Fig. 1: Diagram of experimental design and rationale.

A Rhesus macaques (17 alcohol and 11 calorically yoked or housing controls) underwent a drinking (or housing control) protocol designed to uncover individual differences in drinking phenotypes between subjects. Briefly, a schedule induced polydipsia procedure was used to induce voluntary alcohol consumption, followed by 12 months of 22 hour/day open access drinking, a month of forced abstinence, 3 months of open access alcohol reintroduction, a month of forced abstinence, 3 months of open access alcohol reintroduction, and one month of forced abstinence at the end of which subjects were necropsied. B–E Drinking data from each epoch of the self-administration paradigm is shown, with color indicating the same subject throughout. B Cumulative alcohol intake was calculated over the first period of open access. C Average daily alcohol intake during each of the two alcohol reintroduction periods. D Lifetime intake in g/kg was calculated for each of the 17 alcohol-exposed subjects. E Blood alcohol concentration (in milligram percent [i.e. mg/dL]) was collected weekly, 7 hours after session start, for each subject and was strongly positively associated with the alcohol intake on the same day (two-tailed Pearson’s correlation). F After necropsy, the brain was blocked in coronal sections including the nucleus accumbens (NAc) core and the ventral tegmental area (VTA); dopamine dynamics were recorded from the NAc with fast-scan cyclic voltammetry, and gene expression from the upstream VTA region was assessed via bulk RNA-seq. Stimulation parameters and pharmacological manipulations were used to assess different features of dopamine terminal release in the NAc. These effects were then correlated with gene expression measures from the VTA to assess the relationship between terminal function and upstream transcription. Unless otherwise indicated, values indicate mean ± SEM. (drinkers: n = 17) Created in BioRender. Siciliano, C. (2025) https://BioRender.com/l92m987.