Drug addiction is racing in my brain. You want me to stop it by willpower? Installing a brake may help.

Author: Project Lailai Team (Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences and Duchuang Technology)

The article comes from the Science Academy official account (ID: kexuedayuan)

Is drug abuse really just about pursuing a sense of pleasure? Can drug rehabilitation be successful with strong willpower?

Thinking too much...Drugs can change the neural circuits in the brain. Under the strong corrosion, the urge to take drugs cannot be stopped at all!

Now, Stanford researchers suggest they have found a way to artificially put a "brake" in the brains of drug addicts.

Drug abuse makes the "courier brother" lose his job

The human brain contains hundreds of billions of nerve cells. Our ability to eat and sleep, and our ability to feel the fear of being dominated by deadlines, are all the result of information being transmitted in the brain's nerve cells.

Dopamine is the neurotransmitter responsible for transmitting happy information: the sun is shining, the wind is warm... After the senses receive this information, the "delivery boy" dopamine is responsible for transmitting it to the brain, and we will feel happy.

Of course, the brain is not so easy to please.

Suppose there is a counter in the brain. Every time dopamine transmits a message of happiness, the counter silently increases by 1. Only when the counter exceeds a certain value will the brain feel happy. This value is called the threshold.

After taking drugs, drugs can produce thousands of happy messages at once, without bothering dopamine at all. The value of the brain counter rises rapidly, the threshold standard is raised, and at the same time, the secretion of "unemployed" dopamine becomes less and less. The direct consequence is that people can no longer feel happy.

What to do? You can only rely on drugs to feel happy again. But the more you take drugs, the higher the threshold becomes, and the less dopamine you have, so you can only take more... This is addiction.

This is beyond my control.

If you are addicted to drugs, you will die miserably and live a life worse than death. Quit drugs! I believe that your strong willpower will definitely defeat drugs!

However, quitting drugs is not a matter of willpower alone.

If you suddenly stop taking some drugs after taking them for a long time, you will have a strong withdrawal reaction, manifested as nausea, vomiting, depression, anxiety... Once the drug addiction comes, it is impossible to stop.

In short, the more enjoyable you are when taking drugs, the more depressed you will be after you stop taking them. Many people fail to quit drugs repeatedly, not because they can't let go of the high feeling when taking drugs, but because they can't overcome the emptiness after stopping taking drugs.

What’s worse is that due to the environmental memory of the brain, during the period of drug rehabilitation, watching the dramas you watched when you were taking drugs, or drinking the beverages you drank when you were taking drugs, the memories will push you towards drugs like a tide.

Among the addictive drugs that can cause withdrawal symptoms, opioids are the most popular and the most harmful.

Morphine and heroin are both opioids

How the withdrawal reaction occurs and which brain area controls it was not clear until the emergence of the "Stanford researcher" mentioned above.

On a normal working day, Zhu Yingjie, a postdoctoral student at Stanford, came to the laboratory early in the morning as usual to conduct the Nth experiment on mice: giving them opioids, then stopping the drugs and observing their withdrawal reactions.

That day, he discovered that in mice showing withdrawal symptoms, a neural pathway seemed to be activated in the brains of mice. This pathway is called the glutamatergic neural pathway from the paraventricular nucleus of the thalamus (PVT) to the nucleus accumbens (NAc).

The rabies virus (red fluorescent area in the picture) was injected into the NAc in the mouse brain, and labeled red cells were found in the PVT, thus proving the existence of the neural pathway from PVT to NAc (Picture from the Institute of Brain Cognition and Brain Diseases, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences)

With excitement, Zhu Yingjie conducted a careful academic search and found that no one had published a paper on the relationship between withdrawal reaction and this neural pathway.

But does this neural pathway belong to the brain area that determines withdrawal symptoms?

After a brief dopamine transmission, Zhu Yingjie embarked on a longer experimental journey and chose optogenetics.

An exogenous gene is injected into the brain of a mouse. The protein encoded by this gene enables nerve cells to respond sensitively to stimulation from light of different colors. Then an optical fiber is implanted in the brain to control the activity of nerve cells with light.

Optical fiber implanted in mouse brain

In layman's terms, Zhu Yingjie implanted a light-controlled "brake" in the brain of a mouse, and then inhibited the activation of the pathway from the paraventricular nucleus of the thalamus to the nucleus accumbens through external light control.

Black represents mice without "brakes" installed, and green represents mice with them installed. On the left are three behavioral indicators of withdrawal symptoms (jumping, rearing, tremor), and on the right are memories of withdrawal symptoms. It can be seen that optogenetic inhibition of this pathway can eliminate withdrawal symptoms (Image from the Institute of Brain Cognition and Brain Diseases, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences)

In addition, the synaptic strength on the neural pathways of mice with withdrawal reactions was significantly enhanced. Synapses are the key site for information transmission between neurons. Through optogenetics, the increase in synaptic strength can be artificially reversed, thus inhibiting the withdrawal reaction.

Two and a half years had passed since the discovery was made in 2014 and the paper was published in 2016. In the science and technology world where updates are made every day, two and a half years can be considered a long time. The paper was finally published in the top international journal Nature, which immediately attracted widespread attention. The industry has high hopes for this milestone discovery.

From treating mice to treating humans

After returning to China, Zhu Yingjie joined the Institute of Brain Cognition and Brain Diseases at the Shenzhen Institutes of Advanced Technology of the Chinese Academy of Sciences. The next step is to make this discovery truly help people quit drug addiction.

Since optogenetics requires craniotomy and surgery, it is currently only used on animals. After clarifying the brain area where the withdrawal reaction of opioids is affected, Zhu Yingjie hopes to find other non-invasive methods, such as ultrasound, magnetic field, and electric field stimulation, to achieve the purpose of drug detoxification. The Institute of Advanced Technology has many projects related to ultrasound and magnetic fields. If we can combine Zhu Yingjie's findings, perhaps we can look forward to the emergence of electromagnetic drug detoxification caps and ultrasonic drug detoxification devices in the future.

Note: Zhu Yingjie published a paper in Nature titled: A thalamic input to the nucleus accumbens mediates opiate dependence (A neural pathway from the thalamus to the nucleus accumbens mediates opiate dependence).

This article is produced by the Project is Coming team. Project is Coming is a technology column created by the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences and DuChuang Technology, which provides a new interpretation of relevant projects in strategic emerging industries.