UCSF

Key PointsSignal transduction pathways that contribute to synaptic plasticity and to learning and memory processes are key mediators of neuroadaptations underlying the transition from moderate use of alcohol to excessive, uncontrolled alcohol seeking and drinking. These cascades are termed here as 'go pathways'.Endogenous signalling pathways gate the level of alcohol drinking and keep consumption in moderation. These 'stop pathways' also provide clues as to why some individuals become 'problem drinkers' and exhibit phenotypes of alcohol use disorder, whereas the majority of people do not. Excessive alcohol drinking and dependence occur when the stop pathways cease to function.Epigenetic mechanisms that control the conformation of chromatin as well as non-coding RNAs such as microRNAs change the molecular landscape in response to alcohol consumption and serve as molecular hubs that transduce both the go and stop pathways.Alcohol-induced neuroadaptations in the go and stop pathways produce brain region- and cell type-specific alterations, which in turn integrate into functional abnormalities in specific circuits. These molecular- to system-level functional alterations account for the behavioural phenotypes of addiction, such as the binge drinking of alcohol, compulsive alcohol seeking, dependence, negative affect, craving and relapse.