Summary: A new study finds that high-intensity interval training (HIIT) during adolescence is more effective than moderate exercise at reducing cocaine-seeking behavior in lab animals. Animals exposed to HIIT developed a preference for non-drug environments and showed aversion to cocaine exposure. These behavioral changes were linked to an increase in ΔFosB, a transcription factor associated with addiction-related neural plasticity.
The results highlight that exercise intensity matters for shaping the brain’s reward circuits and its response to drugs. These findings could guide more targeted use of structured exercise as a preventive or therapeutic tool for substance use disorders.
Key Facts
- HIIT impact: High-intensity interval exercise produced cocaine avoidance and increased time spent in non-drug environments.
- Molecular mechanism: HIIT raised brain levels of ΔFosB, a molecular regulator linked to addiction pathways.
- Personalized tool: Exercise may act as a dose-dependent intervention for preventing or reducing drug abuse risk.
Source: University at Buffalo
Context: Recovery running and other structured exercise programs have been associated with improved outcomes for people in addiction recovery, including reduced relapse rates. Motivated by these clinical observations, Panayotis Thanos and colleagues investigated how specific exercise regimens affect the adolescent brain’s response to cocaine.
In a study published in PLOS One, Panayotis Thanos, PhD, senior research scientist at the Clinical and Research Institute on Addictions in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, and co-authors compared the effects of chronic HIIT versus moderate treadmill running on cocaine conditioned place preference in adolescent male rats.
The researchers selected adolescent male rats because adolescence is a critical period when many humans first experiment with substances, and prior work has shown sex differences in drug-seeking behaviors. The team notes that follow-up studies will examine how HIIT affects female subjects.
HIIT as personalized medicine
“Our study suggests that HIIT during adolescence may provide a protective effect against cocaine abuse,” says Thanos, who is on the faculty of the Department of Pharmacology and Toxicology. The data support the idea that exercise should be considered in a dose-dependent way—similar to medication dosing—rather than as a single, uniform therapy.
In the experiment, one group of rats performed HIIT on a treadmill and another group performed moderate treadmill exercise. After six weeks of their respective exercise programs, both groups underwent a conditioned place preference (CPP) test. CPP measures whether an animal prefers a chamber previously paired with cocaine versus a chamber paired with saline. Spending more time in the cocaine-paired chamber indicates drug preference; more time in the saline chamber indicates aversion.
Rats that completed the HIIT protocol not only showed reduced preference for the cocaine chamber, they displayed a clear aversion—choosing the saline chamber over the cocaine-paired environment. This behavioral shift was significantly different from sedentary controls and from rats exposed to moderate exercise.
ΔFosB and the brain’s reward circuitry
The authors measured brain levels of ΔFosB after behavioral testing and found a marked increase in the striatum of HIIT animals. ΔFosB is a transcription factor often described as a molecular switch in addiction-related neuroplasticity; it modulates gene expression in reward pathways and can alter sensitivity to drugs of abuse.
Thanos and colleagues propose that the elevation of ΔFosB following HIIT contributes to the observed cocaine aversion. While ΔFosB has been linked to increased sensitivity in some contexts, this study indicates a complex, dose-dependent interaction between exercise intensity, molecular signaling, and drug-related behavior that may produce protective effects under certain conditions.
The team also plans to investigate how HIIT influences brain metabolism and activity across regions involved in planning, decision-making, and sensory processing. Prior work from the lab showed that moderate treadmill running altered metabolic activity in the somatosensory cortex and other regions, potentially contributing to reduced drug-seeking and relapse vulnerability.
The paper emphasizes the need to understand sex differences in exercise-related protection against substance use, noting evidence that females can be more vulnerable during certain addiction phases and that future studies should directly assess HIIT’s effects in female animals.
Co-authors from the University at Buffalo include Teresa Quattin, MD; Nikki Hammond; and former undergraduate researchers Nabeel Rahman and Sam Zhan. Additional collaborators are affiliated with Washington University School of Medicine and Western University of Health Sciences.
Funding: The study was supported by the SUNY Research Foundation (RIAQ0940).
About this exercise and addiction research news
Author: Ellen Goldbaum
Source: University at Buffalo
Contact: Ellen Goldbaum – University at Buffalo
Image: Image credited to Neuroscience News
Original Research: Open access. “Chronic High Intensity Interval Training (HIIT) exercise in adolescent rats result in cocaine place aversion and ΔFosB induction” by Panayotis Thanos et al. (PLOS One). DOI: 10.1371/journal.pone.0316228
Abstract
Chronic High Intensity Interval Training (HIIT) exercise in adolescent rats results in cocaine place aversion and ΔFosB induction
High-Intensity Interval Training (HIIT) has become widely popular for its health benefits. Like other forms of exercise, HIIT might help prevent substance use, but its specific impact on the reinforcing effects of drugs during adolescence has been underexplored.
This study assessed the effects of adolescent HIIT on cocaine conditioned place preference (CPP) in male Lewis rats. The HIIT protocol consisted of daily 30-minute treadmill sessions (ten 3-minute intervals) over six weeks, with progressive speed increases up to 0.8 mph (21.5 m/min). Sedentary rats remained in their home cages, while another comparison group completed moderate treadmill exercise.
After six weeks, rats underwent CPP testing with cocaine (25 mg/kg), and brain levels of ΔFosB were measured post-behavior. HIIT rats spent significantly less time in the cocaine-associated chamber (a 19% reduction in place preference compared to sedentary controls) and exhibited a pronounced aversion to the cocaine-paired environment. HIIT also produced a substantial (65%) increase in striatal ΔFosB relative to sedentary animals.
These results suggest that adolescent HIIT may protect against cocaine abuse, potentially through ΔFosB-mediated changes in reward circuitry. The findings have clinical implications for exercise-based strategies to reduce substance misuse risk. Future studies will explore HIIT’s effects in females and investigate the underlying neural mechanisms.