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Articles, Systems/Circuits

Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking

Isabel F. Augur, Andrew R. Wyckoff, Gary Aston-Jones, Peter W. Kalivas and Jamie Peters
Journal of Neuroscience 28 September 2016, 36 (39) 10174-10180; DOI: https://doi.org/10.1523/JNEUROSCI.0773-16.2016
Isabel F. Augur
1Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, and
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Andrew R. Wyckoff
1Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, and
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Gary Aston-Jones
1Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, and 2Rutgers University and Rutgers Biomedical and Health Sciences, Piscataway, New Jersey 08854
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Peter W. Kalivas
1Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, and
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Jamie Peters
1Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina 29425, and
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Abstract

The ventromedial prefrontal cortex (vmPFC) has been shown to negatively regulate cocaine-seeking behavior, but the precise conditions by which vmPFC activity can be exploited to reduce cocaine relapse are currently unknown. We used viral-mediated gene transfer of designer receptors (DREADDs) to activate vmPFC neurons and examine the consequences on cocaine seeking in a rat self-administration model of relapse. Activation of vmPFC neurons with the Gq-DREADD reduced reinstatement of cocaine seeking elicited by cocaine-associated cues, but not by cocaine itself. We used a retro-DREADD approach to confine the Gq-DREADD to vmPFC neurons that project to the medial nucleus accumbens shell, confirming that these neurons are responsible for the decreased cue-induced reinstatement of cocaine seeking. The effects of vmPFC activation on cue-induced reinstatement depended on prior extinction training, consistent with the reported role of this structure in extinction memory. These data help define the conditions under which chemogenetic activation of extinction neural circuits can be exploited to reduce relapse triggered by reminder cues.

SIGNIFICANCE STATEMENT The ventromedial prefrontal cortex (vmPFC) projection to the nucleus accumbens shell is important for extinction of cocaine seeking, but its anatomical proximity to the relapse-promoting projection from the dorsomedial prefrontal cortex to the nucleus accumbens core makes it difficult to selectively enhance neuronal activity in one pathway or the other using traditional pharmacotherapy (e.g., systemically administered drugs). Viral-mediated gene delivery of an activating Gq-DREADD to vmPFC and/or vmPFC projections to the nucleus accumbens shell allows the chemogenetic exploitation of this extinction neural circuit to reduce cocaine seeking and was particularly effective against relapse triggered by cocaine reminder cues.

  • DREADD
  • extinction
  • infralimbic
  • memory
  • nucleus accumbens shell
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The Journal of Neuroscience: 36 (39)
Journal of Neuroscience
Vol. 36, Issue 39
28 Sep 2016
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Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking
Isabel F. Augur, Andrew R. Wyckoff, Gary Aston-Jones, Peter W. Kalivas, Jamie Peters
Journal of Neuroscience 28 September 2016, 36 (39) 10174-10180; DOI: 10.1523/JNEUROSCI.0773-16.2016

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Chemogenetic Activation of an Extinction Neural Circuit Reduces Cue-Induced Reinstatement of Cocaine Seeking
Isabel F. Augur, Andrew R. Wyckoff, Gary Aston-Jones, Peter W. Kalivas, Jamie Peters
Journal of Neuroscience 28 September 2016, 36 (39) 10174-10180; DOI: 10.1523/JNEUROSCI.0773-16.2016
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Keywords

  • DREADD
  • extinction
  • infralimbic
  • memory
  • nucleus accumbens shell

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JNeurosci   Print ISSN: 0270-6474   Online ISSN: 1529-2401