Chronic cocaine use increases impulsivity

By Dr. Liji Thomas, MDReviewed by Lily Ramsey, LLMMar 5 2025

A study in eNeuro finds that impulsivity does not predict cocaine addiction, but prolonged drug use alters brain circuits and heightens impulsive behavior.

Study: Cocaine self-administration increases impulsive decision-making in low-impulsive rats associated with impaired functional connectivity in the mesocorticolimbic system. Image Credit: Orawan Pattarawimonchai/Shutterstock.com

Addiction is often postulated to be the result of impulsive temperament, leading to impulsive choices, though there is no solid evidence to back this assumption. A recent study was published in eNeuro to examine the influence of impulsivity on cocaine addiction.

Introduction

“Substance use disorder (SUD) is characterized by the uncontrollable use of a substance despite harmful consequences.” With its intensely hurtful and malignant personal, social, and economic impact, it has spurred much investigation into its risk factors.

Impulsivity has long been considered a major risk factor for SUD. This temperament trait is defined as the “inability to stop a premature response and impulsive choice.” The impulsive choice is often measured by the frequency of choosing a sure but smaller reward over the risk of failure or harm but with a larger reward for success (risk-choice tasks).

Another marker of impulsive choice is the inability to tolerate delay before obtaining a larger reward, preferring immediate though lesser gratification (delay-discounting tasks, DDT).

People with SUD are commonly impulsive and make risky, impulsive choices, suggesting that increased impulsivity is a marker of SUD. However, findings have been mixed. For instance, heroin and opiate users have relatively unimpaired decision-making abilities compared to cocaine and amphetamine users.

The same mixed findings have been reported in preclinical studies on rats exposed to cocaine. Most research has been based on the 5-choice serial reaction time (5CSRT) task or risk-choice tasks.

About the study

In contrast to much earlier research, the current study used a food reward DDT to classify rats as low-, middle-, and high-impulsivity animals. High-impulsive rats chose, 70% or more of the time, to press a lever that delivered food pellets without delay. In contrast, low-impulsive rats chose a brief delay followed by more pellets for 70% or more of the time.

After training the rats to self-administer cocaine through an implanted catheter, they were then exposed to a punishment phase to identify differences in addiction-like behavior between low- and high-impulsive rats – self-administering cocaine even when randomly punished by electrical foot shocks half of the time.

The cocaine-user rats were re-evaluated for impulsivity by DDT.

Study findings

In the initial training phase, some rats chose larger rewards less often than others, even when there was no delay in the reward.

At delays of up to 16 seconds, all rats chose the bigger reward. When the delay went up to 40 or 60 seconds, the rat behavior diverged. The rats that earlier chose the smaller reward more often at zero delays revealed high-impulsive behavior, selecting the immediate but smaller reward more often, unlike the low-impulsive rats.

After cocaine use was introduced, group differences in learning to self-administer cocaine or in addiction behavior were not noticed. While cocaine self-administration behavior dropped when they received foot shocks, depending on the shock intensity, there was no difference in the decreases between the groups.

Rats who were already self-administering cocaine became more active after taking cocaine. However, the same kind and degree of changes were observed in cocaine-naïve rats. Chronic cocaine use led to similarly higher locomotor responses in both groups after cocaine exposure, indicating a higher sensitivity to cocaine following chronic use.

The surprising finding was that low-impulsive rats showed increasingly impulsive behavior after chronic cocaine use. This change was not observed in the other two groups.

Changes in brain activity

When examined by functional magnetic resonance imaging (fMRI), impulsivity was positively associated with increased cerebral blood volume within the midbrain, thalamus, and auditory cortex of the brain – but only in low-impulsive rats.

With high-impulsive behavior, fewer functional connections were operating between the midbrain and the regulatory frontal cortex – including the orbitofrontal cortex (OFC), primary sensory cortex (S1), and parietal region (PTL) – again, only in low-impulsive rats. Similarly, a loss of functional connections was observed between the thalamus and the frontal cortex in low-impulsive rats. These are reward circuits.

Following cocaine use, all these associations were weakened.

Dopamine (DA) receptors were previously shown by the same authors to be reduced in high-impulsive rats. Restored D3 receptor function decreased such behavior, indicating their key role in impulsive choices in DDT.

In the current study, RNAscope in situ hybridization assays showed lower expression of DA receptors D1, D2, and D3 in the corticostriatal pathways of low-impulsive rats after cocaine use. Conversely, D3 receptors increased slightly in high-impulsive rats.

Implications

Substance use disorders (SUD) have traditionally been considered to be more likely among more impulsive people, but this was not observed in the current study.

Impulsivity did not predict the acquisition of the cocaine habit or increase the odds of cocaine addiction. Rather, chronic cocaine use increased impulsive behavior in naturally low-impulsive rats. Combined with previous research, the authors suggest that cocaine use is predicted by and differently affects various aspects of impulsivity.

Finally, low-impulsive rats showed reduced frontal cortex regulation of behavior, leading to increased impulsivity.

Conclusions

“Our findings challenge the widely held view that impulsivity is a vulnerability factor for cocaine addiction.” in addition, the study reveals that rats with low impulsivity become more impulsive with chronic cocaine use.

This is associated with fewer DA receptors and decreased signaling in the pathways connecting the frontal cortex with the midbrain and limbic system.

The lack of higher regulatory control on midbrain and limbic system neural circuits promotes higher impulsivity.