SEOUL, March 09 (AJP) - A joint research team from South Korea and the United States has identified a specific neural circuit in the brain that controls drug-seeking behavior. This discovery challenges the long-held belief that addiction relapse is caused by a general decline in willpower or a permanent loss of function in the prefrontal cortex. A team led by Professor Baek Se-bum of the Korea Advanced Institute of Science and Technology (KAIST) and Professor Lim Byung-kook of the University of California, San Diego (UCSD) announced on March 9 that they have discovered how specific inhibitory neurons in the prefrontal cortex regulate cocaine addiction.
Addiction is notoriously difficult to treat because even minor triggers can revive intense cravings long after a person has stopped using drugs. Until now, this phenomenon was largely attributed to the weakening of the prefrontal cortex (PFC), the area of the brain responsible for impulse control. However, the new findings indicate that relapse is actually driven by an imbalance in specific neural circuits rather than a simple decrease in overall brain activity.
The study focused on parvalbumin-positive (PV) inhibitory neurons. These cells act as a brake gate in the brain by suppressing the activity of other neurons to maintain neural balance. By monitoring mice exposed to cocaine, the researchers tracked when these neurons activated and how they sent signals to lower brain regions.
The researchers found that PV neurons, which make up 60 to 70 percent of inhibitory cells in the PFC, became highly active when the mice sought cocaine. When the mice underwent extinction training—a process to stop them from seeking the drug—the activity of these cells significantly decreased. This suggests that the behavior of PV cells is not permanently damaged by addiction but can be readjusted through behavioral training.
To confirm the role of these cells, the team artificially suppressed PV neuron activity, which resulted in a major reduction in cocaine-seeking behavior. Conversely, activating these cells caused the mice to continue seeking drugs even after their training was complete. This effect was specific to drug addiction and did not occur with natural rewards like sugar water, nor was it observed in other types of inhibitory cells such as somatostatin (SOM) neurons.
The study identified that the PFC sends these regulatory signals to the ventral tegmental area (VTA), a core part of the brain reward system. The PV neurons act as a control switch in this pathway, influencing dopamine signals to determine whether to maintain or suppress addictive behavior. The findings prove that relapse is determined by whether this specific pathway between the PFC and the reward circuit is properly regulated.
Professor Baek Se-bum stated that the research shows drug addiction is a circuit-level problem caused by a collapse in the regulatory balance of specific neurons and downstream circuits. He noted that the discovery of PV cells acting as a gate for addictive behavior provides a critical lead for developing precision-targeted treatment strategies in the future.
The study, with Dr. Chung Min-ju of UCSD as the lead author, was published online in the journal Neuron on February 26. The work was supported by institutional funding and international research grants.
(Paper information)
Journal: Neuron
Title: Distinct Interneuronal Dynamics Selectively Gate Target-Specific Cortical Projections in Drug Seeking
DOI: https://doi.org/10.1016/j.neuron.2026.01.002
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