You may be surprised to learn that, according to AddictionHelp.com, an estimated 12 percent of American adults (~41 million) have used powder cocaine in their lifetimes. Thankfully, not everyone who partakes develops an addiction, but for the over 50 million Americans who had a cocaine use disorder in the previous year, medical approaches to overcoming addiction are much needed.
Addiction research provides the best chance at developing effective treatments. However, in the case of cocaine use disorder, research has typically relied on intravenous drug self-administration animal models. In other words, the observed animals have an implanted IV catheter they can use to self-dose with a drug, but despite its historical usefulness, the method has some significant drawbacks.
The lab of Cody Siciliano, assistant professor of pharmacology, has devised a new method that overcomes the limitations of IV drug self-administration and that more closely mimics cocaine use in humans: intranasal administration. The research was published in Nature Communications in December 2025 and was selected by the editors as one of the top recent papers in the journal.
We touched base with Siciliano, who gave us the scoop on his latest work.
What issue/problem does your research address?
Intravenous drug self-administration has long been a cornerstone method in behavioral neuroscience for modeling addiction and studying motivation and decision making. However, this approach is technically demanding, requires surgical implantation, and often results in high attrition rates. We sought to overcome these limitations by developing a model that more closely mirrors how humans typically initiate narcotic use: through intranasal insufflation or “snorting.”
This work establishes the first non-human model of intranasal cocaine self-administration, providing a technically accessible and translationally relevant platform to study the neural mechanisms underlying cocaine use disorder.
What was unique about your approach to the research?
We developed a completely new method that allowed mice to voluntarily self-administer cocaine intranasally without the need for intravenous catheters or invasive surgical implants. This paradigm overcomes long-standing technical barriers in addiction research and better models how humans typically use cocaine.
The work was made possible by Vanderbilt’s highly collaborative environment, which integrates behavioral neuroscience with advanced analytical and pathological expertise. The Vanderbilt Mass Spectrometry Core Laboratory enabled precise quantification of plasma cocaine levels, while the Translational Pathology Shared Resource performed detailed histopathological analyses confirming the safety of the intranasal procedure.
What were your top findings?
We found that mice will voluntarily take cocaine through the nose, demonstrating for the first time that intranasal drug self-administration is possible in a non-human animal. This behavior was reliable, dose-dependent, and produced blood drug levels comparable to those seen in human cocaine use.
We also confirmed that the delivery method was safe and caused no lung damage. These findings establish a powerful new tool for studying the brain mechanisms that drive cocaine use and addiction. Because this model closely mirrors how people commonly take cocaine, it provides a more realistic and translational foundation for developing and testing new treatments for substance use disorders.
What do you hope will be achieved with the research results on the short term?
This approach opens new opportunities for researchers beyond the addiction field to leverage the reinforcing properties of drugs to study motivated behavior more broadly, echoing practices from early behavioral neuroscience. With its enhanced validity and greatly improved ease of use, this technique has the potential to drive a major paradigm shift in the field, which hasn’t seen a paradigm-shifting technical advance in well over half a century.
Where is this research taking you next? What will you personally be doing, or how will other researchers build on this work?
Next, we are expanding this work by combining the intranasal self-administration model with advanced neuroimaging approaches to visualize neuronal activity during drug-taking behavior. Although the procedure requires a head bar for restraint, it remains fully compatible with cutting-edge techniques such as multiphoton imaging, fiber photometry, and virtual reality–based behavioral paradigms. We are also working to validate the approach in female mice to enhance its translational relevance. This model provides a powerful framework for linking motivated drug use with real-time neural activity, offering new opportunities to study the circuitry underlying reinforcement and decision-making.
Go deeper
The paper “Intranasal cocaine self-administration in male mice” was published in Nature Communications in December 2025.
Funding
This research used funds from the National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, the Alkermes Pathways Research Award, the Brain Research Foundation, the Whitehall Foundation, the W.M. Keck Foundation, and the Vanderbilt University Stanley Cohen Innovation Fund.