June 26, 2000 Every day, thousands of drug, alcohol and tobacco addicts relapse when they are exposed to simple, seemingly harmless reminders of past experiences. But what causes the powerful cravings underlying this huge relapse problem? UW Medical School researchers are one step closer to the answer. They've found that the memory of drug use can alter an area of the brain not traditionally implicated in addiction. The study appears in the August issue of Synapse (published June 21).
"Our study with rats showed that environmental cues associated with drug use can produce profound molecular changes in brain circuits linked to learning and decision-making as well circuits related to emotion," said Ann Kelley, UW Medical School professor of psychiatry. "The changes in cognitive regions may contribute significantly to the craving that is thought to play such an important role in relapse."
Kelley and graduate student Brock Schroeder injected rats with morphine once a day for 10 days. The injections were administered in a cage that was different from where the animals normally lived. The cage came to represent the "drug environment."
The researchers monitored the animals' motor activity, which increased with the administration of drugs. When the treated rats were later placed in the drug cage without being injected, they still showed increased movement, proving they had been conditioned to the environment.
Tissue from the brains was then scanned microscopically for signs that the gene called Fos was being produced, a technique used to precisely pinpoint brain activity. As expected, the scientists saw increased Fos expression in the limbic circuits, including the nucleus accumbens. They were surprised to find, however, that particularly strong Fos expression also occurred in the prefrontal cortex, the portion of the brain that's crucial to making rational decisions about behavior.
"We found that drug reminders have the ability to induce powerful physiological responses in learning and memory systems," said Kelley. "Long-term changes may persist in these critical areas, particularly in people who self-administered drugs for long periods of time."
The Wisconsin study is the first to show that cues associated with opiate drugs trigger Fos expression in cortical brain regions.
"Growing evidence suggests that abused drugs of different classes--opiates and stimulants--affect common pathways," she said, adding that experiments under way in her laboratory are showing that sensory cues linked to nicotine and palatable food also affect the same brain systems.
Once scientists learn more about the molecular mechanisms underlying the craving state, pharmaceutical companies can begin designing drugs to block or override it, said Kelley. She's hopeful that the new finding may also encourage cognitive-therapy approaches to addiction, which entails learning to think differently about personal problems.
"Since we now know that the circuits that are pertinent in this kind of therapy are also affected by exposure to drugs, it's possible we can teach addicted people to cope more effectively with craving when it first comes up," she said.
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