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.
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