PLOS One study: In adolescent lab animals exposed to cocaine, High-Intensity Interval Training boosts aversion to the drug

(Press-News.org) BUFFALO, N.Y. — People with substance use disorder who participate in recovery running programs have shown improved success in maintaining their sobriety and reducing their risk for relapse.

Those observations led Panayotis Thanos, a University at Buffalo neuroscientist who studies the brain’s reward system, to try to figure out the brain mechanisms behind that phenomenon.

In a new study published today in PLOS One, Thanos, PhD, senior research scientist in the Clinical and Research Institute on Addictions in the Jacobs School of Medicine and Biomedical Sciences at UB, and co-authors reveal that high-intensity interval training (HIIT) was more effective than moderate exercise in making adolescent lab animals avoid cocaine.

The researchers used adolescent lab animals because this is the age when most people who develop substance use disorder begin their exposure. The study focused on male rats only because previous observations have revealed some gender differences in drug-seeking behaviors between males and females. The researchers plan a future study on how HIIT affects females with regard to cocaine. 

HIIT as personalized medicine

“The study shows that HIIT exercise, rather than moderate exercise, during adolescence may protect against cocaine abuse,” says Thanos, a faculty member in the Department of Pharmacology and Toxicology in the Jacobs School. The findings provide evidence that HIIT could become a personalized medicine tool in drug abuse intervention.

“The key take-home is that not all exercise is created equal in terms of outcome,” Thanos says. “Exercise is not a binary therapeutic tool but rather we need to think about exercise as dose-dependent, the way we think of medicine as dose-dependent.”

In the study, rats exposed to HIIT exercise on a treadmill were compared to rats exposed to moderate treadmill exercise. Both groups then underwent a behavioral test called cocaine place preference, which trains the animal to discriminate between two chambers: one where they can access cocaine and one where they can access saline. Cocaine preference is when the animal spends more time in the cocaine chamber, while cocaine aversion is when the animal chooses to spend more time in the saline chamber.

The findings were significant, Thanos explains, because not only did the HIIT animals exhibit a preference for the saline chamber, they exhibited a clear aversion to the cocaine chamber.

Increase in a molecular switch for addiction

“We believe that the increase in aversion to cocaine happens in the HIIT animals,” Thanos says, “because of this exercise dose-dependent effect on the brain’s reward circuit that involves an increase we observed in ΔFosB.” ΔFosB is a transcription factor commonly referred to as a molecular switch for addiction and known to boost sensitivity to drugs of abuse. “Our study showed that HIIT increased ΔFosB levels causing an aversion to consuming cocaine,” he adds.

The findings reveal new avenues that Thanos and his colleagues plan to explore, including how HIIT may affect brain metabolism.

“We know from recent studies in our lab with steady, moderate treadmill running that compared to sedentary animals, exercise decreased metabolism in the somatosensory cortex of the brain while activating other brain regions involved in planning and decision,” he says. “That activation may help dampen various aspects of cocaine abuse and relapse.”

The paper also discusses the need to better understand gender differences in preference for cocaine. “Future studies need to explore how HIIT affects cocaine preference in female rats,” Thanos says, adding that the literature in the field includes evidence that females seem to be more vulnerable to certain phases of addiction.

UB co-authors are Teresa Quattin, MD, UB Distinguished Professor in the Department of Pediatrics and senior associate dean for research integration in the Jacobs School; Nikki Hammond, a former graduate student; and Nabeel Rahman and Sam Zhan, former undergraduate students in Thanos’ lab. Other co-authors are from Washington University School of Medicine and Western University of Health Sciences.

The study was supported by the SUNY Research Foundation (RIAQ0940).

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