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Adolescent Rodent fMRI Model of Nicotine Dependence

Principal Investigator: Elliot Stein and Kia Jackson

Funding Mechanism: Interagency Agreement

ID number: 224-15-9004

Award Date: 12/9/2014

Institution: National Institutes of Health - Contract


A cingulate-striatal addiction circuit, a neurological connection in the brain that has been identified in humans who are addicted to tobacco (but not in tobacco users who are not addicted), has been developed for use as a rodent model of nicotine addiction. This project extends the pilot study that established this circuit in rodents by examining factors that could alter the development of addiction. The circuit will be evaluated using resting state functional connectivity MRI, an imaging technique that measures brain activity while the subject is not engaging in any particular task or activity.  Since adolescence is the time of susceptibility to developing nicotine addiction, this project will examine the developmental trajectory of the circuit as a biomarker of nicotine addiction in adult versus adolescent rats. The impact of nicotine dose, age, and time course of nicotine exposure on circuit development and strength will be examined and analyzed in relation to the withdrawal/extinction time course. Specific aims are: 1) to compare the dose response range of nicotine exposure that elicits enhanced nicotine dependence in adolescent versus adult rats; 2) to identify the circuit strength associated with increased behavioral measures of nicotine dependence following adolescent rat nicotine exposure; and 3) to identify adolescent rat brain structure changes associated with enhanced behavioral measures of nicotine dependence.  As a biomarker of addiction, this circuit may subsequently be used to investigate the abuse liability of various tobacco products and constituents, which could inform future regulatory activities.