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CLEVELAND, Ohio-- There are occasional innovations that revolutionize a scientific field, offering answers to questions that had once been only theoretical.
Mapping the human genome was one such advance.
Optogenetics is another. The technique, which over the past eight years has galvanized brain research, has transformed neuroscientists from passive observers of the brain to active manipulators of its workings.
Amazingly, these researchers can now use hair-thin fiber-optic laser lights to turn individual brain cells on or off, and can watch as their animal subjects' behavior changes accordingly.
The most recent study to make use of the method in rats has immediate implications for the approximately 1.4 million Americans who are addicted to cocaine.
Researchers with the National Institutes of Health, the Ernest Gallo Clinic and the Research Center at the University of California, San Francisco, successfully used optogenetics to cure cocaine addiction in rats by stimulating the prefrontal cortex, a part of the brain that had been "silenced" by repeated exposure to the drug.
The health consequences of cocaine addiction are serious. Heavy use may double the brain's aging. Even occasional use of cocaine may boost the risk of heart problems, and the drug is also a leading cause of heart attacks and strokes for people under 35.
"We don't need to wait 10 or 15 years to possibly figure out what to give to patients as a therapy -- we have the ability now to set up clinical trials and hopefully try to help patients within a matter of months."
Bonci and his team think they could have a TMS clinical trial for cocaine addicts recruiting patients by the end of the year.
Their confidence stems from the somewhat stunning black-and-white nature of their results in rats, which were unheard of before optogenetics. Their study, published in April in the journal Nature, explained how rats trained to seek cocaine rewards were cured by a switch in the prefrontal cortex.
To produce a group of rats that closely mimic human addiction, the researchers first gave the animals free access to cocaine, which they could get by pressing a lever. Then they introduced mild shocks to the rats' feet at random intervals as a negative consequence of the drug use.
About 70 percent of the rats stopped pressing the lever when the shocks started. The rest, though, kept compulsively seeking the cocaine reward despite the unpleasant result; they were addicted.
"The addicted rats showed this silence in that part of the brain," Bonci said, which the researchers were able to measure electrically after the animals were euthanized. The prefrontal cortex, the area "silenced" by the cocaine addiction, correlates to the dorsal anterior cingulate cortex in people, he said.
"Human studies have shown that chronic cocaine abusers do have a very low productivity in that area," Bonci said. Both brain areas appear to be implicated in regulating the conscious control of decisions that either harm or benefit: In this case, should I take the drug, or not?
The addicted rats' brain cells in this area were then turned into on/off switches using the optogenetics technique. Researchers injected special light-activated proteins (called rhodopsins) targeted to that brain area by genetic manipulation, and implanted the tiny fiber optic cables.
With the flip of a switch, laser light from the fiber-optic cable turned on activity in the prefrontal cortex, and "within a matter of hours" the addicted rats were no longer addicted.
Even more amazing, perhaps, is what the group did to further prove that they were targeting the right area. They took the nonaddicted rats (the ones that stopped going after the cocaine when shocked) and used their method to turn off the prefrontal cortex area. The rats became addicts just as quickly.
"This is amazing," Bonci said. "It shows causality, that the activity of this brain region is clearly tied to this behavior, but also that the brain can go back to normal after months of exposure to something that is pretty toxic."
"[TMS] is cruder, but of course the advantage is that it's not invasive and you have nearly zero side effects," he said. "What matters for now is that we know what we should be doing in that brain region to try to reduce craving. We know what to do and we have proof that it should work."
And that's very good news for the millions of people struggling with addiction and for those who love them, too.
Mapping the human genome was one such advance.
Optogenetics is another. The technique, which over the past eight years has galvanized brain research, has transformed neuroscientists from passive observers of the brain to active manipulators of its workings.
Amazingly, these researchers can now use hair-thin fiber-optic laser lights to turn individual brain cells on or off, and can watch as their animal subjects' behavior changes accordingly.
The most recent study to make use of the method in rats has immediate implications for the approximately 1.4 million Americans who are addicted to cocaine.
Researchers with the National Institutes of Health, the Ernest Gallo Clinic and the Research Center at the University of California, San Francisco, successfully used optogenetics to cure cocaine addiction in rats by stimulating the prefrontal cortex, a part of the brain that had been "silenced" by repeated exposure to the drug.
The health consequences of cocaine addiction are serious. Heavy use may double the brain's aging. Even occasional use of cocaine may boost the risk of heart problems, and the drug is also a leading cause of heart attacks and strokes for people under 35.
While researchers won't be implanting fiber optics into human brains anytime soon to short-circuit addiction, there is another safe, FDA-approved way to stimulate the same area in cocaine addicts, they say. It is transcranial magnetic stimulation, or TMS, which uses a portable, powerful electromagnet to deliver a magnetic pulse strong enough to evoke electrical activity in the brain. TMS has been used to treat depression.
“We don’t need to wait 10 or 15 years to possibly figure out what to give to patients as a therapy."
"We don't need to look for a drug," said the study's principal investigator, Dr. Antonello Bonci, scientific director of the intramural research program at the NIH's National Institute on Drug Abuse. Using an already-approved treatment such as TMS will shave years off the time it takes to get the potential treatment to patients. "We don't need to wait 10 or 15 years to possibly figure out what to give to patients as a therapy -- we have the ability now to set up clinical trials and hopefully try to help patients within a matter of months."
Bonci and his team think they could have a TMS clinical trial for cocaine addicts recruiting patients by the end of the year.
Their confidence stems from the somewhat stunning black-and-white nature of their results in rats, which were unheard of before optogenetics. Their study, published in April in the journal Nature, explained how rats trained to seek cocaine rewards were cured by a switch in the prefrontal cortex.
To produce a group of rats that closely mimic human addiction, the researchers first gave the animals free access to cocaine, which they could get by pressing a lever. Then they introduced mild shocks to the rats' feet at random intervals as a negative consequence of the drug use.
About 70 percent of the rats stopped pressing the lever when the shocks started. The rest, though, kept compulsively seeking the cocaine reward despite the unpleasant result; they were addicted.
"The addicted rats showed this silence in that part of the brain," Bonci said, which the researchers were able to measure electrically after the animals were euthanized. The prefrontal cortex, the area "silenced" by the cocaine addiction, correlates to the dorsal anterior cingulate cortex in people, he said.
"Human studies have shown that chronic cocaine abusers do have a very low productivity in that area," Bonci said. Both brain areas appear to be implicated in regulating the conscious control of decisions that either harm or benefit: In this case, should I take the drug, or not?
The addicted rats' brain cells in this area were then turned into on/off switches using the optogenetics technique. Researchers injected special light-activated proteins (called rhodopsins) targeted to that brain area by genetic manipulation, and implanted the tiny fiber optic cables.
With the flip of a switch, laser light from the fiber-optic cable turned on activity in the prefrontal cortex, and "within a matter of hours" the addicted rats were no longer addicted.
Even more amazing, perhaps, is what the group did to further prove that they were targeting the right area. They took the nonaddicted rats (the ones that stopped going after the cocaine when shocked) and used their method to turn off the prefrontal cortex area. The rats became addicts just as quickly.
"This is amazing," Bonci said. "It shows causality, that the activity of this brain region is clearly tied to this behavior, but also that the brain can go back to normal after months of exposure to something that is pretty toxic."
"[TMS] is cruder, but of course the advantage is that it's not invasive and you have nearly zero side effects," he said. "What matters for now is that we know what we should be doing in that brain region to try to reduce craving. We know what to do and we have proof that it should work."
And that's very good news for the millions of people struggling with addiction and for those who love them, too.
