Assessing contributions of nucleus accumbens shell subregions to reward-seeking behavior

Background: The nucleus accumbens (NAc) plays a key role in brain reward processes including drug seeking and reinstatement. Several anatomical, behavioral, and neurochemical studies discriminate between the limbic-associated shell and the motor-associated core regions. Less studied is the fact that the shell can be further subdivided into a dorsomedial shell (NAc_DMS) and an intermediate zone (NAc_INT) based on differential expression of transient c-Fos and long-acting immediate-early gene δFosB upon cocaine sensitization. These disparate expression patterns suggest that NAc shell subregions may play distinct roles in reward-seeking behavior. In this study, we examined potential differences in the contributions of the NAc_DMS and the NAc_INT to reinstatement of reward-seeking behavior after extinction. Methods: Rats were trained to intravenously self-administer cocaine, extinguished, and subjected to a reinstatement test session consisting of an intracranial microinfusion of either amphetamine or vehicle targeted to the NAc_DMS or the NAc_INT. Results: Small amphetamine microinfusions targeted to the NAc_DMS resulted in statistically significant reinstatement of lever pressing, whereas no significant difference was observed for microinfusions targeted to the NAc_INT. No significant difference was found for vehicle microinfusions in either case. Conclusion: These results suggest heterogeneity in the behavioral relevance of NAc shell subregions, a possibility that can be tested in specific neuronal populations in the future with recently developed techniques including optogenetics.