Scientists reveal individual nature of drug addiction in rats using cocaine for first time

A new study of rodents snorting laboratory-supplied cocaine reveals an interesting new perspective on how individuals respond differently when a reward is preceded by an unpleasant experience or aversive cues. Researchers at the University of Texas at El Paso (UTEP) hosted a biology lab version of an Oscars after-party for nearly 30 rodents, inviting the animals to stick their noses into a hole, which triggered an intravenous dose of cocaine and quinine hydrochloride through a previously inserted catheter. Quinine is a unique component of tonic water, and its bitter taste reaches the mice's bodies earlier than the bitter taste of cocaine.

Quinine is safe for rats and was chosen to mimic the aversive cues or unpleasant associations that first-time drug users might experience. In humans, these aversive cues include needle use and smoke inhalation. By looking at how mice process these negative and then positive stimuli, researchers gained fascinating new insights into an individual's vulnerability to addiction.

"Disgust cues are important from the first exposure," said Travis Moschak, a biologist at UTEP and lead author of the study.

Rats were given the opportunity to stick their noses into the "blow hole" and then receive an intravenous dose of quinine-cocaine, and during the experiment the rats displayed three distinct behavioral responses. One group (the "low consumption" group) was disturbed by quinine and stopped seeking cocaine altogether. The second group (the "ascending group") steadily increased their drug consumption through repeated use of quinine. To the scientists' surprise, the third group (the "down" group) initially binge-watched and showed stronger novelty-seeking behavior, but then quickly reduced their intake and showed the strongest aversive reactions to unpleasant stimuli.

The third group surprised us," Moschak said. "They seemed to be overindulging, a combination of too much cocaine and too much aversive stimulation. "

Interestingly, even after all rats completed the two-week trial and no longer had access to the drug, the rats in the rising group continued to seek out cocaine.

This study is the first to demonstrate how aversive cues and the experience of initiating drug exposure manifest themselves so differently in individuals. It provides keen insight into why some people can regulate drug use and even never touch drugs again after a first bad experience, while others become increasingly addicted despite negative cues tied to rewards.

The study also showed that even though all 27 rats were housed together and had equal access to self-injected cocaine, their behavior varied, and increasing exposure to quinine did not create consistent tolerance - something scientists had previously thought would occur.

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