When Ivan Pavlov's dog heard the ding of a bell, the pup started salivating in anticipation of his dinner. When professor Mary Torregrossa's rats heard a similar tone, they craved cocaine. At least, some of them did — before Torregrossa and her colleagues rewrote their memories.
Torregrossa studies the psychology of drug addiction and relapses at the University of Pittsburgh School of Medicine (where she is also an associate professor of psychiatry). In a new study published Jan. 22 in the journal Cell Reports, Torregrossa and two of her colleagues set up a Pavlovian experiment in which a group of lab rats came to associate a specific audiovisual cue with the rush of a cocaine infusion.
Eventually, merely seeing or hearing the cue made the rats crave more cocaine — until the researchers "erased" that association from the rats' brains using a neural-stimulation technique called optogenetics. Suddenly, rats exposed to the same audiovisual cue that once made their brains glow with anticipation showed no interest in the cue at all. [Top 10 Mysteries of The Mind]
"It was like they had never seen cocaine," Torregrossa told Live Science. "That's exciting, because there's the possibility that, down the road, there could be neural-stimulation technologies that could possibly reduce cue-motivated craving and relapse in humans, too."
Eternal sunshine of the rodent mind
In the new study, Torregrossa's rats were placed one by one into a special cage with a lever connected to a pump. When a rat pressed the lever, the pump gave that rat a small, intravenous dose of cocaine. Each time this happened, a bright light above the lever lit up for 10 seconds while a monotonous ringing noise played in the cage.
After a rat repeated this ritual many times, Torregrossa said, the combination of light and noise became a "cue" that the rush of a cocaine high was on its way — sort of like Pavlov's famous doggy dinner bell, but set for self-medicating rodents.
Whenever the rats were exposed to this light/sound cue in subsequent trials, their brains showed what Torregrossa called a "craving" or "relapse response" to the stimuli, and the rats continued to mash the lever "at really high rates," even when the lever was no longer providing them with cocaine.
Using tiny electrodes placed in each rodent's brain, the researchers saw that this craving response was associated with heightened activity in a rat's amygdala — an emotional processing center responsible for both fear and pleasure. (This almond-shaped cluster of neurons has previously been linked to craving in humans, too.)
"Next, we wanted to see if we could artificially reduce those cravings by stimulating the pathway into the amygdala," Torregrossa said.
To do this, the researchers used a technique called optogenetics — a way of introducing light-sensitive proteins into an animal's brain, then exposing them to colored beams of light to effectively switch cells "on" or "off" at will. [3D Images: Exploring The Human Brain]
In previous studies, scientists have successfully used this technique to stop mice from having epileptic seizures, or make them thirsty on command. Torregrossa and her team wanted to use it to turn off their rats' cue-induced cravings. So, they injected their rats with a special virus carrying light-sensitive proteins, which set up shop at the cellular junction where sensory information (such as sound and light) enters the amygdala.
By bathing those cells in a blue LED laser light, the researchers could control the flow of information into the rats' emotion-processing hubs. In this case, that meant dampening the significance of the drug cue as it entered the amygdala. Indeed, when they combined this blue light stimulation with the rats' familiar Pavlovian drug cues, the researchers found they could essentially trick the rodents into forgetting that the sound/light combination had anything to do with the pleasure of a cocaine high. Suddenly, they had far less interest in hitting the cocaine lever in their cages.
"After just 15 minutes of this blue light stimulation, the rats' relapse behavior was markedly reduced," Torregrossa said. "It's essentially like we erased their memories, so they didn't respond to that cue anymore."
"Very futuristic" questions
While this apparent memory-erasure technique is a fascinating find, Torregrossa noted that it could be a temporary fix to a much more complicated puzzle of how addiction alters the brain. It's possible, for example, that if the newly rehabilitated rats were once again given cocaine in the presence of that familiar audiovisual cue, their craving and relapse impulses would "be back in one shot," the way they were before.
Still, the team's success raises some interesting possibilities for the future of monitoring and treating addiction, and possibly even brain disorders, in humans. Torregrossa said she has started talking to her colleagues at the University of Pittsburgh's neural engineering department about the viability of neural implants that could monitor a person's amygdala neurons, then be activated to suppress a craving or relapse response.
This is all "very futuristic," however, Torregrossa said, and — if such a treatment is possible in humans — it's also mired in ethical questions. If the flick of a switch can "erase" the memory of a drug-relapse trigger, what else could it erase? Could good memories get caught in the crossfire? Could entire people, places or experiences be erased in full-blown "Eternal Sunshine of The Spotless Mind" fashion?
"How can we only affect the bad memories that we don't want to cause relapse — and leave everything else alone?" Torregrossa asked. "How far down that road do we go in affecting a person's thoughts?"
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Originally published on Live Science.
