Abstract
Drugs of abuse affect behavior by altering neuronal communication within the brain. Previous research examining the effects of intraperitoneally administered cocaine has revealed that cocaine alters excitatory glutamatergic signaling, both directly through regulation of synaptic function, and indirectly through regulation of cellular excitability in areas of the drug reward circuitry such as the nucleus accumbens (NAcc) and ventral tegmental area. We have now extended these findings by testing the hypothesis that self-administration of cocaine might elicit similar alterations in excitatory signaling in the NAcc shell. We observed that cocaine self-administration reduces synaptically evoked excitatory responses recorded extracellularly in the NAcc shell compared to saline self-administration. This alteration was not accompanied by alterations in paired pulse ratio of synaptically evoked responses or in potentiation of these responses by application of the adenylyl cyclase activator forskolin. This reduction in glutamatergic signaling may be one mechanism by which cocaine exerts its long-term behavioral effects.
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Acknowledgements
We thank Carlo Malabanan, Jamie Yates, and Tasneem Ansari of the Mouse Metabolic Phenotyping Center for assistance with jugular catheterization surgeries, and David Self and the members of his lab for helpful advice. This work was supported by a NARSAD young investigator award, as well as NIDA support (DA14151 to NLSS; DA 19112 to DGW) and NIMH support (MH65215, CMO).
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Schramm-Sapyta, N., Olsen, C. & Winder, D. Cocaine Self-Administration Reduces Excitatory Responses in the Mouse Nucleus Accumbens Shell. Neuropsychopharmacol 31, 1444–1451 (2006). https://doi.org/10.1038/sj.npp.1300918
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DOI: https://doi.org/10.1038/sj.npp.1300918
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