Compulsive Disorders Are Not Just Habits: The Role of Neuroinflammation

This study showed that inflammation in a specific brain region associated with action control can lead to excessively goal-oriented behavior, rather than automatic habits. In rats, the induction of striatal inflammation caused the animals to maintain consequence-driven actions even in situations that would normally generate habits. This effect was linked to astrocyte activation, suggesting that these cells play a central role in compulsivity. The results challenge traditional theories and indicate new avenues for understanding and treating compulsive disorders.

Several mental disorders characterized by compulsive behaviors, such as obsessive-compulsive disorder and substance use disorder, share an important brain alteration called striatal neuroinflammation. This inflammation occurs in a deep brain region known as the striatum, which plays a central role in controlling actions and decisions.

People with these disorders often persistently repeat behaviors, even when they know these actions are harmful and even when they would like to stop, raising the question of why the brain starts functioning this way.

For many years, the main explanation for compulsions was the idea that they arise when the brain stops acting based on conscious goals and begins to function predominantly through automatic habits. In other words, it was believed that people with compulsive disorders act less guided by goals and consequences and more by repeated and rigid responses.

However, recent studies have begun to question this traditional view, especially in the case of substance use disorder, suggesting that these individuals may, in fact, be excessively focused on goals, even if those goals are harmful. This contradiction has generated an intense debate in the field of neuroscience.

To clarify this issue, the researchers in this study sought to understand the problem from the perspective of basic neural mechanisms. Instead of simply observing behavior, they investigated how inflammation in specific brain regions can alter the balance between two fundamental systems of action control: the goal-oriented system and the habit-based system.

These two systems function in parallel in the brain and have been extensively studied in animals and humans, showing great similarity between species.

Previous studies have demonstrated that these two types of action control depend on distinct brain circuits within the network connecting the cerebral cortex to the striatum. When one of these circuits is damaged or experimentally switched off, the other tends to dominate behavior.

However, these classic models generally use brain lesions or intense pharmacological blockades, which do not accurately reflect what happens in real psychiatric disorders. In these clinical conditions, there is no massive destruction of neurons, especially in the initial stages, but rather more subtle alterations in brain function.

Recent research indicates that chronic stress is a common factor in many psychiatric disorders and that its effects on the brain are often mediated by inflammatory processes. In fact, neuroimaging studies and post-mortem analyses consistently show signs of inflammation in the striatum of people with obsessive-compulsive disorders.

Based on this, the authors decided to reproduce this type of inflammation in a controlled manner in rats to observe how it would affect the control of actions.

To achieve this, the researchers induced a localized inflammatory response in the posterior dorsomedial striatum, an area known to be essential for goal-oriented actions. They used a substance derived from bacteria, lipopolysaccharide, which is widely used in research to simulate inflammation in the brain.

This substance was injected directly into this specific region of the rats' brains, allowing the observed effects to be accurately attributed to local inflammation.

After inducing inflammation, the rats underwent a series of behavioral tests that assess how animals choose their actions. Some tests measured choices guided by environmental cues, while others evaluated free choices. One of the most important tests was the outcome devaluation procedure, which allows for a clear distinction between goal-oriented actions and habits.

In this test, if the animal reduces an action when the outcome ceases to be valuable, this indicates that it is acting in a goal-oriented manner and taking into account the consequences of its actions.

The researchers specifically chose the posterior dorsomedial striatum because this region is considered, in rodents, the main neural center for goal-oriented actions.

Furthermore, this area is equivalent to the caudate nucleus in humans, a region that shows elevated signs of inflammation in people with obsessive-compulsive disorder. Therefore, the animal model used has strong relevance for understanding human disorders.

The behavioral results were surprising. Instead of inducing more automatic and habitual behavior, striatal inflammation led the rats to exhibit excessive goal-oriented control. Even under conditions that normally favor habit formation, the animals continued to adjust their actions based on the value of the outcomes.

Analyses of brain tissue indicated that this effect was associated with an increase and activation of astrocytes, a type of glial cell that supports neurons and regulates the brain environment.

To directly test the role of astrocytes in this process, the researchers conducted an additional experiment using chemogenetic techniques. They selectively activated specific pathways within striatal astrocytes during behavioral tests.

This manipulation altered the activity of nearby neurons and modified the control of actions again, confirming that astrocytes play a crucial role in regulating goal-oriented behavior.

Overall, these results challenge the widely accepted idea that compulsivity results exclusively from the predominance of habits. Instead, the study suggests that inflammation in the striatum can lead to an excess of goal-oriented control, making behavior rigid and maladaptive.

Thus, individuals with striatal neuroinflammation may not be trapped in automatic habits, but rather excessively focused on specific goals, even when those goals are harmful. These findings indicate that future treatments should seek to restore the proper balance between the different systems controlling action.

READ MORE:

Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting astrocyte function

Arvie Rodriguez Abiero, Joanne M. Gladding, Jacqueline A. Iredale, Hannah R. Drury, Elizabeth E. Manning, Christopher V. Dayas, Amolika Dhungana, Kiruthika Ganesan, Karly Turner, Serena Becchi, Michael D. Kendig, Christopher Nolan, Bernard Balleine, Alessandro Castorina, Louise Cole, Kelly J. Clemens, and Laura A. Bradfield

Neuropsychopharmacology.  51, pages 486–496 (2026)27 September 2025

DOI: 10.1038/s41386-025-02247-4

Abstract|:

Compulsive actions are typically thought to reflect the dominance of habits over goal-directed action. To investigate this, we mimicked the striatal neuroinflammation that is frequently exhibited in individuals with compulsive disorders in rats, by injecting the endotoxin lipopolysaccharide into the posterior dorsomedial striatum, and assessed the consequences for behavioural control. Surprisingly, this manipulation caused rats to acquire and maintain goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical analyses indicated that these behaviours were a result of astrocytic proliferation. To probe this further, we chemogenetically activated the Gi-pathway in striatal astrocytes, which altered the firing properties of nearby medium spiny neurons and modulated goal-directed action control. Together, results show that striatal neuroinflammation is sufficient to bias action selection toward excessive goal-directed control via dysregulated astrocyte function. If translatable, our findings suggest that, contrary to conventional views, individuals with striatal neuroinflammation might be more prone to maladaptive goal-directed actions than habits, and future interventions should aim to restore appropriate action control.