Functional magnetic resonance imaging (fMRI) of the brain has improved our understanding of drugs of abuse. Progress in applying this approach to conscious animals has been slow because subjects must be immobile during imaging. We have invented a device that allows us to image rodents while awake, opening new opportunities to study brain function non-invasively over time. Repeated exposure to drugs of abuse evokes a progressive increase in locomotor stimulation, termed behavioral sensitization. It is thought that sensitization is central to addiction to drugs, including nicotine. This resubmission addresses two potentially important observations about nicotine sensitization. First, it can be imaged with fMRI, allowing identification of the brain structures involved. The role of individual neurotransmitters in sensitization can be evaluated through the administration of selected receptor agonists to sensitized animals during imaging. Our preliminary data indicate that fMRI can be used to determine the role in sensitization to glutamate receptors in various brain regions.
The aims of this proposal are 1) to determine if the administration of nicotine to sensitized animals produces alterations in neuronal activity in the ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus, ventral pallidum, anterior cingulate gyrus, septum and visual cortex as measured by blood oxygen level-dependent contrast (BOLD);2) to determine how long nicotine sensitization persists;3) to determine how the administration of monoamine oxidase inhibitors in conjunction with nicotine alters the persistence of sensitization;and 4) to investigate the role of glutamate in the expression of sensitization. This proposal is highly innovative in the use of fMRI to study sensitization. Once developed, this technique could be used to translate our knowledge of sensitization in animals to the study of sensitization in humans and its relation to addiction. The imaging of sensitization may provide a powerful new tool for the exploration of novel pharmacologic approaches to treating nicotine addiction, which is the largest contributor to preventable mortality in the developed world.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (02))
Program Officer
Aigner, Thomas G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Massachusetts Medical School Worcester
Schools of Medicine
United States
Zip Code
Thompson, Matthew F; Poirier, Guillaume L; Dávila-García, Martha I et al. (2017) Menthol enhances nicotine-induced locomotor sensitization and in vivo functional connectivity in adolescence. J Psychopharmacol :269881117719265
Poirier, G L; Huang, W; Tam, K et al. (2017) Awake whole-brain functional connectivity alterations in the adolescent spontaneously hypertensive rat feature visual streams and striatal networks. Brain Struct Funct 222:1673-1683
Lee, Athene K W; Gansler, David A; Zhang, Nanyin et al. (2017) Relationship of mindful awareness to neural processing of angry faces and impact of mindfulness training: A pilot investigation. Psychiatry Res 264:22-28
Huang, Wei; Tam, Kelly; Fernando, Janaque et al. (2015) Nicotine and Resting-State Functional Connectivity: Effects of Intermittent Doses. Nicotine Tob Res 17:1311-7
Liang, Zhifeng; King, Jean; Zhang, Nanyin (2012) Intrinsic organization of the anesthetized brain. J Neurosci 32:10183-91
Fulwiler, Carl E; King, Jean A; Zhang, Nanyin (2012) Amygdala-orbitofrontal resting-state functional connectivity is associated with trait anger. Neuroreport 23:606-10
Liang, Zhifeng; King, Jean; Zhang, Nanyin (2012) Anticorrelated resting-state functional connectivity in awake rat brain. Neuroimage 59:1190-9
Liang, Zhifeng; King, Jean; Zhang, Nanyin (2011) Uncovering intrinsic connectional architecture of functional networks in awake rat brain. J Neurosci 31:3776-83
King, Jean; Huang, Wei; Chen, Wei et al. (2011) A comparison of brain and behavioral effects of varenicline and nicotine in rats. Behav Brain Res 223:42-7
Zhang, Nanyin; Rane, Pallavi; Huang, Wei et al. (2010) Mapping resting-state brain networks in conscious animals. J Neurosci Methods 189:186-96

Showing the most recent 10 out of 11 publications