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Compulsive drinking is associated with neural activity patterns reflecting diminished behavioral control and enhanced seeking representations in dorsal medial prefrontal cortex

View ORCID ProfileNicholas M. Timme, Baofeng Ma, David Linsenbardt, Ethan Cornwell, Taylor Galbari, Christopher Lapish
doi: https://doi.org/10.1101/2021.03.15.435169
Nicholas M. Timme
1Psychology Department, Indiana University – Purdue University Indianapolis, Indianapolis, IN, 46237
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  • For correspondence: nicholas.m.timme@gmail.com
Baofeng Ma
1Psychology Department, Indiana University – Purdue University Indianapolis, Indianapolis, IN, 46237
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David Linsenbardt
2Department of Neurosciences, University of New Mexico, Albuquerque, NM, 87131
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Ethan Cornwell
1Psychology Department, Indiana University – Purdue University Indianapolis, Indianapolis, IN, 46237
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Taylor Galbari
1Psychology Department, Indiana University – Purdue University Indianapolis, Indianapolis, IN, 46237
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Christopher Lapish
1Psychology Department, Indiana University – Purdue University Indianapolis, Indianapolis, IN, 46237
3Stark Neurosciences Research Institute, Indiana University – Purdue University Indianapolis, Indianapolis, IN, 46237
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Abstract

Drinking despite negative consequences (compulsive drinking) is a central contributor to high-risk alcohol intake and is associated with poor treatment outcomes in humans. We used a rodent model of compulsive drinking to examine the role played by dorsal medial prefrontal cortex (dmPFC), a brain region involved in maladaptive decision-making in addiction, in this clinically critical phenomenon. We developed novel advances in principal component and change point analyses to dissect neural population representations of specific decision-making variables. Compulsive subjects showed weakened representations of behavioral control signals that relate to drinking within a trial, but strengthened session-wide seeking state representations that were associated with drinking engagement at the start of each drinking opportunity. Finally, chemogenetic-based excitation of dmPFC prevented escalation of compulsive drinking. Collectively, these data indicate that compulsive drinking is associated with alterations in dmPFC neural activity that underlie diminished behavioral control and enhanced seeking.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted March 16, 2021.
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Compulsive drinking is associated with neural activity patterns reflecting diminished behavioral control and enhanced seeking representations in dorsal medial prefrontal cortex
Nicholas M. Timme, Baofeng Ma, David Linsenbardt, Ethan Cornwell, Taylor Galbari, Christopher Lapish
bioRxiv 2021.03.15.435169; doi: https://doi.org/10.1101/2021.03.15.435169
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Compulsive drinking is associated with neural activity patterns reflecting diminished behavioral control and enhanced seeking representations in dorsal medial prefrontal cortex
Nicholas M. Timme, Baofeng Ma, David Linsenbardt, Ethan Cornwell, Taylor Galbari, Christopher Lapish
bioRxiv 2021.03.15.435169; doi: https://doi.org/10.1101/2021.03.15.435169

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