Nav: Home

Brain research reveals a circuit for cocaine relapse

March 18, 2019

Approximately 1.5 million Americans use cocaine in a given year, according to the National Institute on Drug Abuse. Many are repeat users. Unfortunately, there are currently no FDA-approved medicinal treatments for cocaine addiction.

Behavioral therapy is the only treatment option for patients with cocaine addiction. Unfortunately, many treated patients remain susceptible to relapse when re-exposed to cues, such as settings or specific places, which remind them of the drug experience.

"If a cocaine addict who is used to doing cocaine in his or her sports car goes through behavioral therapy, it will be difficult to remove the cue of the sports car when he or she finishes therapy. That can result in a relapse," explains noted addiction researcher Peter W. Kalivas, Ph.D.

Kalivas is a distinguished university professor and chair of the Department of Neuroscience at the Medical University of South Carolina (MUSC).

Kalivas and his colleagues report in the March 13, 2019 issue of the Journal of Neuroscience that they have identified a type of neuron that is critical for cocaine-seeking behaviors in rodents.

These neurons, known as dopamine D1 receptor-expressing medium spiny projection neurons (D1-MSNs), are located in a well-known area of the reward system, the nucleus accumbens. The team also discovered that these neurons drive drug seeking through their projections to a specific part of the brain, the ventral pallidum (VP).

The team includes senior author Jasper Heinsbroek, Ph.D., a postdoctoral scholar at MUSC working with Kalivas, and first author Thibaut Pardo-Garcia. Pardo-Garcia was a post-baccalaureate student in the Kalivas laboratory when the study was conducted and is currently a graduate student at the University of Michigan.

"It's kind of a breakthrough that Jasper has shown very definitively that this ventral pallidum output is actually carrying the drive to engage in the drug-seeking behavior," explains Kalivas.

D1-MSN co-exist in the nucleus accumbens alongside another cell-type, the D2-MSNs. Both cells play a critical role in the brain system that regulates goal-directed behavior. Goal-directed behavior can be geared towards looking for shelter, finding a mate, or even getting high. As such, D1-MSNs activity could reinforce behaviors that would lead to drug relapse, while D2-MSNs instead may help avert these behaviors.

"There is a clear distinction between the function of these two types of neurons within the nucleus accumbens," explains Heinsbroek.

"Increased activity of D1-MSNs after drug use leads to higher motivation to seek drugs. Exposure to drugs reduces the capacity of D2-MSNs to limit excessive motivation. This can lead to a strong drive to seek drugs over natural rewards such as food and shelter in the presence of drug cues."

To investigate how D1-MSNs drive the motivation to seek drugs, the MUSC team traced the connections of these neurons. They showed that individual neurons project to both the VP and another major area that regulates motivation, the ventral mesencephalon (VM).

To help identify whether the VP or VM projection is responsible for cocaine-seeking behavior, the researchers used a transgenic rat model provided by collaborators at the National Institute of Drug Abuse. This animal model allowed the researchers to inhibit the activity of D1-MSNs and their projections to the VP versus the VM.

The MUSC team found that cocaine seeking continued to exist when the VM projections were inhibited. However, inhibiting projections to the VP strongly diminished the motivation to seek cocaine.

"These transgenic rats allowed us to specifically target the projections of D1-MSNs using genetic technology," explains Heinsbroek. "Without them, identifying D1 projections to the VP as important drivers of cocaine seeking would not have been possible."

These findings open a new avenue of research into cocaine addiction. They also point to novel therapeutic targets that merit further investigation. Kalivas and his laboratory aim to continue to explore the mechanisms that underlie drug addiction because, as with these findings, they could hold the key to future therapies.

"We need to find out how drugs change the brain so that we can actually cure people who are afflicted," says Kalivas. "We have discovered a circuit that is critical for relapse and identified a specific target, which we could potentially go in and modify and have a chance at curing addiction."
-end-
About MUSC

Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion. MUSC operates a 700-bed medical center, which includes a nationally recognized Children's Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute-designated center) Level I Trauma Center, and Institute of Psychiatry. For more information on academic programs or clinical services, visit musc.edu. For more information on hospital patient services, visit muschealth.org.

Medical University of South Carolina

Related Neurons Articles:

New tool to identify and control neurons
One of the big challenges in the Neuroscience field is to understand how connections and communications trigger our behavior.
Neurons that regenerate, neurons that die
In a new study published in Neuron, investigators report on a transcription factor that they have found that can help certain neurons regenerate, while simultaneously killing others.
How neurons use crowdsourcing to make decisions
When many individual neurons collect data, how do they reach a unanimous decision?
Neurons can learn temporal patterns
Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals.
A turbo engine for tracing neurons
Putting a turbo engine into an old car gives it an entirely new life -- suddenly it can go further, faster.
Brain neurons help keep track of time
Turning the theory of how the human brain perceives time on its head, a novel analysis in mice reveals that dopamine neuron activity plays a key role in judgment of time, slowing down the internal clock.
During infancy, neurons are still finding their places
Researchers have identified a large population of previously unrecognized young neurons that migrate in the human brain during the first few months of life, contributing to the expansion of the frontal lobe, a region important for social behavior and executive function.
How many types of neurons are there in the brain?
For decades, scientists have struggled to develop a comprehensive census of cell types in the brain.
Molecular body guards for neurons
In the brain, patterns of neural activity are perfectly balanced.
Engineering researchers use laser to 'weld' neurons
University of Alberta researchers have developed a method of connecting neurons, using ultrashort laser pulses -- a breakthrough technique that opens the door to new medical research and treatment opportunities.

Related Neurons Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".