UC San Diego School of Medicine and Salk Institute for Biological Studies researchers have created an atlas of the amygdala, a structure within the brain that plays a crucial role in controlling emotional responses to drugs, it was announced Thursday.
Their findings, published Thursday in Nature Neuroscience, helped the researchers identify a potential new treatment for cocaine addiction -- something poorly understood at the molecular level and with virtually no approved pharmacological treatments.
"There are some drugs that can help treat other addictions, such as those to opioids or nicotine, but there are currently no safe and effective drugs approved for cocaine addictions," said co-senior author Francesca Telese, an associate professor in the Department of Psychiatry at UCSD School of Medicine. "These findings help address that problem and could also point to universal molecular mechanisms of addiction that we haven't understood until now."
According to the National Institute on Drug Abuse, an estimated 4.8 million people used cocaine in 2021, while only 1.4 million people had a cocaine use disorder.
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"Some people use cocaine recreationally and never develop an addiction, while others are extremely susceptible to addiction after very little exposure to the drug or may relapse even after years of abstinence," Telese said. "Our long-term goal is to understand why there are these inter-individual differences in drug addiction behavior."
The researchers studied brain samples from rats that had been allowed to self-administer cocaine for an extended period before being cut off from the drug for a period of abstinence, a university statement read. These samples were obtained from the cocaine brain bank at UC San Diego.
"The cocaine brain bank is an exceptional resource and was invaluable for this study because it allowed us to study a cohort of rats with a large amount of genetic variety, which mimics the diversity we see in human populations," Telese said. "Further, using a model of cocaine addiction where rats administered the drug to themselves let us look at the connection between our molecular discoveries and actual addiction behaviors."
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The team determined what genes were expressed in individual cells from the rats' amygdala, a part of the brain that is central to processing emotions and is highly active in people with addictions.
According to a university statement, to make sense of the large amount of data generated through their sequencing experiments, Telese collaborated with bioinformatics expert and co-senior author Graham McVicker, an associate professor at the Salk Institute of Biological Studies and an assistant adjunct professor in the Department of Cellular & Molecular Medicine at UCSD School of Medicine.
Jess Zhou, a UCSD graduate student working with McVicker, developed the workflow needed to assemble their sequencing data into a molecular atlas of the rat amygdala, the statement read.
In addition to identifying molecular factors that influence cocaine addiction behaviors, the researchers were able to test a drug in the rats that "helped reverse these behaviors by targeting an enzyme involved in both energy metabolism and signaling between neurons."
The researchers are now working on larger sample-size studies that can help determine how much of the effects they observed were based on preexisting genetics in the rats and how much were based on responses to extensive cocaine usage.
"This research suggests that preexisting genetics may play a much bigger role in addiction than we've previously understood," said Telese. "Unraveling these genetics will be key to improving personalized medicine for addictions. If we don't understand the risk of relapse in individual people, we can*t fully understand the disease."
