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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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    Figure 1.

    Activation of vmPFC with a Gq-DREADD reduces cue-induced cocaine seeking after extinction. A, Active (shaded bars) and inactive (white bars) lever presses are shown for the cue-induced and cocaine-primed reinstatement tests. *p < 0.05, comparing vehicle with CNO for active lever. B, Histological verification of the extent of DREADD expression indicated robust and restricted expression in vmPFC. C, A representative photomicrograph demonstrating expression of the Gq-DREADD (HA tag) located primarily within infralimbic cortex.

  • Figure 2.
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    Figure 2.

    Activation of vmPFC with a Gq-DREADD does not alter cocaine seeking in the presence of cocaine cues after abstinence. A, Neither active (shaded bars) nor inactive (white bars) lever presses differed for CNO versus vehicle-treated animals during the cocaine-seeking test (p > 0.8). B, Histological verification of the extent of DREADD expression indicated robust and restricted expression in vmPFC.

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    Figure 3.

    Activation of the vmPFC projection to the NAshell using a retro-DREADD approach reduces cue-induced reinstatement of cocaine seeking. A, The retro-DREADD approach used to target the vmPFC projection to the NAshell is depicted. CAV2-Cre was infused into the NAshell (blue pipet), and the AAV-DIO-hM3Dq(Gq) DREADD (yellow pipet) was infused into vmPFC. Cre-lox recombination thus restricts expression of the hM3Dq to vmPFC neurons projecting to the NAshell (green). Representative photomicrographs demonstrating expression of the Gq-DREADD (mCherry tag) in vmPFC cell bodies and dendrites (left) and NAshell fibers and terminals (right), relative to the anterior commissure (a.c.). B, Histological verification of the extent of DREADD expression indicated robust and restricted expression in vmPFC. C, Active (shaded bars) and inactive (white bars) lever presses are shown for the cue-induced and cocaine-primed reinstatement tests. *p < 0.05, comparing vehicle with CNO for active lever. D, The number of Fos+ nuclei in vmPFC (per mm2 tissue) induced by a final CNO injection is shown, along with a representative image. *p < 0.05, comparing vehicle with CNO.

  • Figure 4.
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    Figure 4.

    Activation of the vmPFC projection to the NAshell using a retro-DREADD approach does not alter cocaine seeking in the presence of cocaine cues after abstinence. A, Neither active (shaded bars) nor inactive (white bars) lever presses differed for CNO versus vehicle-treated animals during the cocaine-seeking test (p > 0.3). B, Histological verification of the extent of DREADD expression indicated robust and restricted expression in vmPFC.

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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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