Georgia: Amphetamine may slow down the rise of temperature in the body and mask fatigue, which could allow athletes to run significantly longer but result in potentially dangerous overheating of muscles, according to a study. Researchers at Georgia State University and Indiana University have identified a new mechanism underlying the physical performance enhancement effect of amphetamine, providing new arguments about the potential danger of using psychostimulants to improve performance during exercise. The findings are published in the journal Physiological Reports.
The study found that rats treated with amphetamine (2 mg/kg) were
able to run significantly longer on a treadmill than the control group.
The researchers used a mathematical model to explain the
amphetamine-induced changes in body temperature and calculate parameters
that are difficult to measure experimentally. They suggest amphetamine
may mask or delay fatigue by increasing heat dissipation (such as
evaporative cooling through sweating in humans) and postponing when core
body temperature exceeds the exhaustion threshold, which significantly
increases muscle temperature by the end of the run and could pose health
“Rats injected with amphetamine spent as much energy to run and
processed oxygen the same as those that were not injected,” said Dr.
Yaroslav Molkov, associate professor in the Department of Mathematics
and Statistics at Georgia State, previously of Indiana University-Purdue
University Indianapolis. “But what was significantly different was
their body temperature. In rats that received amphetamine, their body
temperature was lower. When normal rats start running, their temperature
starts rising and at some point when it hits a certain level, they
stop. There’s a very strong signal from the brain to not overheat.
However, if the temperature increases more slowly, it hits the same
level later and that’s why rats treated with amphetamine are able to run
“Using mathematical modeling, we were able to prove that what happens
is they increase their heat exchange with the environment. Basically,
they increase their heat dissipation. But while heat dissipates quicker
from the core body, it’s not the same for muscles. Your body is tuned to
know that if the core temperature, and hence, the muscle temperature
reach certain levels, you should stop. But when you inject yourself with
amphetamine, you don’t know that anymore because your temperature
control system is tricked and you think that it’s not time to stop yet
because your core temperature is not that high, even though your muscle
temperature can already be dangerously high. I think this is one of the
most important conclusions of this paper, that a seemingly innocent
mechanism that accounts for better performance and durability actually
turns out to be really dangerous as far as muscle overheating is
Exhaustion serves as an important safety mechanism to keep organisms
from irreversible damage caused by intense exercise. Previous studies
have shown that low to moderate doses of amphetamine increase the time
until exhaustion. Amphetamine use is prohibited during competitions, but
athletes may use amphetamine to improve their performance in some
situations by delaying exhaustion. The mechanism by which amphetamine
increases the time to exhaustion is unknown.
High body temperature is a major signal of exhaustion. During
exercise, increased heat production in the muscles raises the
temperature of muscles and the core body temperature. Regulatory heat
dissipation mechanisms, such as vasodilation and evaporative cooling
through sweating in humans, help remove heat and limit temperature
growth during exercise. A balance between heat production and heat
dissipation is crucial for keeping the temperature in different parts of
the body in a safe range.
In this study, researchers wanted to investigate the effect of
amphetamine on the thermoregulatory system. They measured core body
temperature and oxygen consumption of rats (control group and
amphetamine-treated group) running on a treadmill with incrementally
increasing speed and incline.
Rats treated with amphetamine (2 mg/kg) were able to run
significantly longer than control rats. This amount of amphetamine
slowed down temperature rise, decreasing core body temperature in the
beginning of the run without affecting oxygen consumption. The control
rats showed a steady increase in body temperature, and a lower dose of
amphetamine (1 mg/kg) had no effect on core body temperature or oxygen
Researchers designed a mathematical model to estimate physiological
parameters affected by amphetamine that are difficult to measure
experimentally. Modeling revealed that administering amphetamine
increases heat dissipation in the core and predicted that muscle
temperature at the end of the run was significantly higher (almost one
degree higher) for the amphetamine-treated group.
The researchers found the mechanism underlying the physical
performance enhancement effect of amphetamine affects the
thermoregulatory system and could result in potentially dangerous
overheating of muscles. They conclude that while amphetamine improves
endurance and extends the time at which exhaustion occurs, its use can
result in health-threatening complications.
Collaborators for the study include Dmitry Zaretsky, Daniel Rusyniak
and Maria Zaretskaia of Indiana University School of Medicine;
Abolhassan Behrouzvaziri and Yeonjoo Yoo of Indiana University-Purdue
University Indianapolis; and Ekaterina Morozova of Indiana University.
The study was funded by the National Institute on Drug Abuse and Purdue Research Foundation.