March 14, 2005
Rats May Experience Cravings When Put In Drug Withdrawal Environment

When rats are returned to the environment where they withdrew from an addictive drug the brain circuitry that recalls drug withdrawal memories was activated.

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.

Being reminded of the withdrawal episode caused rats to reactivate circuitry in ways analogous to how the brain functioned while going through withdrawal.

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.

There are two obvious ways this knowledge could be utilized. First off, a drug that prevents memory formation could be used during addictive drug withdrawal in order to prevent a person from being able to later recall the experience of withdrawal. Then there would be no chance of cravings for the addictive drug from being intensified by remembering the withdrawal experience. This is a pretty drastic measure. But if it would help a person stay off something really damaging like methamphetamine it might be worth it to some people.

Less radically, a person about to go through withdrawal could be put in an environment very unlike any environment that person usually spends time in. That way the odds of encountering environmental cues that would recall the withdrawal episode could be decreased. The challenge then would be to figure how to construct an environment that would be least likely to be recalled by a later set of environmental stimuli. One difficulty in developing such an environment is that movies and TV shows present a much larger set of environments than most people would encounter in their own lives. Perhaps sensory deprivation environments would be best. But then just turning out the lights to go to bed might serve as a trigger to recall withdrawal. Total inability to recall withdrawal would be a far more certain method to prevent reactivation of the withdrawal response in the brain.

In the future withdrawal will be greatly helped by a number of therapies that are in the pipeline. Vaccines that cause the immune system to attack and destroy addictive drugs will reduce the satisfaction from using addictive drugs. Also, gene therapies and cell therapies will modify the brain to make it less prone to craving a drug in the first place.

Share |      Randall Parker, 2005 March 14 02:35 PM  Brain Addiction

Mark said at March 14, 2005 9:25 PM:

What I make of the whole chapter of addiction is that its all in the mind. A person can become totally free of any kind of addiction if his brain is conditioned into believing that there is nothing link addition.

Patrick said at March 15, 2005 11:52 PM:

It's been widely known in the drug treatment area that to keep an addict off drugs it is important to keep them away from the friends, family and surroundings they used to take drugs in.

Of course this is really hard.

dude said at March 16, 2005 10:06 AM:

What I make of the whole chapter of addiction is that its all in the mind. A person can become totally free of any kind of addiction if his brain is conditioned into believing that there is nothing link addition.

This may apply to drug cravings that occur long after one has quit, but almost any drug of abuse has definite withdrawal symptoms, including physical symtoms for many drugs as well as severe psychological symtoms (dysphoria, depression, anxiety, hostility).

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