Summary:
Researchers have found that cocaine narrows natural, adaptable behavior into compulsive, repetitive routines by targeting an action‑selection circuit in the ventrolateral striatum (VLS). Using a new deep‑learning tracking system called STEREO, the team demonstrated that rebalancing opposing direct and indirect striatal pathways can immediately interrupt drug‑induced stereotyped actions and restore behavioral flexibility.
Key Facts:
- Hijacking an existing action‑selection circuit: Cocaine does not create a new motor pattern but co‑opts a VLS circuit normally devoted to orofacial actions like grooming and licking.
- Push‑pull control by opposing pathways: Stimulating the indirect pathway halts cocaine‑driven repetitive behavior and restores varied actions, while activating the direct pathway produces rigid, repetitive behavior even in drug‑free animals.
- Deep‑learning behavioral tracking (STEREO): The research team developed STEREO, an automated AI computer‑vision platform that classifies full behavioral repertoires from raw video and revealed that five days of cocaine exposure caused licking to dominate over 60% of active time.
Source: Hebrew University of Jerusalem
Loss of behavioral flexibility is a core feature of substance use disorders and many neuropsychiatric conditions. Over time, exploratory and varied actions narrow into rigid, repetitive routines.
A team led by PhD researchers Ben Jerry Gonzales and Itay Shalom, supervised by 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, identified the neural circuitry that converts flexible action selection into compulsive motor output.
Their work shows that repeated cocaine exposure seizes an existing striatal action‑selection mechanism and biases it toward persistent repetition. By manipulating the balance between direct and indirect pathway activity in the ventrolateral striatum, the researchers could rapidly switch repetitive behaviors off and return animals to fluid, adaptive movement patterns.
Capturing the Full Behavioral Repertoire with STEREO
To measure how a varied set of natural behaviors collapses into stereotypy, the team developed STEREO, a deep‑learning framework that classifies ethologically meaningful actions directly from high‑speed video. Unlike manual scoring or single‑action assays, STEREO tracks the entire repertoire continuously, enabling quantification of complex transitions over extended time periods.
Using repeated cocaine administration as a model of behavioral inflexibility, the researchers documented a dramatic shift: initially diverse behaviors such as rearing, sniffing, and walking progressively narrowed. By the fifth day of exposure, compulsive licking of the floor and enclosure walls consumed more than 60% of the animals’ active time—behavior that was essentially absent in drug‑naive mice.
Opposing Circuits in the Ventrolateral Striatum
The behavioral rigidity mapped to the ventrolateral striatum (VLS), a basal ganglia subregion controlling fine orofacial movements. Within the VLS, the canonical direct and indirect pathways exert opposite control over motor execution:
- Indirect pathway (“The Brake”): Optogenetic activation of indirect pathway neurons immediately interrupted cocaine‑driven licking and allowed animals to resume varied exploratory actions. When stimulation stopped, the repetitive behavior returned. Silencing the indirect pathway prolonged repetitive bouts and impaired switching.
- Direct pathway (“The Accelerator”): Inhibiting the direct pathway reduced cocaine‑induced stereotypy, while activating it in drug‑naive animals produced rigid, repetitive orofacial actions that mimicked drug effects.
“Cocaine does not create an entirely new behavioral program,” said co‑lead author Ben Jerry Gonzales. “It hijacks a circuit the brain already uses for natural actions and biases it toward persistent repetition.”
Implications for Addiction and Movement Disorders
Because the VLS normally coordinates context‑appropriate grooming, licking, and feeding, these results indicate that addictive drugs do not invent maladaptive behaviors; they lock existing action‑selection machinery into sustained activation. This biased recruitment of direct‑pathway circuits transforms flexible selection into compulsive motor output.
Given that distinct striatal territories regulate different motor repertoires—from limb movements to head orientation—similar imbalances between direct and indirect pathways in other striatal regions could underlie stereotypies and compulsive rituals observed in conditions such as Tourette syndrome, obsessive‑compulsive disorder (OCD), and Parkinson’s disease.
STEREO also provides a scalable tool for testing therapeutic interventions designed to restore behavioral flexibility across a range of neurological and psychiatric disorders, offering objective, high‑throughput behavioral readouts.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The original journal paper was reviewed in full.
- Additional context was added by editorial 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 (Open Access): Current Biology (September 22, 2026). Title: “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 enable flexible selection of context‑appropriate actions, and their dysfunction contributes to disorders characterized by behavioral rigidity. To determine whether rigidity arises from biased engagement of the same circuits that normally support flexibility, the authors developed STEREO, a deep‑learning framework that classifies ethologically relevant actions from raw video.
Integrating STEREO with population recordings and pathway‑specific manipulations in freely behaving mice, they identified a VLS circuit that governs flexible and rigid selection of orofacial behaviors. Repeated psychostimulant exposure progressively collapsed a rich behavioral repertoire into dominance by a single orofacial action, accompanied by recruitment of both direct‑ and indirect‑pathway neurons in the VLS.
Causal experiments revealed opponent control within a shared selection mechanism: indirect‑pathway activation rapidly relieved cocaine‑induced rigidity, while direct‑pathway activation alone produced drug‑like stereotyped bouts. These results show that biased recruitment of direct‑pathway circuits converts flexible action selection into compulsive motor output.