For recovering alcoholics, memories associated with drinking — the smell of a bar, ice clinking in a glass — are among the greatest threats to sobriety.
But what if retrieval of those memories could be blocked? Using a drug typically given to organ-transplant patients, researchers at the University of California, San Francisco, reduced the incidence of relapse in rats by disrupting memories linked to past drinking.
For several weeks the researchers allowed rats to binge on alcohol. Then, after 10 days of abstinence, the rats were exposed to just a drop of alcohol — enough to awaken their memories of drinking. The researchers then used brain scans to identify the neural mechanism responsible for triggering the reactivation of those memories, known as the mTORC1 signaling pathway.
Rapamycin, a drug known to disrupt the pathway, was then given to some of the rats. Those that received it were significantly less likely to consume alcohol.
“A single administration of this drug prevented relapse for a period of two weeks,” said Dorit Ron, a neuroscientist at the university and an author of the study, which was published in the journal Nature Neuroscience. Just how long the rats might have stayed dry is hard to say, she added, because “two weeks is when we ended the study.”
Rapamycin, which is normally used to suppress transplant patients’ immune systems, is already approved by the Food and Drug Administration. But more study is required to determine whether it could help people abstain from alcohol, Dr. Ron said, adding that the drug also has significant side effects, including increased susceptibility to infection.
This article has been uploaded to the DF archive:
Segev Barak, Feng Liu, Sami Ben Hamida, Quinn V Yowell, Jeremie Neasta, Viktor Kharazia,
Patricia H Janak, & Dorit Ron. Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse. (2013) Nature Neuroscience, doi:10.1038/nn.3439, Published online 23 June 2013
Relapse to alcohol abuse is an important clinical issue that is frequently caused by cue-induced drug craving. Therefore, disruption of the memory for the cue-alcohol association is expected to prevent relapse. It is increasingly accepted that memories become labile and erasable soon after their reactivation through retrieval during a memory reconsolidation process that depends on protein synthesis. Here we show that reconsolidation of alcohol-related memories triggered by the sensory properties of alcohol itself (odor and taste) activates mammalian target of rapamycin complex 1 (mTORC1) in select amygdalar and cortical regions in rats, resulting in increased levels of several synaptic proteins. Furthermore, systemic or central amygdalar inhibition of mTORC1 during reconsolidation disrupts alcohol-associated memories, leading to a long-lasting suppression of relapse. Our findings provide evidence that the mTORC1 pathway and its downstream substrates are crucial in alcohol-related memory reconsolidation and highlight this pathway as a therapeutic target to prevent relapse.
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