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About 1.5 million Americans consume cocaine in a given year, according to the National Institute for Combating Drug Abuse. Many are regular users. Unfortunately, there is currently no FDA-approved drug treatment for cocaine addiction.
Behavioral therapy is the only treatment option for patients with cocaine dependence. Unfortunately, many treated patients remain likely to relapse when they are re-exposed to signals, such as specific settings or locations, that remind them of the drug's experience.
"If a cocaine addict who has a habit of taking cocaine in his sports car is following a behavioral therapy, it will be difficult to remove the signal from the sports car when he has finished his treatment. This can lead to a relapse, "he explains. Peter W. Kalivas, Ph.D., renowned drug researcher
Kalivas is a distinguished University Professor and Director of the Department of Neuroscience at the University of Medicine South Carolina (MUSC).
Kalivas and his colleagues report in the March 13, 2019 issue of Journal of Neuroscience that they have identified a type of neuron essential to cocaine-seeking behavior in rodents.
These neurons, known as the average spinous projection neurons expressing the dopamine D1 receptor (D1-MSN), are located in a well-known area of the reward system, the nucleus accumbens. The team also discovered that these neurons stimulate the drug search through their projections in a specific part of the brain, the ventral pallidum (VP).
The team includes lead author Jasper Heinsbroek, Ph.D., postdoctoral fellow at MUSC and Kalivas, and first author Thibaut Pardo-Garcia. Pardo-Garcia was a post-graduate student in the Kalivas Lab when the study was conducted and is currently a graduate student at the University of Michigan.
"It's sort of a breakthrough that Jasper has shown in a very definitive way that this ventral pallidum production is actually driving the drug-seeking behavior," says Kalivas.
D1-MSN coexist in the nucleus accumbens alongside another type of cell, the D2-MSN. Both cells play a critical role in the brain system by regulating goal-directed behavior. Objective-oriented behavior can be geared towards looking for shelter, looking for a partner or even becoming high. As such, the activity of D1-MSN could reinforce the behaviors likely to lead to a drug relapse, while D2-MSN could instead help to avoid these behaviors.
"There is a clear distinction between the function of these two types of neurons in the nucleus accumbens," says Heinsbroek.
"Increasing the activity of D1-MSN after drug use leads to greater motivation to seek drugs. Drug exposure reduces the ability of D2-MSN to limit motivation." excessive shelter in the presence of drug signals ".
To study how D1-MSN stimulates motivation to search for drugs, the MUSC team traced the connections of these neurons. They showed that individual neurons project on both the VP and another important area that regulates motivation, the ventral mesencephalon (VM).
To help determine whether the projection of VP or VM is responsible for the cocaine-seeking behavior, the researchers used a transgenic rat model provided by collaborators at the National Institute for Combating the Abuse of Cocaine. drug addicts. This animal model allowed the researchers to inhibit the activity of the D1-MSN and their projections on the VP compared to the VM.
The MUSC team found that cocaine research continued to exist when VM projections were inhibited. However, the inhibitory projections of PV strongly decreased the motivation to seek cocaine.
"These transgenic rats allowed us to specifically target D1-MSN projections using genetic technology," explains Heinsbroek. "Without them, it would not have been possible to identify the D1 projections to the vice president as important drivers of cocaine research."
These discoveries open a new avenue of research on cocaine addiction. They also point to new therapeutic targets that deserve further investigation. Kalivas and his laboratory wish to continue to explore the mechanisms underlying drug addiction, as they could, like these discoveries, be the key to future therapies.
"We need to find out how drugs modify the brain so that we can actually cure people with the disease," Kalivas said. "We have discovered a critical circuit in case of relapse and identified a specific target that we could potentially modify, modify and have a chance to cure addiction."
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