LA JOLLA, Calif.—A heroin habit is extremely difficult to overcome, given how addictive the drug is, but a new option for countering the urge to use heroin has shown some promising results in animal models. The work comes out of The Scripps Research Institute, and was published in Neuropsychopharmacology in a study titled “High-Frequency Stimulation of the Subthalamic Nucleus Blocks Compulsive-Like Re-Escalation of Heroin Taking in Rats.”
The approach in question consists of applying low-level electrical stimulation to the subthalamic nucleus via implanted electrodes. While it's not entirely known what this part of the brain is responsible for, it seems to be able to modulate compulsive behaviors and abnormal muscle activity. DBS of the subthalamic nucleus is an existing treatment for the symptoms of Parkinson’s disease, and when applied in these patients, has been shown to reduce compulsive gambling and shopping. In addition, the U.S. Food and Drug Administration approved the use of subthalamic DBS to treat severe cases of obsessive-compulsive disorder in 2009.
The researchers worked with an animal model of heroin addiction in which rats are able to self-administer heroin by pressing a lever, for 12 hours per day over the course of two weeks. Generally, rats in such a scenario increase their heroin intake and demonstrate signs of addiction. When access to heroin is reintroduced after two weeks without it, the rats rapidly re-escalate their intake.
“It has been very difficult to reduce heroin-seeking and -taking in an animal model because heroin is such an addictive drug, but the results here are very impressive,” said Olivier George, an associate professor in TSRI’s Committee on the Neurobiology of Addictive Disorders and principal investigator of the study. “This is the type of preclinical evidence that one needs, in order to start testing this strategy in humans.”
“These results also suggest new insights into the neurocircuitry of heroin addiction,” added co-author George F. Koob, who led the Committee during the study and is on leave from TSRI to direct the National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health.
When rats received DBS, however, they kept their intake constant at a low level, while control rats who did not receive DBS re-escalated their drug usage after abstinence. When the DBS was switched off for two days, the DBS-treated rats began increasing their heroin usage like the control rats.
“It was really like an on-off switch,” George said. “Then two days later we turned it on again and their intake came back down.”
In another model, the rats were given shorter exposures to heroin and animals receiving DBS treatment again demonstrated lower intake levels than control rats. Treated rats showed significantly less motivation to use, giving up sooner when they had to press a lever an increased number of times for heroin to be administered.
The intensity of the DBS used was much lower than what is applied in the treatment of movement disorders, and given that the rats displayed normal physical activity, it's not expected to impair normal movement, according to George.
The team also looked at neuronal activity during DBS and found that the treatment worked by causing a net reduction in the subthalamic nucleus' activity, with several regions found downstream from the subthalamic nucleus also showing signs of reduced activity. Among those regions is the nucleus accumbens shell, which plays a role in creating the senses of “liking” and “wanting” pleasurable things and is thought to be part of the brain circuitry involved in maintaining addiction.
"We think that deep brain stimulation can be a useful non-drug intervention for treatment of addiction,” said Carrie L. Wade, a postdoctoral research associate in the George Laboratory during the study, now at the University of Minnesota.
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