Last year, more than 60,000 Americans died of an opioid overdose, and millions more struggled with opioid and cocaine addiction. To get to the roots of why some people are more prone to drug addiction than others, researchers at The Scripps Research Institute are launching a pair of studies on genetic factors behind oxycodone and cocaine addiction and treatment.
In support of the research, the National Institute of Health's National Institute on Drug Abuse (NIDA) has awarded the Scripps Research team two separate grants totaling $7.5 million. The five-year grants will allow the researchers, led by Olivier George, PhD, associate professor in the Department of Neuroscience at Scripps Research, to combine next-generation sequencing with state-of-the-art behavioral screening in a unique, genetically diverse, nonhuman animal model of drug addiction, and screen genetically diverse rats for their propensity for drug addiction and create shared tissue banks for researchers around the world to use in addiction studies.
For the studies, George's group is collaborating with the lab of Leah Catherine Solberg Woods, PhD, at Wake Forest University, who will breed the rats, and the lab of Abraham Palmer, PhD, at the University of California, San Diego, who will genotype the animals. The behavioral testing and biobanking will be completed at Scripps Research.
"The big questions right now are what the genetic mechanism is that makes someone vulnerable to drug addiction, and why one medication works for someone, but not someone else," says George. "It's hard to study that in humans because individuals are also exposed to such different environments, which bias the results."
Rodent studies have also been limited, George says, because most labs use strains of rodents with little variation in their genetics between individual animals. This makes it hard to find animals with drastically different genetic and behavioral profiles. In addition, rodent studies usually rely on a few dozen animals at most, since screening each animal's behavior is so labor intensive. But armed with the new grants, George's team will study about around 2,500 genetically different rats.
"Scripps Research is one of the only places in the world where you can do this type of large-scale behavioral study because of the equipment, expertise, and resources we have," George says. "There is an amazing team of people here."
The rats in the new studies are a good model for the genetic diversity of the human population because they were created by cross-breeding many different strains, George says. "They are not your typical albino laboratory rats. They vary in their color, size, appetite, anxiety levels, memory skills, and now we have evidence that they also vary in their addiction tendencies," he adds.
In addition to screening the rats for compulsive drug use and addiction-related behaviors, George's group will study whether genetic variation affects how individuals respond to current medications used to treat addiction. The collaboration with the Palmer lab, which will perform the genotyping, will then allow the team to identify gene variants that may predict the vulnerability to addiction or the efficacy of a given medication.
The animals will have access to either cocaine or oxycodone for 6 to 12 hours a day-;a much longer time period than most rat studies-;so that drug use leads to the same set of negative symptoms and compulsive-like behaviors seen in humans.
The team plans to collect samples from the animals-;including blood, urine, feces, a variety of organs and even blood cells capable of producing stem cells-;and save them in two tissue banks, dubbed the CocaineBiobank and OxycodoneBiobank. Researchers from other institutions will then be able to access the samples, and the corresponding genetic information and behavioral results, to launch their own studies on addiction. For instance, George imagines microbiome researchers using the feces samples to correlate bacteria in the rats' guts with their addiction propensity.
"The reception from the community has been fantastic already. We have just started the research, and we already have a lot of requests for samples," says George.