Rats on cocaine: When aversion is not enough

"Aversive cues matter from the very first exposure," Moschak said. 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 published this month in the journal Drug and Alcohol Dependence that describes a novel approach for rats to self-administer cocaine and encounter aversion from that very first "high."

The study found widely varying responses in rats, revealing that individual reactions to the unpleasant aspects of drug consumption 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 poking their nose 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 commonly used to impart the bitter flavor in tonic water. The study measured the rats' response to the mixed positive-negative experience of the cocaine and quinine and gauged whether their dislike of the quinine outweighed the impact of the cocaine.

After having the opportunity to self-administer the cocaine, Moschak said that three distinct patterns became evident among the rats. One group responded strongly to the quinine and stopped self-administering the cocaine entirely, which can be compared to the experience of a person who tries a drug, has a negative experience, and never does it again. A second group started off consuming the cocaine in low doses but gradually increased their consumption, indicating that the quinine did not deter them enough to stop. A third, unexpected group began the study with heavy cocaine consumption but then gradually leveled off.

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

While previous studies have explored the relationship between aversive cues and drug use, Moschak's research is the first to study them as a paired experience from the very first instance of drug use, he said.

"These findings could help explain why some individuals develop substance use disorders while others do not, and future studies may uncover genetic or neural differences that could guide targeted treatments," Moschak said.

The rats were taken off of the cocaine at the conclusion of the study and were unharmed by the experience, the team said. Future research will examine the brain regions in the rats that are active during drug use with an aversive cue and seek to understand the genetic or biological differences behind the rats' differing experiences.

"This is a fascinating study with great potential to help us better understand and address drug abuse in people," said Robert Kirken, Ph.D., dean of the College of Science. "With further study, this research could lead to better ways to prevent and treat addiction."

The cocaine used in the study was procured through the National Institute on Drug Abuse's Drug Supply Program, which supplies restricted substances for the purpose of research.