For more than 50 years, the conventional wisdom in the field of research in cocaine use has been that people take cocaine based on the theory of the drug providing positive reinforcement to the user.
New research out of the University of Cincinnati shows that a pharmacological equation disproves that concept and could spark a major shift in that field of research.
The study was published in the journal Scientific Reports.
Andrew Norman, PhD, professor in the Department of Pharmacology and Systems Physiology at the UC College of Medicine and corresponding author of the study, says that in 1968, the first paper on cocaine self-administration was published showing that it was an example of operant behavior theory, a method of learning that uses rewards and punishment to modify behavior. It suggests that certain things like food or drugs motivate the behavior according to schedules of reinforcement.
"The theory maintains that the more reinforcing a drug is, the faster users take it," Norman says. "Interestingly, animals that self-administer cocaine slow down intake as doses get higher, implying that higher doses are less reinforcing, which doesn't make sense. But at really lower unit doses, the actual number of presses the animal does goes up as you increase the dose."
"As pharmacologists, we know that drug effects are related to concentration," adds Norman. "The first question a pharmacologist asks is what is the response that is being induced by this drug. In our case, it's the lever pressing behavior. Our big innovation with this latest research is that we calculated what the concentration of cocaine is in the body every second of the session. What we show is that there is a range of cocaine concentrations that drive the behavior."
"We are hoping that it will open up everyone else's eyes to what's actually been seen for multiple decades now," Tron Esqueda says. "It will hopefully start shifting the current idea on how to study cocaine addiction into a newer idea."
"I think it's going to be a paradigm shift of how to approach preclinical cocaine self-administration studies in animal models," Desai says. "This will hopefully be an example of how to design experiments and interpret data appropriately so that the knowledge can be applied to cocaine use in humans."
Desai, who was an undergraduate neuroscience student in the UC College of Arts & Sciences when she joined the Norman lab, says this project has shifted her career goal from being a medical docdtor to enrolling in the combined research-directed MD/PhD program in the UC College of Medicine.
"This is my first research experience," she says. "UC is a top research university and there is really good mentorship, good resources and the research we do here is top level."
All photos/Andrew Higley/UC Marketing + Brand
