The tendency to addiction begins with the first experience with drug use

EL PASO, Texas (December 3, 2024) – The use of addictive substances is often accompanied by an unpleasant experience, such as using a needle, ingesting a bitter substance or inhaling smoke. These unpleasant experiences — known as aversive signals — and our initial reactions to them are crucial to understanding who becomes addicted, said biologist Travis Moschak, Ph.D. from the University of Texas at El Paso.

UTEP biologist Travis Moschak, Ph.D., supervises a student working in his laboratory in the Biological Sciences Department. Moschak is lead author of a new study that finds that individual reactions to the unpleasant aspects of drug use may be important in determining susceptibility to addiction. Photo credit: The University of Texas at El Paso

“Aversive signals are important from the first touch,” said Moschak. But until now, he said, there hasn’t been a good animal model to study this concept.

Moschak is the lead author of a new study in the journal Drug and alcohol addiction This describes a novel approach for rats to self-administer cocaine and be met with aversion from the first “high.”

The study found very different responses in rats and showed that individual reactions to the unpleasant aspects of drug use can be important in determining susceptibility to addiction.

Moschak explained that nearly 30 rats were given the opportunity to self-administer small doses of cocaine by sticking their noses into a designated hole. Each dose of cocaine was preceded by a small, bitter-tasting dose of quinine, a substance that is safe for rats and is often used to give tonic water its bitter taste. The study measured the rats’ response to the mixed positive-negative experience with cocaine and quinine and determined whether their aversion to the quinine outweighed the effects of the cocaine.

After Moschak had the opportunity to administer the cocaine himself, three different patterns became apparent in the rats. One group reacted strongly to the quinine and stopped self-administering cocaine altogether, which can be compared to the experience of a person who tries a drug, has a negative experience, and never uses it again. A second group began using cocaine in low doses but gradually increased their use, suggesting that the quinine did not sufficiently deter them from quitting. A third, unexpected group began the study with heavy cocaine use but then gradually tapered off.

“The third group surprised us,” said Moschak. “They seemed to have consumed too much and the combination of too much cocaine and too much aversive stimulus took over.”

While previous studies have examined the connection between aversive stimuli and drug use, Moschak’s research is the first to examine them as a paired experience from the very first instance of drug use, he said.

“These results could help explain why some people develop substance use disorders but others do not, and future studies could uncover genetic or neural differences that could guide targeted treatments,” Moschak said.

The rats were withdrawn from cocaine at the end of the study and remained unharmed by the experience, the team said. Future research will examine the rats’ brain regions that are active during drug use with an aversive stimulus and attempt to understand the genetic or biological differences behind the rats’ different experiences.

“This is a fascinating study with great potential to help us better understand and combat drug abuse in humans,” said Robert Kirken, Ph.D., dean of the College of Science. “With further study, this research could lead to better options for addiction prevention and treatment.”

The cocaine used in the study was obtained through the National Institute on Drug Abuse’s Drug Supply Program, which supplies restricted substances for research purposes.

About the University of Texas at El Paso

The University of Texas at El Paso is America’s leading Hispanic university. Located at the westernmost tip of Texas, where three states and two countries converge along the Rio Grande, 84% of our 25,000 students are Hispanic and more than half are the first in their family to attend college. UTEP offers 170 bachelor’s, master’s and doctoral degree programs at the only open-access, top research university in America.

Last updated on December 3, 2024 at 12:00 am | Originally published December 3, 2024

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