Brain and Body

Scientists Discovered a Brain Mechanism That Could Be Targeted to Treat Cocaine Addiction

May 24, 2016 | Kelly Tatera

Cocaine powder and a razor blade
Photo credit: tanjila ahmed/Flickr (CC BY 2.0)

Through a mouse model.

According to a new study by researchers from the McGill University Health Centre in Montreal, a type of brain cell, microglia, plays a key role in decreasing the effects of cocaine in the brain.

Microglia are responsible for a number of important functions in the brain — they monitor their environment and act appropriately to maintain normal brain functioning, and they can also produce molecules that cue neurons to make adaptive changes to their connections. An example of this is an inflammatory molecule called tumor necrosis factor (TNF).

The research, which appears in the journal Neuron, is the first study to establish that microglia could have significant implications for developing effective cocaine addiction treatments by lowering the adverse changes to neural circuitry brought on by chronic use of the drug.

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"What we discovered is that cocaine activates these microglia, which causes the release of an inflammatory signal which then tries to reverse the changes that cocaine is inducing in the neurons," senior author David Stellwagen, a researcher from the Brain Repair and Integrative Neuroscience and associate professor in the Department of Neurology and Neurosurgery at McGill University, said in a press release.

The scientists used a mouse model to detect how TNF acts on a particular set of synapses in the brain.

"These connections are really important for regulating the behavior response in animal models to drugs of abuse such as cocaine," said co-first author Sarah Konefal, a McGill doctoral student.

According to the report, the team found that TNF suppresses specific cocaine-induced synapse changes — and these changes are thought to underlie addiction.

However, Stellwagen explains that this beneficial microglial response fades over time.

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“One of the things that could transition somebody from just casual use into chronic dependency might be the fading of this adaptive signal which then allows the drugs to solidify their change to the neural circuitry,” he said.

In order to find out if the microglia could be enticed to keep going, the scientists used a pharmaceutical agent that stimulates the production of TNF. They observed that a cocaine-induced behavioral change was reduced in the mice who received the agent.

According to the release, cocaine relapse rates can “run as high as 80 per cent,” so these results hold promise for developing future treatments that could cut down the relapse rates.

"If we could develop a treatment that would suppress the craving that addicts have in stressful situations, or when they are re-exposed to situations in which they'd normally be taking the drug, that may allow them to avoid relapse,” says Stellwagen. “And that's really the therapeutic goal of the work we have been doing."

Next, the researchers are investigating whether the stimulated release of TNF could actually suppress cocaine cravings, as well as whether this work could be translated to other addictive substances, like alcohol and methamphetamine.

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