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"Eternal Sunshine" Drug Makes a Rat Forget Bad Things [Video]

Watch how a druglike compound with the eponymous name of ZIP appears to completely wipe out long-term memory in a rat
rat, Jerry Adler, Eternal Sunshine Drug, PTSD


Working at Scientific American, known for its spiffy technical illustrations, I always look for material that can show what an article is trying to tell. I’ve never found a better example than this video(below) of a rat fed a drug that wipes out its long-term memory, and which bears a real-life resemblance to the scenario depicted in Eternal Sunshine of the Spotless Mind. The opening paragraphs of the article by Jerry Adler, called “Erasing Painful Memories.”  serves as a running narrative to the video. I’ve included them here:

 

The rat is on a carousel with clear plastic sides, rotating slowly in a small room. As it looks out through the plastic, it sees markings on the walls of the room from which it can determine its position. At a certain location it receives a foot shock—or, in experimenters’ jargon, a negative reinforcement. When that happens, the rat turns sharply around and walks tirelessly in the opposite direction, so it never reaches that same place in the room again. It will do this to the point of exhaustion.

Question: How do you get the rat to stop walking?

Note that just turning off the shock will not suffice, because the rat will not allow itself to enter the danger zone. The rat needs an intervention that helps it forget its fear or that overrides its response with a competing signal of safety. So much for the rat. Now think of someone who has been wounded in combat and suffers from the vague but real cluster of symptoms called post-traumatic stress disorder (PTSD). He, too, associates specific contexts or stimuli—open spaces, crowds, sudden loud noises—with something painful.

He avoids those circumstances when he can. He is in the same bind as the rat on the turntable: unable to discover for himself that certain situations are now safe. How do we get him to stop running? The rat on the carousel and the veteran on a crowded street are both prisoners of the extraordinary power of pain to forge an indelible impression on the brain: be it mammalian, reptile or even invertebrate.

The rat on the carousel and the veteran on a crowded street are both prisoners of memory, of the extraordinary power of pain to forge an indelible impression on the brain: be it mammalian, reptile or even invertebrate. As some researchers labor to solve the mystery of memory loss in dementia, others are attacking the mirror image problem of how to help patients escape the painful memories that dominate their daily life—and not just those with  PTSD. An emerging new paradigm views such diverse conditions as phobias, obsessive- compulsive disorder, and even addiction and intractable pain as disorders of learning and memory or, more pointedly, forgetting.

Some people never forget the time a spider fell into their glass of milk. Others cannot break the association of certain places or situations with getting high. Now researchers are finding that remembering is not just a process of passively storing impressions. It is a continuous, dynamic activity on the cellular level and an ongoing psychological process open to  manipulation with drugs and cognitive therapy. This is wonderful news for combat veterans and victims of assaults and accidents. What it means for future generations of historians and personal-injury lawyers remains to be seen.

For the rat on the carousel, you can imagine different approaches to extinguishing its fear. You could let it walk to exhaustion and learn for itself that the shock has been turned off—a process psychologists call extinction. Or you could try tinkering directly with the rat’s brain—specifically, the hippocampus, where place memories are formed and stored. Six years ago neuroscientist Todd Sacktor of S.U.N.Y. Downstate Medical Center in Brooklyn, building on work with his former colleague Andre Fenton, did just that. He injected a compound called ZIP into the hippocampus of a rat that had been trained onthe carousel and, after two hours, tested it again and found the fear had been erased. Do that in a combat veteran disabled by PTSD, and you are on the way to a Nobel Prize or a billion-dollar drug bonanza.

The article then goes on to explain other approaches that researchers are undertaking to help people forget or dull bad memories. Adler’s introduction serves as a general description of the video. The specific component segments are:

  1. Pretraining: The rat, in this video playing at five times normal speed, gets used to life on the carousel. Note the unactivated, pie-shaped area used to deliver a shock.
  1. Training Trial 8 (shock on): Now the shock is turned on, and the rat steers well clear of the demarcated red slice.
  1. One-day retention: saline-injected rat (shock off): A day later, a rat injected with harmless saline remembers the aversive shock, steering clear of the triangular zone.
  1. One-day retention: ZIP-injected rat (shock off): The rat that has ZIP injected into its brain wanders freely the breadth of the carousel without any memory of having been shocked.
  1. Pretraining vs. One-day retention: (Zip- Injected): A side-by-side comparison shows that the Zip-injected rat behaves exactly as it did before it received the first shock.


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