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Interviewee: Christopher Cowan,
Pan Fried Brain
Drop an egg in a frying pan and who doesn’t think “Your brain on drugs”? But in the 21 years since that image became an icon, science has tried to learn what really changes in an addicted brain.
Animal studies have shown that tiny branches coming off of brain cells, called dendritic spines, are more abundant in addiction. These spines serve to create connections for increased communication across the gaps or synapses between brain cells. For years researchers believed that they were causing addictive behaviors. Now new research challenges that notion.
“They may actually be a brain mechanism to compensate, to try to limit, the individual’s sensitivity to the sort of maladaptive changes that lead to very long-lasting aspects of addiction,” says Christopher Cowan, an addiction researcher at the University of Texas Southwestern Medical Center.
For the last few years, Cowan has been studying the role of a certain family of proteins, collectively called MEF2, that are responsible for regulating the growth of dendritic spines as the brain develops over time. But Cowan also suspected that these proteins could perhaps be responsible for the growth of spines in addicted brains.
Says Cowan, “I wanted to ask whether, in an adult organism, an adult animal, particularly and ultimately in humans, whether these… changes in synaptic connections that are controlled by MEF2, whether these could be involved in the process of drug addiction.”
These proteins can be found in the reward or pleasure center of the brain, an area called the nucleus accumbens. This is the area in rodents, and presumably humans, where dendritic spines show increased growth when exposed to addictive drugs like cocaine. Cowan believed that MEF2 might be the culprit behind the spiny growth in this area, which would in turn be behind the incidence of addictive behaviors.
He and his colleagues ran a series of experiments, and found that in rodents, exposure to cocaine reduced the activity of MEF2, which then increased the growth of the spiny brain connections. When they tested the rodents who showed the increased spiny growth, these rats and mice exhibited more intense and long-lasting behaviors associated with addiction, such as restless motion and preference for places associated with the drug.
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These results seemed to support the popular hypothesis, so Cowan figured that not decreasing, but instead increasing the activity of the protein MEF2 would lessen both the growth of spines and the incidence addictive behaviors. He and his team created a modified version of the MEF2 protein that made it constantly active when inserted into the brains of his rodent participants.
But as he wrote in the journal “Neuron,”Cowan found quite the opposite from what he expected.
“Rather than inhibiting the addiction related behaviors, it actually enhanced those behaviors,” he says.
Your Brain Against Drugs
Cowan believes the growth of spines may actually be the brain’s way to fight the long-term effects of addiction. By fluctuating the levels of activity of MEF2 in the nucleus accumbens, and accelerating the growth of the dendritic spines, the brain may be trying to ameliorate the damaging and intense effects of addiction on the brain, including the exhibition of addictive behaviors.
Cowan proposes that, “The brain has some natural mechanisms, or natural processes that try to limit this change in brain function, as it relates to addiction.”
Cowan hopes further research into the role of the MEF2 protein in this process could lead to new drugs that actively combat the problem of addiction. Right now there are only a limited number of behavioral therapies for addicts, many of which are not very effectual. With a better understanding of how the brain naturally fights the effects of drug addiction, Cowan hopes that we can develop artificial ways of replicating the same process. It all hinges on understanding MEF2, but Cowan is hopeful.
“This gives us good therapy targets, to be able to go in and try to manipulate the function of those proteins, to try to antagonize or reverse the process of addiction,” he says.
PUBLICATIONS: Neuron, August 2008
RESEARCH FUNDED BY: Whitehall Foundation, National Institute of Drug Abuse, National Institute of Mental Health
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