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Short-Circuiting Addiction

April 10, 2002

Heather Heilman

Wouldn't you like a reward? It seems like a good and desirable thing, but when neurocircuits in a drug-user's brain "reward" a person for using tobacco, heroin, or any other habit-forming substance, an addiction is born.

"All drugs of abuse appear to target the same kind of rewarding mechanism in the brain," said Richard Harlan, professor of structural and cellular biology. "That's why they're all addictive, because they all activate this reward circuit. So people try to duplicate the experience of taking the drug."

Harlan is the director of the new Tulane-Xavier Center for Substance Abuse Research and Prevention, which brings together researchers from Tulane, Xavier and Louisiana State universities who are trying to understand how addiction works and find ways to short-circuit it. The center is funded by a five-year grant from Louisiana's Health Excellence Fund, which distributes money from the state's tobacco lawsuit settlement.

Tulane pitched in money for new equipment. While each researcher will be working on his or her individual project, the center will bring them together to find the links between their work. Using rats that have been conditioned to expect morphine in a particular environment, Harlan hopes to find a way to decrease the rewarding properties of opiates through the use of pharmaceuticals.

"We're going to try a variety of different agents, including drugs that interfere with serotonin mechanisms and drugs that are similar to those used to treat epilepsy," he said.

A colleague at Xavier, Tarun Mandal, is looking at ways to put those pharmaceuticals into microcapsules that could be implanted under the skin, allowing for prolonged release. Such a device, implanted in addicts, could decrease their desire to seek drugs. Harlan will also be looking at the brains of the rats to see if there's something different about those that expect the reward of morphine in a particular environment compared to those that don't expect it.

He hopes to gain insight into addictive personalities--those people who are more susceptible to the addictive properties of drugs. He also wants to look at the neurocircuits that are activated simply in response to the environment where the morphine is administered.

"That's clinically relevant because people become addicted to the environment as much as to the drug itself," he said. "You can detox someone and put them back in the environment where they were taking drugs, and, bingo, they're right back in it."

Meredith Garcia, Harlan's colleague and spouse and an associate professor of otolaryngology, will be studying the neural circuitry and chemistry involved in those processes. Jim Zadina, adjunct professor of medicine, will look at neuropeptides that bind to the same receptor as morphine and that might be useful at controlling pain while being less addictive than morphine.

"One of the major problems of trying to treat pain with opiates is the fear that people will get addicted," Harlan said. A related question is how to treat pain in addicts, which will be studied by Dennis Paul of LSU's pharmacology department.

Harold Komiskey at Xavier will study the effect of psychostimulants--like methamphetamines--on the brain. And Wayne Harris, the dean of the pharmacy college at Xavier, will examine the prevalence of prescription drug abuse in New Orleans and try to develop an educational strategy that could reduce it.

"I think a lot of patients have no real understanding that if you're prescribed one pill a day and it does something good for you, then taking two or three could be very dangerous or addictive," Harlan said. Harlan, who has been studying addiction for 15 years, is aware of the depth and complexity of the problem but is confident he and his colleagues can make a difference.

"The way I look at this, drug abuse has such an enormous impact on society that if you could reduce it by even two percent it would have a huge benefit to society," he said. "Anything we can do will help."

Heather Heilman may be reached at hheilman@tulane.edu.

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