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Involvement of cAMP-Dependent Protein Kinase in the Nucleus Accumbens in Cocaine Self-Administration and Relapse of Cocaine-Seeking Behavior

By David W. Self, Lisa M. Genova, Bruce T. Hope, William J. Barnhart, Jennifer J. Spencer and Eric J. Nestler

Abstract

cAMP-dependent protein kinase (PKA) in the nucleus accumbens (NAc) has been implicated in cocaine addiction because (1) cocaine reinforcement is mediated by dopamine receptors that modulate cAMP formation, and (2) repeated exposure to cocaine upregulates the cAMP system in NAc neurons. This study tested PKA involvement in cocaine self-administration and relapse of cocaine-seeking behavior by infusing cAMP analogs that activate or inhibit PKA into the NAc of rats. Bilateral intra-NAc infusions of the PKA inhibitor R p-cAMPS reduced baseline cocaine self-administration, shifted the dose– response curve for cocaine self-administration to the left, and induced relapse of cocaine-seeking behavior after extinction from cocaine self-administration, consistent with an enhancement of cocaine effects in each paradigm. In contrast, pretreatment with intra-NAc infusions of a PKA activator, S p-cAMPS o

Year: 1998
OAI identifier: oai:CiteSeerX.psu:10.1.1.318.5596
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