Understanding Cocaine Escalation: It’s All About "Incentive Salience"

Why do some people become addicted to cocaine more quickly than others? For decades, scientists have debated whether addiction is driven by sensitization of the psychomotor effect of the drug (getting a bigger effect of the drug over time), sensitization of the motivational effects of the cues (incentive salience) or tolerance to the psychomotor effect of the drug (needing more of the drug to get the same effect). Our latest study using advanced machine vision and genetically diverse subjects has found a different answer: the key driver of escalation is incentive salience.

The Big Question

We wanted to determine which behavioral mechanism truly drives the escalation of cocaine use. Is it because the subject becomes more sensitive to the drug's physical effects, or because they develop a "wanting" for the drug cues that outweighs the actual "liking" of the drug? To find out, we tracked individual behavior across different stages of drug access to see which traits predicted who would eventually use the most cocaine.

The Study: Watching the Brain’s "Wanting" System

We used a sophisticated setup that combined cocaine self administration with machine vision pose estimation. This technology allowed us to track the exact movements of rats in their chambers with scientific precision. We focused on three main stages:

• Short Access (ShA): Two hours of drug availability per day.

• Long Access (LgA): Six hours of drug availability, which typically leads to escalated use.

• Withdrawal/Abstinence: Periods where the drug was not available to see how "craving" intensified.

We specifically measured pre lever activity, which is how much the rats moved and investigated the drug lever beforeit was even available for use. This acts as a pure measure of their motivation or "wanting" for the drug.

What We Discovered

Our findings challenge long held beliefs about how addiction progresses:

• Incentive Salience is the Catalyst: We found that pre lever activity during the early stages of drug use was the best predictor of who would eventually escalate their cocaine intake during long access.

• Sensitization and Tolerance are Not the Drivers: While individuals showed strong differences in their physical response to cocaine (some becoming more sensitive and others more tolerant), these differences had zero effecton how much cocaine they actually chose to take.

• Susceptibility is Not Fixed: We discovered that even rats with low initial motivation eventually "caught up" to the high motivation group. With enough drug exposure, initially resistant individuals became sensitized and escalated their use to the same high levels as the most susceptible subjects.

• Abstinence Fires Up Craving: Short periods of abstinence (like a weekend) significantly boosted pre lever activity, suggesting that being away from the drug actually "incubates" the craving.

  
  

Why It Matters

This research proves that the drive to use cocaine is powered by the brain's motivational system, not its physical reaction to the drug itself. By identifying incentive salience as the primary driver, we have a new way to predict addiction vulnerability before it becomes severe.

The fact that "resistant" individuals can eventually become just as addicted as "susceptible" ones is a vital warning for public health. It suggests that with high enough exposure, almost any brain can be rewired for addiction. We believe that by using video tracking to measure this "wanting" behavior, we can better test new medications that specifically target craving, helping people break the cycle of addiction more effectively.

Reference: Ramborger, J., Mosquera, J., Brennan, M., Sichel, B., Othman, D., Plasil, S., Sneddon, E., Zahedi, S., Morgan, A., Chonwattanagul, S., Bai, K., China, L., La, T., Maturin, L., Carrette, L. L. G., & George, O. (2026). Incentive salience, not psychomotor sensitization or tolerance, drives escalation of cocaine self-administration in heterogeneous stock rats. Neuropsychopharmacology. https://doi.org/10.1038/s41386-026-02350-0