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Rewiring the Brain against Addiction

Scientists are discovering brain chemistry that prevents, and reverses, addiction.

By Jeffrey Helm 1 Jun 2006 | TheTyee.ca

Jeffrey Helm, a former neuroscientist, writes about science issues for The Tyee.

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Stopping craving 'upstream.'

What if you could take a drug that would cure addiction?

While some look for answers to addiction in religion, 12-step programs and the power of positive thinking, scientists are pushing forward the frontiers of neurobiology.

Researchers are figuring out how addiction rewires the brain. The goal is to eventually be able to rewire an addicted brain back to the way it was, before the drugs, the cravings, and the self-destruction.

Before we get to the research, some brain science basics to digest:

Humans take addictive drugs for the same reason they take aspirin when they have a headache: they want to feel better. For many, drug use begins as a release, a euphoric detachment from fears, pain, and troubles. But with each use, a wire is threaded in your brain, a wire that connects the drug to the varied list of things that you need and want. With each use the connection grows stronger and the list shrinks until eventually there is one want and one need that is greater than all others: drugs.

Dopamine is a central chemical in addiction that rules the pleasure and motivation system of the brain, making our biological drives, like eating and sex, enjoyable. Practically all addictive drugs increase dopamine and have a "feel-good" aspect to their effects. As a result, the dopamine circuitry that governs motivation and reward is the focal point of most addiction research.

But the dopamine system cannot explain all the features of addiction on its own. So researchers are trying to find out all they can about a brain chemical called orexin.

Blocking addiction upstream

New research published in Neuron by a team at the University of California looked at how orexin triggers the brain circuitry that increases arousal and gets you craving good things like food and water. This circuitry is upstream from the pleasure pay-off of dopamine. It is the craving before the feel-good.

Craving is a big part of addiction, so researchers looked at whether orexin is playing a part in wiring addiction.

The University of California team knew that when you give doses of cocaine to rats over time, the rats respond with higher and higher levels of physical activity. "You give [the drug] over five days and the animals run around more and more," Dr. Stephanie Borgland, the primary author of the research, told The Tyee.

This running around is more than an immediate reaction to the drug. It is an escalating expression of dependency and craving that models features of addiction in humans. In short, it is observable evidence of the addiction circuitry.

Researchers call this process "sensitization" to the drug.

This sensitization circuitry remains in place long after the drugs are no longer in the body -- part of the reason that an addict, even after laying off drugs for a long time, can be hooked again with a single dose.

But this sensitization won't occur if, at the beginning of cocaine use and throughout, the same brain is also dosed with a chemical that blocks the flow of orexin.

Borgland's research team came to this conclusion after giving regular doses of cocaine to two sets of rats. One group also received an orexin blocker, delivered through a tube directly to their brains.

Rats that received the orexin blocker before each cocaine injection did not develop a sensitization to cocaine.

The researchers conclude that blocking the activity of orexin in the brain when cocaine exposure was started prevented cocaine from wiring addictive behaviour into the brains of the rats.

The findings raise some interesting questions that would have to be addressed if therapeutics based on this research were developed for humans.

What if we were able to develop a "blocker" that allowed people to take highly pleasurable drugs like cocaine without becoming addicted?

Would more people use cocaine, which has other bad health effects?

Would an addiction blocker make the prescription of addictive medical narcotics, like codeine and oxycotin, less risky?

How would such a "blocker" change our society's relationship with currently addictive drugs?

Reversing addiction?

The University of California experiment with an orexin blocker points towards a way to prevent the wiring of the brain for addiction. But orexin blockers would not be able to fix rewiring once it occurred; they could help you from getting addicted, but once you were hooked they wouldn't help.

How, then, might addiction get wired out of the brain? That is the question being pursued by a research team out of UBC. And they may be on the verge of an answer.

"[Our research] is aimed at restoring the connections in the brain that may have existed before the exposure to the addictive substances," said Dr. Karen Brebner, neuroscientist and co-author of research recently published in Science.

The UBC research team thought that addiction could get wired in the brain just like a normal memory would be. So they took their knowledge of how memory works in the brain and applied it to the same behavioural test that was used in the orexin study.

"We found that blocking one type of rewiring in normal memory formation also plays a role in the formation of rewiring in drug addiction," said Dr. Tak Pan Wong, co-author and researcher at UBC's Brain Research Centre.

The UBC team noted that one way memories come into being is when neurons change their firing to a slow and steady pulse to alter circuitry in the brain. The UBC team made a very, very small protein fragment that prevents the change in rate of firing and thus blocks the formation of a circuit that could form a memory. The researchers tried their memory-blocking protein on mice that had been getting injections of amphetamine.

The UBC team believes it worked as they had hoped. The mice "looked like animals that were receiving the drug for the first time," said Dr. Brebner.

The protein made mice that were like addicts behave like mice that never had amphetamine before. When the signalling that was responsible for reinforcing the addictive behaviour was shut down, the addictive "memory" was erased. Which means that the protein that the UBC team made could potentially reset the wiring in the brain that is responsible for the cravings that remain long after the drugs are gone.

Decades away?

Medications based on blocking orexin might be available to people within a few years since drugs working on the pathway are already being tested in humans with sleeping disorders.

However, addiction reversal therapies based on the UBC research are going to be a much longer wait. Researchers don't expect to see human applications for at least 15 to 20 years.

Resetting the addicted brain to a non-addicted state could help a lot of people get off destructive drugs and stay clean.

Currently there is very little that medicine can offer addicts, other than dulling the chemical rush or treating the symptoms of withdrawal. Just ask Mike. No medical treatments helped him kick drugs. Now middle aged, Mike has been clean for seven years. His struggle with addiction started in his teens with cocaine and then moved to heroin once he came to Vancouver.

Withdrawal was hell. "It's like your worst flu times 50," said Mike. He didn't sleep for a month. He lay in his bunk at the recovery house and watched a traffic light change colour while his bones ached and his body cried out for heroin.

Mike has heard about medications that block cravings before, but he is not optimistic.

"I think that if you don't get it right in your heart and realize that you need to make a change...then you will never, ever get well," said Mike. "What works is getting honest and actually looking at the problem and realizing and shedding any reservations you might have."

Jeffrey Helm, a former neuroscientist, is writing about science issues for The Tyee this summer.  [Tyee]

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