Upregulation of Arc mRNA expression in the prefrontal cortex following cue-induced reinstatement of extinguished cocaine-seeking behavior.

Cocaine-associated cues acquire incentive motivational effects that manifest as cue-elicited craving in humans and cocaine-seeking behavior in rats. Here we examine the hypothesis that neuronal processes associated with incentive motivational effects of cocaine cues involve increased expression of the plasticity-associated gene, Arc. Rats trained to self-administer cocaine subsequently underwent extinction training, during which cocaine-seeking behavior (i.e., responses without cocaine reinforcement) progressively decreased. Rats were then tested for cocaine-seeking behavior either with or without response-contingent presentations of light/tone cues that had been previously paired with cocaine infusions during self-administration training. Cues elicited reinstatement of cocaine-seeking behavior and were accompanied by increased Arc mRNA levels in the orbitofrontal, prelimbic, and anterior cingulate cortices, suggesting Arc involvement in conditioned plasticity associated with incentive motivational effects of cocaine cues. Additionally, rats with a history of cocaine self-administration and extinction exhibited upregulation of Arc expression in several limbic and cortical regions relative to saline-yoked controls regardless of cue exposure condition, suggesting persistent neuroadaptations involving Arc within these regions. (c) 2008 Wiley-Liss, Inc.