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Control of within-binge cocaine-seeking by dopamine and glutamate in the core of nucleus accumbens

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Abstract

Rationale

Dopamine and glutamate are thought to interact in the ventral striatum and to play important roles there in the cocaine-seeking of cocaine-experienced animals.

Objectives

We sought to determine the relative roles of the two transmitters in the two major zones of the nucleus accumbens (NAS), the core and shell subregions.

Methods

We assessed the effects of dopamine and glutamate receptor blockade in the core and shell on intravenous cocaine self-administration in rats. Trained animals were allowed to self-administer cocaine for an initial hour, and then D1-type or D2-type dopamine receptor blockers or NMDA-type or AMPA-type glutamate receptor blockers were infused by reverse microdialysis into one of the two regions for an additional 3 h of testing.

Results

The D1-type antagonist SCH23390 and the D2-type antagonist raclopride each increased cocaine intake whereas the AMPA-type antagonist CNQX decreased responding when infused into the core. SCH23390 increased cocaine intake less strongly when infused into the shell, while raclopride and CNQX were each ineffective when infused into the shell. The NMDA-antagonist CPP failed to affect cocaine self-administration when infused into either site.

Conclusions

These findings implicate the core of NAS in the maintenance of established cocaine self-administration in trained animals, despite the fact that the reinforcement of responding in untrained animals appears to results from cocaine actions in the olfactory tubercle and medial shell and not the core of accumbens.

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Acknowledgments

Supported by funding from the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services. We thank Dr. Zhi-Bing You for technical assistance with the reverse-dialysis technique, Drs. Marisela Morales and Hui-Ling Wang for technical assistance with histology, and Eric Thorndike for technical assistance with analyses of self-administration data.

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Author notes

  1. Laurel E. Ecke

    Present address: Department of Neuroscience, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

Authors and Affiliations

  1. Behavioral Neuroscience Branch, Intramural Research Program, NIDA/NIH/DHHS, Baltimore, MD, 21224, USA

    Nobuyoshi Suto, Laurel E. Ecke & Roy A. Wise

  2. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Ave., Baltimore, MD, 21131, USA

    Nobuyoshi Suto

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  1. Nobuyoshi Suto
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Correspondence to Nobuyoshi Suto.

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Suto, N., Ecke, L.E. & Wise, R.A. Control of within-binge cocaine-seeking by dopamine and glutamate in the core of nucleus accumbens. Psychopharmacology 205, 431–439 (2009). https://doi.org/10.1007/s00213-009-1553-0

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  • DOI: https://doi.org/10.1007/s00213-009-1553-0

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