Re: Fwd: Eureka!

From: Wade T. Smith (wade_smith@harvard.edu)
Date: Fri Dec 21 2001 - 01:36:19 GMT

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    Hi Philip Jonkers -

    >Also it makes sense for the brain to reward events of
    >relief of confusion as it so reinforces/encourages
    >attempts to resolve future events of confusion.

    From SciAm online-

    - Wade

    *********

    Beating Abuse

    -By Tabitha M. Powledge

    Glutamate May Hold a Key to Drug Addiction

    http://www.sciam.com/2002/0102issue/0102scicit5.html

    Addiction has long been thought to be a form of learning. In the past few
    years, molecular biologists have amassed chemical evidence to prove it,
    in the process generating new ideas for combating drug use.

    Some of the most striking recent studies have examined the affinity
    between cocaine and glutamate, one of several chemical neurotransmitters
    that govern communication between nerve cells and are involved
    particularly with memory. For example, Stanislav R. Vorel and his
    colleagues at the Albert Einstein College of Medicine discovered that
    electrically stimulating the hippocampus, a brain structure central to
    memory and rich in glutamate, causes dependence relapse in rats formerly
    addicted to cocaine. Other researchers found that glutamate activates
    brain cells devoted to dopamine, a neurotransmitter associated with
    feelings of reward and pleasure. Indeed, the dopamine reward circuit in
    the brain has been regarded as the addiction pathway, commandeered not
    just by cocaine but by all addictive drugs. The fact that glutamate
    modifies dopamine action demonstrates a direct connection between brain
    reward circuits and those for learning and memory.

    The reward and memory systems may harbor the secrets to addiction, but
    they also serve as a barrier to developing treatments. Altering either of
    these fundamental brain circuits without subverting some essential
    function is tricky business. "That's why there was excitement about the
    possibility that the glutamate system might be involved. But at this
    point, we're not there," says Francis J. White, a pharmacologist at Finch
    University of Health Sciences/The Chicago Medical School.

    A discovery published in September 2001 may nudge that process along.
    Researchers studying mice identified a particular glutamate receptor,
    known as mGluR5, that is crucial for cocaine dependence. Mice that lack
    the receptor do not become dependent no matter how much cocaine they are
    given. The mGluR5 findings are significant in part because the receptor's
    action appears to be selective. The mutant mouse takes food and water
    just like other mice, which suggests that lack of the receptor does not
    affect "natural" rewards, only interest in cocaine.

    Eliot Gardner, a senior research investigator at the National Institute
    on Drug Abuse, identifies two major hurdles to basing addiction
    treatments on glutamate. The first is figuring out which glutamate
    receptors are involved. (Even if mGluR5 is related to human cocaine
    dependence, it is not the only receptor significant in addiction.) The
    second problem is glutamate's ubiquity. "It's found all over the brain in
    lots of circuits subserving lots of behavior and mental processes that
    one would not want to manipulate," Gardner says. Researchers will need to
    find precise delivery systems that will target only specific brain
    circuits, leaving alone the dozens, or perhaps hundreds, of other
    circuits that use glutamate as a neurotransmitter.

    Intriguingly, the glutamate studies could strengthen that old
    nonpharmaceutical standby: behavioral therapy. One of the most promising
    treatments "is to have people unlearn aspects of addiction and relearn
    new things to do in life," says renowned molecular biologist and
    addiction specialist Eric J. Nestler of the University of Texas
    Southwestern Medical Center. "An argument can be made that Alcoholics
    Anonymous provides that type of alternative focus." Or pharmacotherapies
    could be combined with "talking cures" to yield fewer relapses. "If we
    could develop medications that could address the underlying biology, the
    powerful biological forces that drive addiction, then we can make a
    person more amenable to other treatments," such as behavior therapy,
    Nestler says. "You really need both."

    DRUGS FOR DRUG ABUSE
    The hunt for addiction treatments grows more intense every year. The
    National Institute on Drug Abuse is conducting clinical tests on more
    than 60 compounds for cocaine and opiate dependence alone and also a few
    for methamphetamine, according to Francis Vocci, who directs NIDA's
    Division of Treatment Research and Development. In addition to some
    compounds that act on glutamate and dopamine, researchers are looking at
    other targets. Chemicals that block the action of stress hormones are
    effective against opiates, cocaine, amphetamines and alcohol, Vocci
    reports, which means that a magic bullet that works against mechanisms
    underlying all addictive drugs is not utterly out of the question.

    ===============================================================
    This was distributed via the memetics list associated with the
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