WITHDRAWAL MEMORIES CAN RENEW DRUG-SEEKING ACTIVITY

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NR-01-05 (02/01/05). For more information, please contact Dawn McCoy at (202) 462-6688 or dawn@sfn.org.

WITHDRAWAL MEMORIES CAN RENEW DRUG-SEEKING ACTIVITY

WASHINGTON , DC February 1, 2005 — Memories of drug withdrawal can activate part of the very brain circuits that created withdrawal in the first place, possibly leading to drug relapse, according to a study published in the February 9, 2005, issue of The Journal of Neuroscience. The finding could lead to new or better treatments for withdrawal syndromes.

François Frenois, PhD, of Université Victor Segalen Bordeaux 2 in France, and colleagues analyzed the brains of rats that had been addicted to morphine, denied access to the drug, and then re-exposed to the environment where withdrawal was experienced.

“This paper defines regions of the brain that are important for memories of withdrawal in rats, providing new insight into the development of new treatments for withdrawal syndromes in humans,” said Eric Nestler of the University of Texas Southwestern Medical Center at Dallas.

Frenois and his team compared the neural pathways activated during both the initial formation and subsequent retrieval of withdrawal memories. They analyzed the activity of a gene called c-fos, an indicator of stress and adaptation. Drugs and other stimuli can trigger c-fos expression and alter long-term brain function—even if used only once. In this study, the stimuli used were a precipitated withdrawal from morphine (implanted as pellets under the rats' skin) or an environment previously associated with withdrawal.

Once the rats had been treated with morphine, the authors used a Y-shaped maze to condition the rats to different stimuli. In one branch, rats were injected with naloxone to induce morphine withdrawal; in the second branch, inert saline was injected. The time the rats spent in each branch of the maze was noted—as were areas they avoided—allowing the scientists to gauge the rats' aversions to parts of the maze and the associated stimuli. The environmental features of the room in which the maze was placed also influenced rat behavior. When rats were returned to the withdrawal area of the maze, brain responses were measured.

The scientists compared the brain readings of these rats with baseline data of brain activity during initial withdrawal. They then observed which parts of the brain were involved during the process.

The team found that re-exposure to an environment associated with withdrawal reactivated part of the withdrawal neural circuitry, which can drive behavioral changes causing drug relapse. Addiction, the authors say, is a chronic, recurrent disorder involving motivation, emotion, and memory. Frenois and his team say their work is an important step in helping to determine how specific environments associated with drug withdrawal might encourage drug seeking.

The Journal of Neuroscience is owned and published by the Society for Neuroscience, an organization of more than 36,000 basic scientists and clinicians who study the brain and nervous system. Corresponding author Catherine Le Moine can be reached at 33-0-5-57-57-17-78 or at catherine.lemoine@umr5541.u-bordeaux2.fr.