Structured tracking of alcohol reinforcement (STAR) for basic and translational alcohol research

Abstract

There is inherent tension between methodologies developed to address basic research questions in model species and those intended for preclinical to clinical translation: basic investigations require flexibility of experimental design as hypotheses are rapidly tested and revised, whereas preclinical models emphasize standardized protocols and specific outcome measures. This dichotomy is particularly relevant in alcohol research, which spans a diverse range of basic sciences in addition to intensive efforts towards understanding the pathophysiology of alcohol use disorder (AUD). To advance these goals there is a great need for approaches that facilitate synergy across basic and translational areas of nonhuman alcohol research. In male and female mice, we establish a modular alcohol reinforcement paradigm: Structured Tracking of Alcohol Reinforcement (STAR). STAR provides a robust platform for quantitative assessment of AUD-relevant behavioral domains within a flexible framework that allows direct crosstalk between translational and mechanistically oriented studies. To achieve cross-study integration, despite disparate task parameters, a straightforward multivariate phenotyping analysis is used to classify subjects based on propensity for heightened alcohol consumption and insensitivity to punishment. Combining STAR with extant preclinical alcohol models, we delineate longitudinal phenotype dynamics and reveal putative neuro-biomarkers of heightened alcohol use vulnerability via neurochemical profiling of cortical and brainstem tissues. Together, STAR allows quantification of time-resolved biobehavioral processes essential for basic research questions simultaneous with longitudinal phenotyping of clinically relevant outcomes, thereby providing a framework to facilitate cohesion and translation in alcohol research.

Medial prefrontal dopamine dynamics reflect allocation of selective attention

“…Lick Microstructure: Microstructural analysis of lick behavior was conducted using custom MATLAB code as previously described 68,69 . A lick bout was defined as 3 licks within 1 second of each other with the first of the 3 licks representing the bout onset.…”

Non-Consummatory Behavior Signals Predict Aversion-Resistant Alcohol Drinking in Head-Fixed Mice

“…A standard method for modeling aversion-resistant drinking in rodents is to assess the degree to which an animal is willing to consume alcohol that is adulterated with the bitter tastant quinine [2][3][4][5][6], with the view that animals that are more willing to consume quinine adulterated alcohol are more aversion-resistant. This method of assessing ARD has been used in numerous animal models, including mice [6][7][8][9][10][11][12][13][14][15][16][17], Wistar rats [18][19][20][21][22][23][24], alcohol preferring P rats [18-20, 25, 26], and Sprague-Dawley rats [27].…”