PROJECT SUMMARY/ABSTRACT
This K99/R00 NIH Pathway to Independence Award will provide Dr. Cofresí, trained as a preclinical
neuroscientist, with a two-year intensive, mentored training and research experience in translational
neuroscience and three-years of research support that will launch his career as an independent investigator.
The training and research program focuses on bidirectional translation between preclinical and human
laboratory models of neurobehavioral mechanisms that promote alcohol use disorder (AUD). The K99 career
development plan will provide training in AUD psychopathology, human alcohol administration, human
cognitive/affective neuroscience, and human functional neuroimaging methods. Training will include
coursework, conferences, individualized one-on-one mentoring, seminars, and workshops. The K99 research
focuses on a neurobehavioral domain of the Addictions Neuroclinical Assessment believed to be critical to the
Addiction/AUD Cycle: the attribution of incentive salience (IS) to alcohol cues. Preclinical and human
neurobehavioral evidence suggests that repeated alcohol intoxication can sensitize IS attribution to alcohol
cues, which may drive the Addiction/AUD Cycle in some individuals. To begin testing this possibility, Dr.
Cofresí will translate a preclinical model of individual differences in propensity to attribute IS to reward-
predictive cues into a human laboratory model of individual differences in propensity to attribute IS to alcohol
intoxication-predictive vs. natural reward-predictive cues, and examine how these individual differences are
associated with future problematic alcohol use. Dr. Cofresí’s development will be facilitated by a team with
collective expertise spanning the areas of training (Drs. Bruce Bartholow, Shelly Flagel, Brett Froeliger, David
Kareken, Denis McCarthy, Ed Merkle, Thomas Piasecki, Kenneth Sher, Todd Schachtman). The K99 phase
will take place at the University of Missouri, a world-class research institution, in the Department of
Psychological Sciences, home to renowned faculty in alcohol and addiction research with human participants
and a premier alcohol research training program (T32-AA013526). The R00 research will take place at a to-be-
determined R1 institution, and will focus on continued testing of IS attribution to alcohol-predictive cues and its
sensitization in the human laboratory. This K99/R00 award will produce research that advances Goal 1
Objective 1a of the 2017-2021 NIAAA Strategic Plan, which involves identifying behavioral and neurobiological
mechanisms underlying AUD, and explaining heterogeneity in how people progress through the Addiction/AUD
Cycle, in order to inform the development of AUD prevention and treatment. This K99/R00 award will also
produce an independent scientist able and committed to conducting basic behavioral and neurobiological
research with human participants that will continue to advance NIAAA’s mission to improve diagnosis,
prevention, and treatment of alcohol-related problems, including AUD.
