Rats that will go to great lengths to get a cocaine fix might blame a group of sluggish neurons. Controlling the problem may come down to a flick of a light switch: Stimulating those brain cells with lasers reduces the addicted rats’ cocaine use, researchers report in the April 4 Nature.
“It's an outstanding piece of work,” says neuroscientist A.J. Robison of Michigan State University, who wasn’t involved in the study. The findings could help researchers better understand the role of neural circuitry in drug addiction in humans, he says.
Scientists know that when certain neurons fire less frequently in the prelimbic cortex, a brain region that handles impulse control and reward-driven behavior, a person’s self-control can decrease. But researchers didn’t know whether using cocaine chronically could make the neurons drowsy to begin with, and whether that sluggishness could also promote drug use in spite of ill consequences.
Billy Chen, then of the National Institutes of Health, and colleagues trained rats to take cocaine. The rats learned to press levers to receive a dose of drug through an IV. After about two months, researchers started giving the rats shocks roughly one-third of the time when the animals pressed the levers. Most of the rats stopped taking cocaine, but about 30 percent continued. These were compulsive cocaine users, says coauthor Antonello Bonci, a neuroscientist at the NIH’s National Institute on Drug Abuse.
Then the researchers sent electric current through neurons in an area of the rats’ prelimbic cortex that links to other brain areas involved in drug-seeking behaviors. Neurons in all cocaine-using rats were less likely to fire in response to the currents than cells in rats that hadn’t taken cocaine. And compared to noncompulsive cocaine users, the compulsive users’ neurons needed almost twice as much current to fire. That means that the long-term cocaine use likely reduced neuron firing, especially in the compulsive users.
To find out whether those sluggish neurons in turn caused the compulsive behavior, the scientists turned to a technique called optogenetics, which uses light to turn neurons on or off. The researchers injected the rats with viruses that inserted light-responsive molecules into the lazy neurons. When the researchers used lasers to stimulate the neurons in the compulsive rats, the rats pushed the levers one-third as often. The same experiment on rats that hadn't been shocked had no effect.
The researchers then reversed that experiment, using lasers again but this time turning off the neurons in the non-compulsive users. Those rats started pushing the levers for cocaine almost as frequently as the other rats had.
The study doesn’t explain why some rats become compulsive users and others don’t, Bonci says. Still, researchers could use the findings to generate new treatments for compulsive drug use. The team hopes to conduct clinical trials on a potential treatment that energizes the sluggish neurons using transcranial magnetic stimulation, which applies an electromagnetic field to targeted areas of the brain.
Although the study was well done, it addresses only one component of addiction, says neuroscientist Peter Kalivas of the Medical University of South Carolina. Another component is relapse among previously addicted people. Other studies have found that silencing rather than stimulating neurons in the prelimbic cortex can prevent addicted rats from starting to use cocaine again after a period of abstinence.
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