Nature
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Nucleus accumbens neurons serve to integrate information from cortical and limbic regions to direct behaviour. Addictive drugs are proposed to hijack this system, enabling drug-associated cues to trigger relapse to drug seeking. However, the connections affected and proof of causality remain to be established. ⋯ Optogenetic reversal of cocaine-evoked plasticity at both inputs abolishes seeking, whereas selective reversal at mPFC or ventral hippocampus synapses impairs response discrimination or reduces response vigour during seeking, respectively. Taken together, we describe how information integration in the nucleus accumbens is commandeered by cocaine at discrete synapses to allow relapse. Our approach holds promise for identifying synaptic causalities in other behavioural disorders.