Addiction relapse might be thwarted by turning off brain trigger

A new study by researchers at the Ernest Gallo Clinic and Research Center at UC San Francisco offers encouraging findings that researchers hope may one day lead to a treatment option for people who suffer from alcohol abuse disorders and other addictions.

In the study, conducted in rats, the UCSF researchers were able to identify and deactivate a brain pathway linked to the memories that cause cravings for alcohol, thus preventing the animals from seeking alcohol and drinking it, the equivalent of relapse.

"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," said lead author Segev Barak, PhD, at the time a postdoctoral fellow in the lab of co-senior author Dorit Ron, PhD, a Gallo Center investigator and UCSF professor of neurology.

"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" he said.

The study, also supervised by co-senior author Patricia H. Janak, a Gallo Center investigator and UCSF professor of neurology, will be published online on June 23, 2013 in Nature Neuroscience.

In the first phase of the study, rats had the choice to freely drink water or alcohol over the course of seven weeks, and during this time developed a high preference for alcohol. In the next phase, they had the opportunity to access alcohol for one hour a day, which they learned to do by pressing a lever. They were then put through a 10-day period of abstinence from alcohol.

Following this period, the animals were exposed for 5 minutes to just the smell and taste of alcohol, which cued them to remember how much they liked drinking it. The researchers then scanned the animals' brains, and identified the neural mechanism responsible for the reactivation of the memory of the alcohol - a molecular pathway mediated by an enzyme known as mammalian target of rapamycin complex 1 (mTORC1).

They found that just a small 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.

They further showed that once mTORC1 was activated, the alcohol-memory stabilized (reconsolidated) and the rats relapsed on the following days, meaning in this case, that they started again to push the lever to dispense more alcohol.

"The smell and taste of alcohol were such strong cues that we could target the memory specifically without impacting other memories, such as a craving for sugar," said Barak, who added that the Ron research group has been doing brain studies for many years and has never seen such a robust and specific activation in the brain.