Fixing the Fix – repairing the reward circuit in the brain, as part of addiction recovery

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Fixing the Fix

  • Courtney Humphries
JANUARY 22, 2015

Rerouting Habits

The reward circuit explains why drugs are addictive, but it does not explain why some people cannot stop, even if they want to. Drug-taking transforms from a chosen act into a habit, and eventually a compulsion. The behavior becomes entrenched and less accessible to conscious decisions. By imaging the brains of drug-addicted people, scientists have found differences in a part of the brain called the prefrontal cortex, a kind of executive decision-maker in the brain. Edythe London, PhD, director of the Laboratory of Molecular Neuroimaging at UCLA, says that addiction impairs the ability of this decision-maker to do its job. Addicts have problems with the interplay between responding to environmental cues and conscious control of their actions—an exaggerated response to reward—in the prefrontal cortex, she says.

The reward system itself also becomes damaged over time. In those who abuse stimulants, less dopamine is released as abuse continues, so the addict needs to use more to get close to the first-time experience, when a greater surge of dopamine was released. Meth causes even more destruction. It opens the door for dopamine to exit the vesicles where it is stored in the cell and enter the synapses, where it auto-oxidizes, damaging cells.

Peter Kalivas, PhD, a neuroscientist at Medical University of South Carolina, says that scientists are excited about creating new treatments that target the brain changes that mire many people in their addictions. “The treatment should really be focused on relapse, and the vulnerability to relapse,” he says. In animal studies, scientists have found that brain areas involved in learning and habit formation become more active as an addiction progresses. Kalivas, like London, points to the prefrontal cortex, which Kalivas says normally can modify habit circuitry. Even though you habitually take a certain route to work, for instance, your prefrontal cortex can help decide on a better route if there is a traffic jam. When someone is addicted to a drug, Kalivas says, he may receive “error messages” telling him to alter his behavior—a spouse threatens to leave, or he falls behind at work. But somehow, these messages do not lead to behavior change. “The addict can tell you what’s wrong, they just can’t use that information,” Kalivas says. “Through cortical intervention most of us can make a plan to change the habit or adapt it. But addicts are not able to do that.”

Can we give someone better self-control in a pill? It may seem far-fetched, but many scientists believe something like this is possible. Kalivas’s research has focused on glutamate, a chemical signal in the brain that is important for allowing the prefrontal cortex to change habits. His lab found that drug-addicted animals lack the ability to alter the connections between the prefrontal cortex and a part of the brain’s habit circuitry called the basal ganglia, a changeability called synaptic plasticity. The defect seems to stem from an inability to clear glutamate out of synapses, the junctions between neurons. Normally, the chemical is released in a specific location by neurons in the synapse and then quickly vacuumed back into nearby supporting cells called glia, resulting in a brief chemical signal at a specific synapse. In drug addiction, he explains, the glia lack the ability to vacuum glutamate away.

Kalivas’s lab has been studying molecules that help promote the transport of glutamate back into cells. One of them turns out to be a common antioxidant health food supplement, called N-acetylcysteine (NAC), which is being tested as an addiction treatment in cocaine users and cigarette smokers.

Another way that medications might aid a recovering addict is by targeting serotonin. Though the neurotransmitter is best known for its role in depression, Kathryn Cunningham, PhD, a pharmacologist at the University of Texas Medical Branch at Galveston, is leading a new federally funded center that will investigate molecules targeting the brain’s serotonin system as potential addiction treatments. She says that an imbalance in serotonin seems to have a role in behaviors that cause people to relapse. “We’re trying to understand the biology of what’s driving the relapse,” she says, “and trying to help alleviate some of those issues.”

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