Addiction May Be Thwarted By Deactivating Memories

Research at the Ernest Gallo Clinic and Research Center at UC San Francisco may eventually lead to revolutionary treatment options for people who suffer from alcohol abuse disorder and drug addiction.

By identifying and deactivating certain neural pathways – those linked to memories – scientists found it quelled the addictive cravings for alcohol in lab-rats. Researchers were able to prevent the urge to seek alcohol and drink it – the equivalent of relapse.

Statistically, over 70 percent of human addicts relapse within the first few years of detox rehabilitation and treatment – succumbing to triggers. Therefore, scientists have been laboring to find ways of snuffing out powerfully influential addiction mechanisms in the brain.

According to the research fellow, Segev Barak, PhD, in Science Daily:

“One of the main causes of relapse is craving, triggered by the memory by certain cues – like going into a bar, or the smell or taste of alcohol. We learned 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 even erase the memory, and thus the craving.”

Initially, rats were introduced to alcohol over the course of seven weeks. During the next phase, they had the opportunity to access alcohol for one hour a day. The test animals were then put through a 10-day period of detox.

Following the abstinence, the rodents were exposed to the smell and taste of alcohol for five minutes, which cued them to remember how much they liked drinking it. While doing so, researchers scanned their tiny brains and identified the neural mechanism responsible for the reactivation of the memory of alcohol.

This molecular pathway is mediated by an enzyme known as mammalian target of rapamycin complex 1 (mTORC1). The standard role of mTORC1 is to activate translation of proteins.

A single drop of alcohol presented to the rats turned on the mTORC1 pathway – specifically in a select region of the amygdala, a structure linked to emotional reactions and withdrawal from alcohol, and cortical regions involved in memory processing.

Once activated, the alcohol-memory correlated with an increased relapse.

Using a drug call rapamycin, researchers managed to deter reversion by deactivating mTORC1. Previous studies have shown rapamycin has been widely used as a partial inhibitor of the mTORC1 nutrient-sensitive signaling complex.

A dose was administered immediately after the exposure to the smell and taste cues. The urge to drink alcohol was suppressed for 14 days – up to the end point of the study – suggesting rapamycin may erase the psychosomatic memory response to crave and therefore seek alcohol.

Rapamycin, also known as sirolimus, is an immunosuppressant drug used to prevent rejection in organ transplantation. It has been especially useful in kidney transplants. It prevents activation of T cells and B cells by inhibiting their response to interleukin-2 (IL-2).

Rapamycin was originally developed as an antifungal agent. However, this use was abandoned when it was discovered to have potent immunosuppressive and anti-proliferative properties.

The study, also supervised by co-senior authors Patricia H. Janak, PhD – a Gallo Center investigator and UCSF professor of neurology – and Dorit Ron, PhD, was published in Nature Neuroscience.

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