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Neuropsychopharmacology. 2006 Jul;31(7):1444-51. Epub 2005 Oct 5.

Cocaine self-administration reduces excitatory responses in the mouse nucleus accumbens shell.

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  • 1Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA.


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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