Elsevier

Neuroscience Letters

Volume 420, Issue 2, 13 June 2007, Pages 169-173
Neuroscience Letters

When administered into the nucleus accumbens core or shell, the NMDA receptor antagonist AP-5 reinstates cocaine-seeking behavior in the rat

https://doi.org/10.1016/j.neulet.2007.04.063Get rights and content

Abstract

Nucleus accumbens glutamate transmission plays a critical role in cocaine priming-induced reinstatement of drug seeking. Previous studies have demonstrated that systemic or intra-accumbens shell administration of an NMDA receptor antagonist reinstates cocaine-seeking behavior. However, it is unclear if antagonizing NMDA receptors in the nucleus accumbens core or shell subregions will differentially affect cocaine reinstatement. To investigate this possibility, we microinjected the competitive NMDA receptor antagonist AP-5 (0, 3 or 30 μg) into either the nucleus accumbens core or shell and assessed the reinstatement of cocaine-seeking behavior. When microinjected into the shell, both doses of AP-5 produced reinstatement of cocaine seeking. In contrast, when administered into the core, only the highest dose of AP-5 reinstated cocaine-seeking behavior; moreover, the magnitude of this effect was substantially less than when AP-5 was administered into the shell. This study provides evidence that pharmacological antagonism of NMDA receptors in the nucleus accumbens core or shell promotes the reinstatement of cocaine seeking.

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Acknowledgements

This research was supported by grants from the National Institutes of Health (NIH) to R.C.P. (R01 DA15214 and K02 DA18678). K.R.F. was also supported by a National Research Service Award (NRSA) from the NIH (F30 DA19304), as well as an NIH training grant (T32 GM008541-7). H.D.S. was also supported by an NRSA from the NIH (DA16824). The authors would like to thank Audrey Pierce for administrative assistance and Judy Yee for technical support.

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    Present address: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States.

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