Authors
Rude, A., Hayek, N., Lapish, C., Kuznetsov, A.
Abstract
Binge drinking is characterized by an initial bout of rapid, high-vigor alcohol intake (front-loading) followed by a prolonged period of lower-rate "maintenance" drinking, yet the circuit mechanisms that generate and regulate these phases remain unclear. Here, we develop a systems-level computational model that links the structure of binge drinking to interactions among medial prefrontal cortex (mPFC), insula, striatum, and ventral tegmental area (VTA). The model consists of cortical Seek (mPFC) and Go (insula) populations that form a mutually excitatory loop, a SetPoint population that integrates striatal activity as an internal estimate of effort/consumption, ventral (nucleus accumbens, NAc) and dorsal (dorsolateral striatum, DLS) striatal populations, and a dopaminergic VTA population providing transient reward-prediction signaling. Using a firing-rate formalism with noisy dynamics, we reproduce the canonical two-phase binge pattern and show that: (i) the PFC-insula loop acts as a bistable module that initiates and sustains front-loading; (ii) striato-cortical feedback to the Setpoint population controls the timing of the transition from front-loading to maintenance without altering its vigor; and (iii) the amplitude of the VTA dopamine transient selectively scales front-loading intensity. Sensitivity analyses identify PFC-insula connectivity, VTA-to-NAc modulation, and striato-cortical feedback as key parameters that bifurcate two-phase drinking into regimes with abolished or persistent front-loading. These findings provide a mechanistic framework for interpreting binge-like alcohol intake in terms of identifiable circuit motifs and generate testable predictions for targeting mPFC-insula-striatal-VTA interactions in alcohol use disorder.
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bioRxiv
The authors list and abstract were imported from bioRxiv on 03 Oct 2026.
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