Meth and Memory

Student-faculty research may yield drug-addiction remedy

by Michelle Simmons

January 26, 2011

André White ’11 (right), an international student from Jamaica who has been working closely with psychology professor Tony Rauhut for two years, plans to go into neuropharmacological research. “I love the freedom, the ability to innovate,” he says.

With a new year come new resolutions—to quit smoking being among the most popular. As many former smokers know, however, getting through nicotine withdrawal is just the beginning. Quitters also need to change their environment and get rid of any lurking reminders of the habit.

According to Tony Rauhut, associate professor of psychology, there’s a reason for this: classical conditioning. “Cues that are predictive of a drug come to produce cravings themselves,” he explains. “When you quit, your brain remembers cues in the environment that are associated with the drug. When you experience those cues, they elicit cravings.”

Rauhut, who’s studied nicotine addiction for nearly a decade, has been working on finding ways to dampen the effects of those cues, through researching the brain’s learning process and its capacity for memory and association. And since 2008, he and neuroscience major André White ’11 have studied a much more addictive and insidious drug: methamphetamine.

Stimulating findings 

Rauhut and White are examining something called methamphetamine-conditioned hyperactivity in mice. Because methamphetamine is a stimulant, “when you give an animal the drug, it begins to run around and around,” says Rauhut. “It’s also associating the drug with the environment, which in this case is a locomotor-activity chamber. Over time, you can place the animal in the chamber, and it’s going to run around and around without the drug.”

White is studying a specific contributor to that hyperactivity, the neurotransmitter norepinephrine, which interacts with different receptors in the brain. “A receptor-neurotransmitter is like a lock and key,” says Rauhut. “Here’s the receptor, and you’re going to have some neurotransmitter or drug that can fit into that lock.”

One of those keys is an alpha-blocker drug called Prazosin, used to treat high blood pressure. It also dulls the emotional effects of painful memories and is prescribed to sufferers of post-traumatic stress disorder (PTSD).

“There’s a lot of overlap between drug addiction and an anxiety disorder like PTSD. It’s a new way of thinking about addiction,” explains Rauhut. “We’re targeting the maladaptive memory—whether it’s a bad memory in the case of PTSD or a really good memory in the case of drug addiction.”

Checking memory      

In a series of experiments, White and Rauhut gave one group of mice Prazosin before injecting the methamphetamine and another group the drug immediately afterward. “We began with testing to see if the Prazosin had any effect on the mice and what that effect would be,” says White.

The result so far? According to White, Prazosin blocks the mouse’s brain from linking the locomotor-activity chamber with that shot of methamphetamine, thereby blunting its learned—or conditioned—response.

But there’s only a small window of opportunity. Prazosin has to be injected within 24 hours to be effective, says White. His honors research project, he adds, will “fully define that window—when the drug is active and when it is not.”

Finding application 

Rauhut says that clinical applications include finding drugs like Prazosin that counteract the learned-response component of addiction. But there’s a lot more to study. The next steps are to try similar experiments to examine if other types of receptors, such as the alpha-2 or beta, are involved in the process.

“This is a big issue in drug-addiction research,” says Rauhut. “You want to find a drug that is specific to treating the addiction and not make the person an emotional vegetable. You want these individuals to experience pleasure; you want them the preserve other memories.”

Rauhut and White have presented a poster on their preliminary findings at the Society for Neuroscience annual meeting two years in a row. Rauhut anticipates that their research will culminate with publication in a peer-reviewed journal. “This doesn’t happen with every project,” he says. “Sometimes things work out really well; other times they don’t. With André, he’s been in the lab for so long doing this series of related experiments, his work will be published.”