In a groundbreaking study, researchers at the University of Utah have successfully engineered fruit flies that can voluntarily consume cocaine, creating the first-ever fly model for cocaine addiction. Traditionally, fruit flies avoid cocaine due to its bitter taste, but by disabling their bitter-sensing receptors, scientists have been able to encourage addictive behavior within a mere 16 hours of exposure. This innovative model represents a major advancement in understanding the genetic and neurological mechanisms behind cocaine use disorder.
The researchers' new model showcases genetically altered fruit flies that will self-administer cocaine, effectively mimicking addictive behavior. By modifying the flies' taste receptors, the team enabled them to prefer cocaine-laced sugar water over plain sugar water. This significant finding has the potential to revolutionize the way researchers screen for addiction-related genes, allowing for rapid identification of effective treatment targets for individuals suffering from cocaine use disorder.
This model could prove invaluable in the development of new therapies aimed at preventing and treating cocaine use disorder, which currently affects approximately 1.5 million people across the United States. The hereditary nature of addiction complicates the identification of specific genes responsible for increasing the risk of developing cocaine use disorder. However, with this new fruit fly model, researchers aim to uncover the biological underpinnings of addiction and expedite the discovery of effective therapies.
Adrian Rothenfluh, PhD, associate professor of psychiatry at the University of Utah and senior author of the study, points out that flies and humans respond to cocaine in remarkably similar ways. “At low doses, they start running around, just like people,” Rothenfluh explains. “At very high doses, they become incapacitated, which is also true in humans.” With about 75% of the human genes associated with addiction found in fruit flies, these insects are critical for advancing our understanding of substance dependencies.
Despite their similarities, one significant difference remains: fruit flies typically do not like cocaine. Rothenfluh’s research team discovered that when given a choice between sugar water and cocaine-laced sugar water, flies consistently opted for the drug-free option, even after prior exposure to cocaine. To investigate the underlying reasons for this aversion, lead researcher Travis Philyaw, PhD, focused on the flies’ sense of taste, hypothesizing that their evolutionary adaptation to avoid plant toxins like cocaine might be at play.
Philyaw noted, “Insects are evolutionarily primed to avoid plant toxins, and cocaine is a plant toxin.” The researchers found that cocaine activates the bitter-sensing taste receptors located on the flies’ tarsal segments. By muting these bitter-sensing nerves, they allowed the flies to develop a preference for cocaine-laced sugar water, albeit at lower concentrations. Remarkably, the flies began to prefer the cocaine solution within just 16 hours of exposure.
The implications of this research are profound. With a new avenue for studying addiction in fruit flies, scientists can expedite the discovery of addiction-related genes. “We can scale research so quickly in flies,” Philyaw states. This rapid identification of risk genes may lead to breakthroughs in treatment targets for cocaine use disorder and other substance dependencies. Rothenfluh emphasizes the importance of understanding the mechanisms behind cocaine choice, noting that enhanced knowledge increases the chances of discovering effective therapies.
In addition to seeking specific therapeutics, Rothenfluh highlights the significance of basic research into the mechanisms of both human and fruit fly cognition. “Just trying to understand the simple little fly brain can give us insights that you cannot anticipate,” he remarks. This foundational research is crucial for uncovering unexpected yet impactful findings related to the human condition.
The research findings, titled “Bitter sensing protects Drosophila from developing experience-dependent cocaine consumption preference,” are published in the Journal of Neuroscience. The study was supported by various institutions, including the Huntsman Mental Health Institute and the National Institutes of Health.
This pioneering work on genetically modified fruit flies marks a significant milestone in addiction research. By creating a fruit fly model of cocaine use disorder, researchers hope to gain deeper insights into the biological mechanisms of addiction and develop effective treatments more rapidly.
