Figure 4. A contemporary overview of the neurobiology of alcohol use disorders.

A∣ Acute direct and indirect neuropharmacological effects of alcohol, including antagonism of glutamatergic neurons and agonism of both GABAergic neurons and opioidergic neurons. Of note, in addition to agonism of opioidergic neurons in the nucleus accumbens (NAcc), endogenous opioid release in the ventral tegmental area (VTA) leads to an inhibitory effect on GABAergic neurons that in turn increases dopamine release in the NAcc. B∣ Progressive transition from positively reinforcing (rewarding) effects to negatively reinforcing (relieving) effects. C∣ a theorized sequence and associated deficits in the progression to AUDs. D∣ The putative neurocircuitry associated with each feature of the cycle.

Notes: EtOH = alcohol (ethanol); [binge/intoxication] DS = dorsal striatum, VS = ventral striatum, GP = globus pallidus, Thal = thalamus; [affect/withdrawal] BNST = bed nucleus of the striatum, CeA = central nucleus of the amgygdala; [preoccupation/ anticipation] ACC = anterior cingulate cortex, dlPFC = dorsolateral prefrontal cortex, vlPFC = ventrolateral prefrontal cortex, vmPFC = ventromedial prefrontal cortex, OFC = orbitofrontal cortex. HPC = hippocampus, Source” Volkow et al. OUD NRDP]. Figures 4c and 4d adapted with permission from Refs 397 and 398.

please refer to Figure 4 of MacKillop, J., Agabio, R., Feldstein Ewing, S.W. et al. Hazardous drinking and alcohol use disorders. Nat Rev Dis Primers 8, 80 (2022).