙醇和尼古丁联合给药对酒精依赖性学习的影响，并研究支持乙醇-尼古丁相互作用的神经生物学。了解尼古丁和乙醇共同使用的原因将有助于了解影响饮酒模式和尼古丁使用变化的因素。了解潜在的神经生物学不仅有助于进一步理解这一点，而且有助于开发酒精中毒和尼古丁成瘾的治疗方法。

DESCRIPTION (provided by applicant): Numerous studies have shown alcohol and nicotine use are correlated. Further, it has also been shown that smoking is a strong predictor for transitioning from social to problem drinking in adolescents. The reasons why alcohol and nicotine are commonly used together, however, are not completely understood and may involve multiple factors. It is possible that the co-use of alcohol with nicotine may be appealing because nicotine use during alcohol consumption may decrease some of the negative effects of alcohol such as disrupted cognition. The hippocampus is one structure involved in learning that seems particularly sensitive to the disruptive effects of ethanol. For instance, learning the context of an event, a task that is dependent on the hippocampus, is disrupted by ethanol administration in rats and mice. Preliminary findings, however, suggest that nicotine can reverse this deficit. Thus, this ability of nicotine to reduce negative effects of ethanol could facilitate greater or repeated alcohol consumption. This could facilitate a transition in drinking patterns. In addition, repeated nicotine use could also lead to nicotine addiction. It is a hypothesis of this proposal that nicotine will prevent ethanol-induced deficits in contextual conditioning in C57BL/6 mice and that the hippocampus is a neural site were nicotine works to reduce ethanol-associated learning deficits by altering the cellular processes disrupted by ethanol. As an initial step in investigating the interactive effects of nicotine on alcohol use, this proposal will examine the effects of ethanol and nicotine co-administration on hippocampus-dependent learning and also examine the neurobiology that supports ethanol-nicotine interaction. Understanding why nicotine and ethanol are co-used will aid in understanding factors that influence shifts in drinking patterns and nicotine use. Understanding the underlying neurobiology will not only further aid in this understanding but will also aid in developing treatments for alcoholism and nicotine addiction.