Researchers study cocaine addiction in rats

Under the right circumstances, even rats can become cocaine addicts.

But a study by Pitt researchers could help humans and rats alike kick their habits.

Dr. Yan Dong, a Pitt neuroscience professor, led a team of neuroscience researchers on a project that began in 2009 to silence the synapses, or connections between neurons in the brain, that trigger cocaine cravings in former users. The team studied the effects of cocaine addiction and withdrawal in rats and then identified specific brain receptors that they could modify with pharmaceuticals to prevent cocaine relapse in humans. The team plans to use its findings to produce a pill that will weaken synapses in the brain, but have not determined a date for production.

Nature Neuroscience published the findings in its November 2013 issue. 

Grants from the National Institute of Health and the German Research Foundation funded the research.

Because the brain processes associated with addiction are similar in humans and rodents, the researchers decided to study rats. 

Although the cognition and reasoning abilities of rodent and human brains differ greatly, Brian Lee, a scientist at the Allen Institute for Brain Science in Seattle who collaborated on the project, said the pleasure-seeking center in both brains is similar. 

According to Dong, when someone stops using a substance he or she is addicted to, the nucleus accumbens — a small area of the brain that controls emotions and motivation — creates synapses that stimulate cravings. 

“After they [addicts] stay away from drugs, they appear to be doing OK in the beginning,” Dong said. “The urge does not diminish, but becomes stronger and stronger. If we can prevent this increase, we can reduce the chance for drug addicts to relapse.”

During the experiment, researchers trained rodents to inject themselves with a 0.75 mg/kg per 0.1 mL infusion of cocaine by pressing a button. Each day, the rodents pressed the button and received the dose until the researchers stopped giving them the drug. 

Researchers discovered that the physical pleasure experienced after drug use is similar in both animals. 

Dong said after the rodents stopped taking the drug, they showed increased heart rate and symptoms of depression, which are the same withdrawal symptoms found in humans. 

“We know that humans, once exposed to drugs, are normally rewarded,” Dong said. “And it’s actually common for all species. These rodents, they like drugs. The cravings start [on] day one.”

Dong said that although cravings for cocaine appear immediately after a user stops taking the drug, the brain synapses for cravings are weak in the initial period after quitting. 

He added that humans experience the strongest cravings about one year after stopping cocaine use. But rodents, which have a lifespan of two years, experience cravings after one week.

Several factors contribute to drug relapse, which is fueled by the cravings. 

Yavin Shaham, a senior investigator for the National Institute on Drug Abuse’s Intramural Research Program who collaborated on Dong’s study, said levels of stress and exposure to drugs influence the likelihood of a relapse. 

“Three common factors that contribute to relapse in humans, and can be studied in rodent models, are exposure to stress and drug cues and acute exposure to the previously abused drugs,” he said.

Drug cues include locations or settings with which drug use is associated and the presence of others using the drug. Both Shaham and Dong stressed that scenarios such as these can produce the strongest cravings.

Both Shaham and Dong said they believe their findings in rodents will translate well to humans. 

But Dong said plans to test similar research on humans are still “a long shot,” but he hopes to expand the study beyond cocaine usage. 

Susan Sesack, a Pitt neuroscience professor, and Eric Nestler, director of the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai, as well as several other researchers, worked on the study with Dong, Lee and Shaham.

Sesack and Nestler did not respond to request for comment. 

For Lee, the study of addiction is fascinating because of addiction’s enduring nature. 

“Drug addiction is an extremely disruptive brain pathology,” Lee said. “Not only is it a financial burden to the individual and society, [but] it destroys families, and this is what motivates me to try and find a cure.”