The following studies are proposed for the first two years of CTNA funding:
Human Alcohol Habits; Behavioral and Brain Mechanisms
- Pilot 1 Principal Investigator: Dr. Dana Small.
This projects hopes to provide a neural and behavioral characterization of instrumental learning for alcohol and sucrose reinforcers in humans. This work will directly complement that of the preclinical lab (Project 1 - PI: Dr. Taylor) and the clinical investigations of Pavlovian-to-Instrumental Transfer (PIT) using functional neuroimaging (Project 3 - PI: Dr. Pearlson), since PIT is believed to be one process through which goals cede control of behavior to habits. Ultimately, alcohol use habits are the final therapeutic target of the CTNA – it is therefore essential that we develop a means to characterize and quantify them in humans.
Attention, Learning and Addiction: An Eye-Tracking Approach
- Pilot 2 Principal Investigator: Dr. Philip Corlett.
We hope to provide a consilient explanation for the role of salient drug predicting cues in alcoholism, bridging physiological and clinical risk with formal learning theory. This work will directly complement that of the preclinical lab (Project 1 - PI: Dr. Taylor) and the clinical investigations of Pavlovian-to-Instrumental Transfer using functional neuroimaging (Project 3 - PI: Dr. Pearlson), as well as the therapeutics studies using cue-induced craving as independent measures (Project 2 - PI: Drs. Abi-Dargham & Petrakis and Project 4 - PI: Dr. Krishnan-Sarin). New cognitive therapies may be inspired by our enhanced understanding of learning and attention in addiction. Potential pharmacotherapies may be developed more rapidly and with more disease relevance in the animal models of addiction that we hope to optimize on the basis of our results. Finally, if successful, this project proffers the exciting possibility of developing bespoke treatment approaches tailored to individuals based on behavioral assessments of Pavlovian learning and attention.
Imaging Cortical Dopamine Release in Alcoholism
- Pilot 3 Principal Investigator: Dr. Anissa Abi-Dargham.
This project provides an important test of key CTNA hypotheses related to the role of cortical dopamine systems in alcoholism. We hypothesize that a deficit in prefrontal cortical dopamine release would “lock in” alcohol-related habits. This hypothesis is supported by our prior report of a ventral striatal dopamine deficit and the fact that the orbito-frontal cortex and the ventral striatum receive dopamine projections from very close afferents in the ventral tegmental area. We will obtain initial information in this regard that will define future directions of the Center and that will be valuable for the field in general as no information is currently available regarding cortical dopamine transmission in alcoholism, despite the involvement of dopamine in this disease and the alterations in orbito-frontal function previously demonstrated in patients and subjects with a family history of alcoholism.