PT  - JOURNAL ARTICLE
AU  - Nicholas M. Timme
AU  - Baofeng Ma
AU  - David Linsenbardt
AU  - Ethan Cornwell
AU  - Taylor Galbari
AU  - Christopher Lapish
TI  - Compulsive drinking is associated with neural activity patterns reflecting diminished behavioral control and enhanced seeking representations in dorsal medial prefrontal cortex
AID  - 10.1101/2021.03.15.435169
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.15.435169
4099  - http://biorxiv.org/content/early/2021/03/16/2021.03.15.435169.short
4100  - http://biorxiv.org/content/early/2021/03/16/2021.03.15.435169.full
AB  - 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 StatementThe authors have declared no competing interest.