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Differential control over cocaine-seeking behavior by nucleus accumbens core and shell

Abstract

Nucleus accumbens (NAc) dopamine is widely implicated in mediating the reinforcing effects of drugs of abuse. However, the precise function of the NAc itself in drug self-administration has been difficult to establish. Here we show a neural double-dissociation of the behavioral processes that underlie cocaine self-administration in rats. Whereas selective excitotoxic lesions of the NAc core had only a minor effect on the acquisition of responding for cocaine under a standard schedule of continuous reinforcement, these lesions profoundly impaired the acquisition of drug-seeking behavior that was maintained by drug-associated conditioned reinforcers and assessed using a second-order schedule of cocaine reinforcement. In contrast, selective excitotoxic lesions of the NAc shell did not impair drug self-administration or the acquisition of cocaine-seeking, but they did attenuate the psychostimulant effects of cocaine. These results further our understanding of how the NAc controls drug-seeking and drug-taking behavior.

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Figure 1: Excitotoxic lesions of the NAc core and shell.
Figure 2: Representative photomicrographs showing Cresyl Violet-stained and NeuN-stained coronal sections through the NAc in rats with NAc shell or core lesions and sham-operated control subjects.
Figure 3: Acquisition of intravenous cocaine self-administration under a continuous reinforcement schedule.
Figure 4: Cocaine dose-response function.
Figure 5: Acquisition of cocaine self-administration under the second-order schedule.
Figure 6: Effects of NAc lesions on qualitative measures of cocaine self-administration under the second-order schedule.
Figure 7: Effects of NAc lesions on quantitative measures of cocaine self-administration under the second-order schedule.
Figure 8: Effects of NAc lesions on cocaine-induced locomotor activity during self-administration sessions.

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Acknowledgements

This work was supported by an MRC Programme Grant (G9537855) and conducted within the MRC Centre for Behavioural and Clinical Neuroscience. R.I. was supported by an MRC research studentship. We thank D. Eagle, R. Cardinal and M. Aitken for helpful discussions on statistics.

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Correspondence to Barry J Everitt.

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Ito, R., Robbins, T. & Everitt, B. Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat Neurosci 7, 389–397 (2004). https://doi.org/10.1038/nn1217

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