Running electric current through the brains of cocaine-addicted mice can change the behaviors associated with their dependency, according to a study published today. The new therapy combines deep brain stimulation (DBS) with a drug treatment to normalize brain behavior in cocaine-addled mice, raising the possibility that similar approaches could one day be used to treat addiction in humans.
Researchers ran a series of four experiments using deep brain stimulation and a drug that blocks receptors for dopamine, a chemical messenger known for its involvement in addiction. Each experiment involved 60 to 80 mice, some of which were injected with cocaine; scientists monitored their behavior as they withdrew from the drug. Cocaine has been shown to make mice hyperactive, and a form of hyperactivity called locomotor sensitivity is used as a measure of how vulnerable mice are to addiction and relapse. In this study, locomotor sensitivity was determined after a "cocaine challenge," where scientists measured the distance each mouse ran through a circular corridor 10 days after injection.
"You need to know exactly what you need to achieve."
There was a point to all this. The aim of the study, published in Science, was to see if it was possible to develop a kind of deep brain stimulation to treat addiction; mice are the first step. The technique requires electrodes to be implanted in certain spots in the brain; then, they can be stimulated using a pacemaker-like device implanted under the skin. DBS is already used in humans — Medtronic’s device Activa is approved in both the US and Europe for treating symptoms of Parkinson’s and has been used by more than 100,000 people — but finding the right targets to jolt, as well as the right "dosage" of electricity is crucial. That’s where the mice come in.
Today’s study measured two frequencies of stimulation in the cocaine challenge. Scientists found that high-frequency DBS (130 Hz) suppressed the mice’s hyperactivity only temporarily, but low-frequency DBS (12 Hz), combined with a synthetic compound that blocks some dopamine receptors, made the mice behave normally. The study’s authors say they sought to develop a modified form of DBS therapy that would mimic the effects of optogenetic treatments, which allow scientists to control neurons with light.
Optogenetics has shown promise as a potential treatment for cocaine and alcohol addiction, but the techniques remain too risky to test on humans. Optogenetics is widely used in mice, which are genetically engineered to have certain neurons with light-sensitive proteins. These proteins, called opsins, make the neurons fire when a scientist shines a laser beam on them. Though optogenetics has made the jump to other primates, figuring out how to implant opsins isn’t easy. So neuroscience professor Christian Luescher and his colleagues at the University of Geneva decided to mimic the effect with existing technology: deep brain stimulation. Previous studies have examined the potential for DBS to cure addiction, but the disease is highly complex, and there’s still uncertainty over which parts of the brain to target with electric stimulation.
Experts say new therapy is "promising."
"What we would like to argue is you need a strong rationale," says Luescher, one of the study’s authors. "You need to know exactly what you need to achieve if you want to have a successful new therapy and a new indication for DBS."
In their study, Luescher and his colleagues found that when applied on their own, neither low-frequency DBS nor the synthetic compound, SCH 23390, had any effect on the cocaine-related behavior of the mice. When they were used together, though, the mice began behaving more normally within 24 hours.
Michael Stefanik, an postdoctoral research associate at Rosalind Franklin University, describes the findings as "promising," though he says more work is needed to determine whether it could have meaningful implications for drug addicts.
"Addiction is certainly much more complex than one behavior model that they’re using to present here," says Stefanik, who co-authored a paper on optogenetics and cocaine addiction, and was not involved in today’s study. "When you look at addiction as a whole, it’s really heterogeneous in terms of brain regions, in terms of the cells that are involved. The model is informative... but it doesn’t model all aspects of an addict’s life."
There’s also the formidable challenge of applying the technique to humans, whose brains are of course far more complex than those of mice. That caveat alone draws sharper skepticism from other experts.
"I wish I had one dollar for every animal study that promised to lead to a breakthrough treatment."
"I wish I had one dollar for every animal study that promised to lead to a breakthrough treatment for addiction [and] hasn't," Wayne Hall, a professor at the University of Queensland in Australia, said in an email. Hall, who has raised concerns over testing DBS on drug addicts in the past, also questions the long-term effectiveness of the therapy described in today’s study. "Addicted individuals cannot get access to less expensive treatments that work now," he adds. "Why waste money developing an even more expensive one that almost no one will... be able to use?"
Luescher acknowledges the limitations of his study and concedes that DBS is still far from mainstream. But he believes the therapy put forth today could nevertheless mark an important first step in treating addiction at its source.
"It’s not going to be a treatment for the masses, because it’s expensive and it’s quite challenging," he says. "You need a surgeon, you need a neurologist... these [DBS implants] are not cheap. But for some people, this may really be the solution."