Vanderbilt AUD Research and Education Center (VAREC)

ABSTRACT The central thesis of the Vanderbilt AUD Research and Education Center (VAREC) is that effective treatment requires recognition of, and deep understanding of the diverse symptoms, etiologies, and disease progressions that underlie what is unitarily referred to as Alcohol Use Disorder (AUD). We propose a reverse translational

“precision neuroscience” approach. We will dissect AUD endophenotypes to generate human circuit construct validated animal models that we will utilize to gain mechanistic insights and test therapeutic targets. VAREC will consist of 4 research components (Projects1-4) supported by Administrative and Research cores, as well

as a Dissemination core. Project 1 (Blackford) expands our initial human imaging studies into a deep sampling approach to analyze BNST and network connectivity in AUD across the abstinence timespan, exploring individual differences in these networks with AUD relevant domains such as anxiety and depression. Project 2

(Winder) will build off an already active collaboration with Project 1 to perform reverse translational mouse studies to test emergent hypotheses on insula-BNST and hippocampal-BNST connectivity in mouse models of AUD, and to explore potential time-dependent therapeutic approaches during abstinence. Project 2 will also

perform specific broad-scale mouse brain imaging studies to define network nodes for Project 1 to explore in years 4-5. Project 3 (Calipari) will explore whether alterations in negative affect observed in Project 1 and Project 2 lead directly to functional enhancement of negative reinforcement-oriented circuitries and behavior.

Finally, Project 4 (Siciliano) will engage in deep phenotyping of individual differences in mouse behaviors correlated with compulsive drinking behavior, working across the projects to identify populations of precise behaviors that are predictive of compulsive ethanol seeking. Projects 2 and 4 explore therapeutic targets

through analysis of endocannabinoid and dynorphin signaling. The project interactions will be coordinated by an Administrative core. A Research core will provide mice that have undergone one of two voluntary alcohol exposure models, Chronic Drinking-Forced Abstinence (CDFA) or Structured Tracking of Alcohol

Reinforcement (STAR). It will also provide research infrastructure and computational support. Through a Dissemination core, VAREC will play an important role in public health by activities aimed at destigmatizing AUD treatment seeking and increasing prevention through novel near-peer targeting of adolescents. This core

will also allow VAREC to serve as a resource to the alcohol research community to facilitate mainstream incorporation of cutting-edge tools into the field.