PILOT STUDY--CNS VIRAL INJURY AND VULNERABILITY TO NICOTINE ABUSE

尼古丁滥用问题对我们社会和医疗保健系统的严重性强调了研究工作的重要性，以了解尼古丁使用和滥用的生物学。越来越多的实验证据支持重复刺激中脑边缘多巴胺神经元在尼古丁依赖的发展和维持中的作用。事实上，尼古丁对大脑儿茶酚胺系统的影响被认为是尼古丁最重要的中枢神经系统作用之一。使用基于Boma病病毒-BDV（精神分裂症的动物模型）的病毒诱导的中皮质边缘DA -过度活跃的小动物模型，所提出的实验将探索由持续CNS病毒感染引起的DA过度活跃的非损伤动物模型与药物寻求行为之间的关系。将开发动物模型，然后检测尼古丁的依赖诱导效应（通过尼古丁戒断的躯体体征测量）和尼古丁戒断的情感（情绪）效应（通过位置厌恶测量）（具体目标1）。关于脑炎病毒感染如何产生多巴胺能障碍影响尼古丁依赖的知识可以为尼古丁依赖的机制提供新的见解，并有助于了解尼古丁滥用和神经精神疾病的共同发病率。

The magnitude of the problem of nicotine abuse to our society and our health care delivery system underscores the importance of research efforts to understand the biology of nicotine use and abuse. There is increasing experimental evidence to support a role for repeated stimulation of the - mesolimbic dopamine neurons in the development and maintenance of nicotine dependence. In fact, the effects of nicotine on brain catecholamine systems are thought to be among nicotine's most important CNS actions. Using a small animal model of viral-induced mesocorticolimbic DA - hyperactivity based on Boma Disease Virus-BDV (an animal model of schizophrenia), the proposed experiment will explore the relation between a non-lesion animal model of DA hyperactivity, caused by persistent CNS viral infection, and drug-seeking behavior. The animal model will be developed then tested for the dependence-inducing effects of nicotine, as measured by the somatic signs of nicotine withdrawal, and the affective (emotional) effects of nicotine withdrawal, as measured by place aversion (Specific Aim 1). Knowledge of how an encephalitic viral infection producing dopaminergic disturbances influences nicotine dependence could provide new insights into mechanisms of nicotine dependence, and aid in understanding the co-morbidity of nicotine abuse and neuropsychiatric conditions.