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 (NAcDMS) and an intermediate zone (NAcINT) 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 NAcDMS and the NAcINT 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 either an intracranial microinfusion of amphetamine or vehicle targeted to the NAcDMS or the NAcINT. Results Small amphetamine microinfusions targeted to the NAcDMS resulted in statistically significant reinstatement of lever pressing, whereas no statistical difference was observed for microinfusions targeted to the NAcINT. 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.

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Modulators of unconditioned fear are potential targets for developing treatments for anxiety disorders. We used blood oxygen level dependent (BOLD) MRI to investigate the pattern of brain activity during the presentation of a predator odor (cat fur) and a repulsive novel odor, butyric acid (BA), to awake rats. We further tested whether odor-evoked BOLD activation involved oxytocin (OT) and vasopressin V1a receptors. Animals were subdivided into groups either administered an intracerebroventricular injection of artificial cerebrospinal fluid (CSF), an OT receptor antagonist or a V1a antagonist (125 ng/10 μL each) 90 min before studies. BA odor evoked robust brain activation across olfactory, sensory, memory and limbic regions. The magnitude of BOLD activation across these regions was greater for BA than with cat fur. However, blockade of OT and V1a receptors differentially modulated odor evoked neural activity, particularly in the amygdala. OT and V1a antagonism preferentially modulated BOLD responding to BA in the cortical amygdala. While, OT and V1a antagonisms preferentially modulated BOLD responding to cat fur in the central amygdala. The data suggest that although OT receptors modulate BOLD activation in response to a novel and repulsive odor such as BA, vasopressin V1a receptors exert a modulatory influence on the neural response to a predator odor.