Blocking Memories Of Meth
(Inside Science) -- Relapse is a fear that plagues almost every person fighting drug addiction -- it's often a memory of the hit that's to blame. The relapse rate is high in the case of methamphetamine; it's one of the hardest drugs to kick.
Studies have estimated that only 12 percent of meth users will make a long-term recovery.
But what if you could chemically alter the brain with a drug to block the memory of feeling a high? In effect, what if you could erase the memory?
That's what researchers at The Scripps Research Institute, in Jupiter, Florida, say they've done with meth-addicted mice in a new study published recently in the journal Molecular Psychiatry.
"I think the paper is important and it's an area that I'm sure will be more thoroughly explored by this group and hopefully others," wrote Barbara Sorg, a professor in the neuroscience department at Washington State University, in Vancouver, in an email.
Sorg's own research focuses on how to reduce relapse in cocaine-addicted mice. She was not involved in the new study.
The Scripps researchers administered a dose of methamphetamine to a group of 29 mice over the course of six to eight days. The mice were then enclosed, one at a time, in a box for 30 minutes. The same day, the mice were also given saline before placing them in a different colored box.
"They learn to associate either meth or saline with the different colored boxes at the end of training," said study author Erica Young.
Forty-eight hours later Young and her colleagues administered 14 of the mice with a placebo control and the other 15 with a drug called Blebbistatin -- or Blebb for short. Then 24 hours later they let the mice choose between the two boxes.
"The control animals go and hang out and wait for the meth. They're spending the majority of their time in the meth box," said Young. The Blebb animals on the other hand did not show any preference.
The reason why Blebb affects behavior, the researchers think, comes down to how the medication influences memory. When memories are created, a protein called actin attaches and reattaches itself to nerve cells in the brain. That process usually stabilizes after about ten minutes for most normal recollections like food or fear-related memories, said Young.
But when the memory of taking an addictive drug and of feeling its hit is stored, the actin remains active. "With drug-related memories, once the memory forms it never stops," explained Young.
Blebb works by targeting something called a molecular myosin motor. The motor's function is to chop large actin molecules into smaller ones, making the actin more numerous in the nerve cells.
"Blebb stops it from chewing up the actin," explained Young. Essentially the drug prevents the actin from multiplying and allows the storage of the meth memory to stabilize like a typical memory.
Young and her fellow researchers ran multiple similar and repeat behavioral experiments for this study and all of them confirmed this finding. The total number of mice came in at 47 for the control and 43 for the Blebb.
Sorg wrote she was impressed that Blebb was able to have this effect 24 hours after it was administered, rather than at the time of choice. That's an indication that the medication could prevent relapses.
The effect also persisted for 30 days, but Young thinks it could permanently prevent relapse caused by meth-associated memories.
"It's one of the many happy surprises of this project," said Young, "We fully expect that they wouldn't relapse a year or more later, but we don't know for sure yet."
Young maintained Blebb only targets the meth-associated memory. "Meth memories are vulnerable to destruction in this way, but our normal memories are pretty ironclad," she said.
But Sorg is less certain. "It is hard to know whether they diminished the expression of other memories," she wrote.
The memory making capacity of the mice wasn't damaged, said Young, which she confirmed by making them learn a new fear-related memory after the experiments. That suggests they haven't stopped acquiring memories, according to Young.
But, for now it's unknown whether other non-meth memories formed before the experiment remained intact. This is one of the questions the researchers want to research in the future.
The next stage of Young and her colleagues' research is to look into the potential of Blebb to prevent relapse for other addictive drugs such as cocaine and heroin.
Sorg and Young agree that Blebb needs to be tested for potential side effects before it can help humans suffering from addiction.
Nevertheless, Sorg remains excited by the research. She wrote, "Meth addiction is an intractable problem with no treatments, and I'm happy to see more researchers turning their attention to it."