Neuroimaging methodologies have become increasingly important tools in neuroscience research, providing a means for understanding the neural substrates related to drug action. This K01 Award will provide support and protected time for Dr. Stephen Kohut to obtain additional experience and mentoring that will complement and expand his existing expertise in preclinical IV drug self-administration and medication testing by acquiring new skills in pharmacologic magnetic resonance imaging (phMRI). During the proposed award period the PI will first complete an intensive training program to develop the core skills and knowledge necessary to design, conduct, and analyze phMRI studies. Training will occur at the McLean Imaging Center and Massachusetts General Hospital and will involve coursework and seminars, and discussions and meetings with a world-renowned mentoring team that will facilitate completion of an innovative research project. A major strength of the research project is that it will optimize the PI's training experience through a systematic series f experiments evaluating neuronal function during the phases of drug addiction typically modeled in the laboratory including IV self-administration (i.e., drug-taking) and reinstatement (i.e., relapse) and the effects of novel treatment approaches (pharmacological and/or behavioral) in non-human primates (NHP). Another major strength of the research plan, which will have a major impact on the field, is that it involves the use of awake, behaving NHP to study the functional consequences of nicotine self-administration and reinstatement and how they are altered during treatment. Functional brain activity in multiple brain regions will be directly relaed to ongoing real time behavior that can be measured within and across behavioral sessions. Focused research training in phMRI will occur at 3 Tesla (3T) through the Research Plan, but the PI will also receive training on a state-of-the-art, ultra-high field 9.4T magnet, large enough to accommodate NHP. The combination of training at clinical field strength (3T) coupled with training at ultra-high field strength (9.4T) will equip the Candidate with the knowledge and skills necessary to become an R01-funded independent investigator at the forefront of truly translational addiction research relating behavior and brain function. Overall, this training experience will allow the Candidate to develop a novel investigative approach for examining how novel treatments influence the various neuronal effects of nicotine and other drugs of abuse during periods of drug-taking and relapse, and will establish the PI as an independent scientist who is qualified to conduct highly translational addiction research that will address the need for highly trained investigators who can explore the neural correlates of drug abuse and addiction.
Nicotine addiction is recognized as the largest cause of preventable death in the United States (e.g., ~480,000 deaths/year) suggesting an urgent need for more effective medications and treatment strategies. This project is designed to systematically provide the PI with intensive, supervised research training in pharmacologic magnetic resonance imaging (phMRI) in preparation for an independent research career in translational models of drug abuse and addiction investigating the neural correlates of drug effects on behavior. The proposed research will provide a novel perspective on the neurobiology of nicotine addiction by utilizing phMRI analysis in awake, behaving nonhuman primates that will aid in the development of more effective treatment strategies to facilitate smoking cessation.
