The mesolimbic dopamine signatures of relapse to alcohol-seeking

The mesolimbic dopamine system comprises distinct compartments supporting different functions in learning and motivation. Less well understood is how complex addiction-related behaviors emerge from activity patterns across these compartments. Here we show how different forms of relapse to alcohol-seeking are assembled from activity across the ventral tegmental area and the nucleus accumbens. Using gCaMP and dLight fibre photometry, we show that self-administration and two forms of relapse (renewal/context-induced reinstatement and reacquisition) are associated with recruitment across the mesolimbic dopamine system. Using a variety of interventions, we show that this activity is causal to both forms of relapse. Finally, we use dissimilarity matrices to identify mesolimbic dopamine signatures of self-administration, extinction, and relapse. We show that signatures of relapse can be identified from heterogeneous activity profiles across the mesolimbic dopamine system and that these signatures differ for different forms of relapse.