Different neural substrates mediate cocaine seeking after abstinence versus extinction training: a critical role for the dorsolateral caudate-putamen.

Cue-induced reinstatement of extinguished drug seeking is a preclinical model of relapse. However, relapse typically occurs after abstinence rather than explicit extinction training. We show that inactivation of the dorsolateral caudate-putamen, but not other structures previously implicated in reinstatement, attenuates cocaine seeking after abstinence. This suggests that there is limited overlap in the substrates of cocaine seeking after abstinence versus extinction, and that habit learning exerts greater control over drug seeking than regions implicated in stimulus-reward associations.