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Israeli scientists find connection between memory, association, and drug addiction

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According to scientists at Hebrew University, “our brains are wired to retain information relating to highly significant events. This mechanism also underlies drug addiction and is the reason why hanging out in an environment or with people associated with memories of drug use often leads to relapse.”

By ILANIT CHERNICK

The way in which our brains create strong associations with certain significant events in our lives is somewhat of a mystery.

However, researchers at the Hebrew University (HU) have found that a relatively obscure brain region known as the claustrum plays a significant role in making these connections.

The team, led by Prof Ami Citri and PhD student Anna Terem of HU’s Edmond and Lily Safra Center for Brain Sciences and the Alexander Silberman Institute of Life Science, explained that “our brains are wired to retain information that relates to the context in which highly significant events occurred.  

“This mechanism also underlies drug addiction and is the reason why hanging out in an environment or with people associated with memories of drug use often leads to relapse,” the duo said. 

According to the team, their findings fit the idea of “incentive salience.” This is a process that “determines the desirability of an otherwise neutral stimulus.”

Highlighting how this works, the team said the perfect example is how a candy store façade becomes attractive to children after they’ve had repeated exposure and associations with the delicious treats that lie within.  

“With time, children unconsciously learn to ‘want’ to see the store stimulus, which is separate from their ‘liking’ the actual candy reward,” the duo pointed out. 

To examine how context becomes associated with addiction, in this case cocaine, the researchers discovered a group of neurons within the claustrum region that lit up during cocaine use.  

“These neurons,” they said, “are pivotal in the formation of an incentive salience that links context with the pleasure of cocaine.”

To determine how and when the claustrum plays a role in incentive salience, Citri and his team employed a conditioned-place preference (CPP) test for a group of lab mice. 

Using mice to determine when and how the claustrum participates incentive salience, the team found that mice learned to associate the reward with context. 

The researcher then administered cocaine to the mice and placed them in an area with distinctive flooring, which was rugged, and had wall patterns with dots – insignias that a mouse would notice once the drug started to kick in.  

Featured Image: Hebrew University Researcher Anna Terem working in the lab.
Above Image: Hebrew University Prof. Ami Citri
(Credit: Courtesy of Hebrew University)
 

After doing this several times, Ciri explained that when the mice were placed in a room where they could choose to either hang out in a region similar to the one paired with the cocaine that includes rugged floors and dotted walls, or a neutral area with smooth floor and striped walls, “the mice would quickly congregate in the area where their drug high had played out.

“These findings boosted our confidence that the claustrum is indeed integral to incentive salience, heightening the awareness of the mouse to the context in which it experienced the drug high” Citri highlighted.

When it came to testing how the claustrum is involved in context being associated with a given reward, Citri and his team observed the changes in mice behavior when they inhibited these claustral neurons. They found that the suppression of these neurons inhibited the mice’s behavioral responses to cocaine, which means that they no longer preferred hanging out in the cocaine-paired environment. 

“On the other hand, activating these neurons – even in the absence of any cocaine – caused the mice to develop a preference for this context,” the team reported.

The team also made an important discovery. They found that the activity of the claustrum was not necessary for retrieval of the cocaine memory. 

Citri pointed out that after “the mice had been placed in a cocaine-paired context several times to enjoy their cocaine high, the memory for this context was encoded and inhibition of the claustrum had no effect on their preference for the cocaine-paired context.

“These findings boosted our confidence that the claustrum is indeed integral to incentive salience, heightening the awareness of the mouse to the context in which it experienced the drug high” Citri emphasized.

Addressing the implications of the study, Terem explained that as the number of deaths caused by drug overdose increases from year to year, “this new study gives… a better understanding of the nature of addiction and the importance of breaking contextual cues before they develop. 

“By recognizing that the claustrum plays a pivotal role in creating a context association for reward, it becomes a structure of interest for the field of addiction,” she said. 

Terem concluded that they “hope this knowledge will lead to the development of new diagnostic tools to identify populations susceptible to addiction, as well as new therapeutic approaches.” 

 They published their findings in the latest edition of Current Biology.

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