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However, the striatal cellular mechanisms through which extinction alters later alcohol seeking remain unclear. Using a mouse model of operant alcohol self\u2010administration, we examined two distinct direct\u2010pathway medium spiny neuron (dMSN) populations in the dorsomedial striatum. Extinction reduced cue\u2010induced alcohol seeking and decreased the probability that acquisition\u2010recruited dMSNs were reactivated during relapse testing. Chemogenetically maintaining activity in acquisition\u2010recruited dMSNs during extinction slowed the reduction in alcohol\u2010seeking and enhanced subsequent relapse. In contrast, increasing activity in \u03bc\u2010opioid receptor (MOR)\u2010expressing dMSNs, a striosome\u2010enriched population, accelerated the reduction in responding and decreased later relapse without altering inactive\u2010lever responding or locomotor activity. 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