Researchers from the Hebrew University have identified a deep neural network in the brain that works specifically against the feeling of reward – and may serve as an innovative therapeutic target for dealing with drug addiction.
Why do so many cocaine addicts relapse? A new study conducted at the Hebrew University of Jerusalem reveals that a unique neural network in the brain, which operates in an “anti-reward” state, becomes particularly active during withdrawal symptoms – increasing feelings of distress and pushing users back to use the drug. This network may not only be a factor that makes the withdrawal process difficult – but also an internal defense mechanism that helps prevent excessive use, offering new hope for treating addiction.
The study, led by Prof. Jonathan Kopchik and doctoral student Liran Levy from the Faculty of Medicine at the Hebrew University, identified a deep glutamatergic brain network (a group of neurons that function primarily through glutamate, a chemical that transmits information between nerve cells) located in the ventral pallidum, a part of the brain involved in emotions, motivation, reward, and addiction.
This network undergoes long-term changes following cocaine use, withdrawal, and re-exposure. The findings place this network as a central factor in the addiction process—and the brain as an arena for a struggle not only between reward and restraint, but also between pain and comfort.
An emotional journey inside the brain
While the ventral pallidum is known as a region that regulates feelings of pleasure and reward, the group of neurons that was uncovered is less well-known and suppresses dopamine secretion and increases negative emotions. During withdrawal, the activity of this network increases – which intensifies the feeling of discomfort and emotional difficulties. But when cocaine returns, the network activity quickly subsides – and the result: a cycle of addiction based on the search for emotional relief.
“This network functions like a switch,” explains Prof. Jonathan Kupchik. “When it’s very active, it can push the person to use again – just to escape the mental pain.”
The study also shows that the “anti-reward” network forms tighter connections with other brain regions responsible for emotional processing and reward. During withdrawal, these connections are strengthened – which increases sensitivity to negative emotions. When the drug is resumed, the system “resets itself” – and distress is temporarily relieved.
Is pain a defense mechanism?
In another surprising finding, the researchers found that when the anti-reward network was proactively inhibited, the preference for cocaine and the motivation to obtain it actually increased. This finding suggests that the negative signals from the brain may play a protective role – a kind of internal brake that prevents excessive use by making the emotional experience unpleasant.
A new direction in addiction treatment
While most existing treatments focus on reducing the brain's reward system, the findings of this study suggest a different direction: targeting the emotional pain that accompanies the withdrawal process. A deeper understanding of the brain mechanisms that trigger emotional distress – and even the ability to regulate them – may form the basis for a new generation of treatments that address the root of the problem, not just the symptoms.
The study, published by doctoral student Liran A. Levy and Prof. Kopchik of the Center for Addiction Research (ICARe) at the Israel-Canada Medical Research Institute of the Hebrew University of Jerusalem, offers a new framework for understanding addiction – not just as a pursuit of pleasure, but as an escape from pain.
The article was published in the journal Science Advances.
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