Compulsive alcohol drinking in rodents is associated with altered representations of behavioral control and seeking in dorsal medial prefrontal cortex

A key feature of compulsive alcohol drinking is continuing to drink despite negative consequences. To examine the changes in neural activity that underlie this behavior, compulsive alcohol drinking was assessed in a validated rodent model of heritable risk for excessive drinking (alcohol preferring (P) rats). Neural activity was measured in dorsal medial prefrontal cortex (dmPFC-a brain region involved in maladaptive decision-making) and assessed via change point analyses and novel principal component analyses. Neural population representations of specific decision-making variables were measured to determine how they were altered in animals that drink alcohol compulsively. Compulsive animals showed weakened representations of behavioral control signals, but strengthened representations of alcohol seeking-related signals. Finally, chemogenetic-based excitation of dmPFC prevented escalation of compulsive alcohol drinking. Collectively, these data indicate that compulsive alcohol drinking in rats is associated with alterations in dmPFC neural activity that underlie diminished behavioral control and enhanced seeking. Compulsive alcohol drinking is a core feature of alcohol use disorder. Here the authors find that in rodents, neural signals in a key decision-making brain region (dmPFC) shift from behavioral control to alcohol seeking during compulsive alcohol drinking behaviour.

Automated summary

This study investigates the neural activity changes underlying compulsive alcohol drinking behavior using a validated rodent model. The findings suggest that in rats with compulsive alcohol drinking, neural signals in a key decision-making brain region shift from behavioral control signals to alcohol seeking signals.