Cocaine-associated stimuli increase cocaine seeking and activate accumbens core neurons after abstinence.

Electrophysiological recordings were completed in rats (n = 14) trained to self-administer cocaine to determine whether activation of nucleus accumbens (Acb) neurons (core vs shell) by cocaine-associated stimuli is enhanced after 1 month of cocaine abstinence. After self-administration training, 170 cells were recorded during a single test session conducted either the next day or 1 month later. The test session consisted of three phases during which (1) the cocaine cue was presented unexpectedly to rats, (2) rats responded for the same cue in the absence of the drug (extinction), and (3) the cocaine cue was presented randomly between cocaine-reinforced responding during resumption of self-administration. The cocaine stimulus significantly increased activation of Acb core (not shell) neurons after 1 month of cocaine abstinence (compared with 1 d); this finding occurred regardless of contingency of cue presentation or cocaine availability. Acb core activation was not observed in other rats (n = 7) presented with the same stimulus never paired with cocaine. The results reflect a cellular neuroadaptation in the Acb core related to cocaine-associated cues that is observed during initial cue exposure and sustained during extinction and resumption of self-administration after prolonged drug abstinence.