Summary:
Researchers have discovered that cocaine restricts natural, flexible behaviors into compulsive, repetitive patterns by hijacking a specific action-selection circuit in the ventrolateral striatum (VLS). Using a new deep-learning tracking tool called STEREO, the team showed that rebalancing opposing direct and indirect neural pathways can instantly halt drug-induced repetitive actions and restore behavioral flexibility.
Key Facts:
- Hijacking Normal Action Selection: Cocaine does not create a novel motor program; instead, it co-opts an existing circuit in the ventrolateral striatum (VLS) normally dedicated to natural orofacial actions such as grooming and licking.
- Opposing Pathway Push-Pull: Stimulating the striatal indirect pathway instantly halts cocaine-induced repetitive behaviors and restores varied actions, whereas activating the direct pathway triggers rigid, repetitive behaviors even in drug-free animals.
- Deep-Learning Behavioral Tracking (STEREO): The researchers developed “STEREO,” an automated AI computer vision platform that tracks entire behavioral repertoires from raw video, capturing how five days of cocaine exposure caused licking behavior to dominate more than 60% of an animal’s active time.
Source: Hebrew University of Jerusalem
One of the defining hallmarks of substance use disorders and various neuropsychiatric conditions is the loss of behavioral flexibility. Over time, dynamic exploration and varied actions narrow into rigid, repetitive, and compulsive routines.
Now, a study led by PhD researchers Ben Jerry Gonzales and Itay Shalom under the supervision of Prof. Ami Citri at the Edmond and Lily Safra Center for Brain Sciences (ELSC) and the Institute of Life Sciences at the Hebrew University of Jerusalem has pinpointed the precise neural circuitry responsible for this shift.
The research reveals that cocaine narrows an animal’s behavioral repertoire by seizing control of an existing action-selection pathway in the striatum. By manipulating the push-pull dynamics of opposing neural circuits, the team was able to rapidly switch repetitive behaviors off and restore fluid, adaptive movements.
Capturing the Whole Repertoire with STEREO
To quantify how a diverse range of natural behaviors narrows over time, the team developed STEREO, a machine learning system capable of classifying and tracking natural behaviors directly from high-speed video.
Traditionally, behavioral neuroscience relies on manual human scoring or focuses on single isolated actions, making it difficult to analyze complex behavioral transitions across long periods.
“We wanted to capture behavior as an observer actually sees it: grooming, licking, exploring, but this was impossible to score manually,” said co-lead author Itay Shalom. “STEREO allowed us to track the entire behavioral repertoire progressively narrowed until one type of action came to dominate.”
Using repeated cocaine administration as an experimental model of behavioral inflexibility, the researchers recorded a dramatic transformation. Initially varied movements, such as environmental rearing, sniffing, and walking, progressively collapsed into focused stereotypy. By the fifth day of exposure, compulsive licking of the floor and enclosure walls dominated more than 60% of the animals’ active time, a behavior virtually absent in drug-naive mice.
Opposing Circuits in the Ventrolateral Striatum
The researchers mapped this behavioral rigidity to the ventrolateral striatum (VLS), a subregion of the basal ganglia specifically engaged in controlling fine movements of the mouth, tongue, and face. Within the VLS, two classically defined neural circuits, the direct and indirect pathways, compete to control motor execution:
- The Indirect Pathway (“The Brake”): Optogenetic activation of indirect pathway neurons immediately interrupted cocaine-driven stereotyped licking, instantly allowing the animals to switch back to varied exploratory actions. When stimulation ceased, the repetitive behavior resumed. Conversely, silencing this pathway lengthened bouts of repetitive licking, impairing the ability to switch tasks.
- The Direct Pathway (“The Accelerator”): Inhibiting the direct pathway significantly attenuated cocaine-induced stereotypy. Strikingly, activating this pathway in drug-naive animals was sufficient to induce rigid, repetitive behaviors identical to those caused by cocaine exposure.
“Cocaine does not appear to create an entirely new behavioral program,” explained co-lead author Ben Jerry Gonzales. “It takes control of a circuit the brain already uses for natural actions and pushes behavior toward persistent repetition.”
Broader Implications for Addiction and Movement Disorders
Because the ventrolateral striatum is normally responsible for context-appropriate grooming, licking, and feeding, the findings demonstrate that addictive substances do not invent maladaptive actions out of whole cloth. Instead, drugs of abuse hijack the brain’s existing action-selection apparatus, locking it into persistent activation.
The team notes that because distinct topological regions of the striatum regulate different motor repertoires (from limb movement to head turning), similar imbalances between direct and indirect pathways in other striatal domains could explain stereotypies and compulsive rituals seen in Tourette syndrome, obsessive-compulsive disorder (OCD), and Parkinson’s disease.
Furthermore, the introduction of STEREO offers a scalable methodology for neuroscientists to evaluate therapeutic compounds aimed at restoring behavioral flexibility across a wide spectrum of neurological disorders.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this Addiction and Neuroscience Research:
- Media Contact: Yarden Mills
- Source: Hebrew University of Jerusalem
- Image Credit: Image credited to Neuroscience News
- Original Research is Open Access: Current Biology (September 22, 2026). “Opponent ventrolateral striatal circuits regulate behavioral flexibility and rigidity.” Authors: Ben J. Gonzales, Itay Shalom, David M. Lipton, Hagit Turm, Jed Noble, Massimiliano Festuccia, Maya Groysman, and Ami Citri.
- DOI: 10.1016/j.cub.2026.08.068
Abstract
Opponent ventrolateral striatal circuits regulate behavioral flexibility and rigidity
Basal ganglia circuits support the flexible selection of context-appropriate actions, and their dysfunction underlies pathologies defined by behavioral rigidity. Whether such rigidity reflects biased engagement of the same circuits that normally enable flexibility is unknown.
To study behavior across adaptive and maladaptive contexts, we developed a deep-learning framework that classifies ethologically meaningful actions from raw video (STEREO). To associate striatal circuit function with flexible and rigid behavioral states, we integrated STEREO with population recordings and pathway-specific manipulations in freely behaving mice, identifying a striatal circuit that governs flexible and rigid selection of orofacial behaviors.
Using a psychostimulant to induce pathological rigidity, we found that repeated exposure progressively collapses a rich behavioral repertoire into persistent dominance of a single orofacial action, with concurrent recruitment of ventrolateral striatal direct- and indirect-pathway neurons.
Causal interrogation revealed opponent control within a shared selection mechanism: indirect-pathway activation rapidly alleviated cocaine-induced rigidity, while direct-pathway activation alone was sufficient to drive drug-mimetic stereotyped bouts.
These findings demonstrate that biased recruitment of striatal direct-pathway circuits transforms flexible action selection into compulsive motor output.
