Alcoholics -- so far at least rats addicted to the bitter drop -- can be saved from relapse following abstinence from drinking by turning off a trigger in the brain. Israeli and US researchers were able to identify and deactivate a brain pathway linked to cravings for alcohol, thus preventing the rodents from seeking alcohol and drinking it.

The researchers -- headed by Dr. Segev Barak of Tel Aviv University’s School of Psychological Sciences and the Sagol School of Neuroscience, Profs. Dorit Ron and Patrician Janak of the University of California at San Francisco, on Sunday night published their findings online in Nature Neuroscience. The study was conducted in the University of California, San Francisco, in the lab of Professor Dorit Ron.

Although the research was conducted in lab animals, the authors believe it is quite possible that similar studies will soon test the same treatment strategy in humans, and that the study paves the way for treatment of other addictions, including tobacco.

“One of the main causes of relapse is craving, triggered in the memory by certain cues -- like going into a bar, or the smell or taste of alcohol,” said Barak, the lead author. “What we learned is that when rats were exposed to the smell or taste of alcohol there was a small window of opportunity to target the area of the brain that reconsolidates the memory of the craving for alcohol and to weaken or erase the memory -- and thus the craving.”

In the study, researchers trained rats to voluntarily access 20 percent alcohol solution in special chambers by pushing levers, and they drank high amount of alcohol for three months. They were then put through a 10-day period of abstinence from alcohol.

Later the animals were exposed to alcohol either by smell or taste. In the first part of the experiment, rodents were then killed (under anesthesia) and their brains scanned to identify the neural pathway that retrieved and reconsolidated -- the memory of the alcohol. They found activation of a molecular pathway called the mammalian target of rapamycin complex 1 (or, mTORC1). This activation was specific to a select region of the amygdala, a structure linked to emotional reactions and withdrawal from alcohol, and cortical regions involved in memory processing.

In the second part. the researchers sought to prevent the reconsolidation of the memory, thus preventing relapse. They found that when the rats were presented with just a small drop of alcohol, the smell and taste activated the mTORC1 pathway. Once mTORC1 was activated, the alcohol-memory stabilized (reconsolidated) and the rats relapsed on the following days, meaning in this case, that they pushed the lever to dispense more alcohol.

However, in rats where the mTORC1 pathway was deactivated using a drug called rapamycin, administered immediately after the exposure to the cue (smell, taste), there was no relapse to alcohol seeking the next day, and drinking remained suppressed for up to 14 days, the end point of the study.

“The smell and taste of alcohol were such strong cues that we could target the memory specifically without impacting other memories (like a craving for sugar, for example),” said Barak, who added that he has been doing brain studies for many years and has never seen such a robust and specific activation in the brain.

The study is an “important first step in the research, but more studies are needed to determine whether rapamycin -- a drug currently approved as an immunosuppressant for kidney transplant patients -- would have the same effect in humans.  In future research, Barak plans to investigate in his TAU lab whether the use of behavioral manipulations, in lieu of pharmaceuticals, could produce similar results.

“One of the main problems in alcoholism is relapse, and there are not many treatments. Even with an efficient treatment, 70% to 80% of the patients will relapse in the first year,” Barak says. “It’s really thrilling that we were able to completely erase the memory and prevent relapse in these animals. This could be a revolution in treatment approaches for addiction, in terms of erasing unwanted memories and thereby manipulating the brain triggers that are so problematic for people with addictions” he said.

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