Received: by alpheratz.cpm.aca.mmu.ac.uk id BAA02480 (8.6.9/5.3[ref pg@gmsl.co.uk] for cpm.aca.mmu.ac.uk from fmb-majordomo@mmu.ac.uk); Fri, 21 Dec 2001 01:40:55 GMT Message-Id: <200112210136.fBL1aF115444@sherri.harvard.edu> Subject: Re: Fwd: Eureka! Date: Thu, 20 Dec 2001 20:36:19 -0500 x-sender: wsmith1@camail.harvard.edu x-mailer: Claris Emailer 2.0v3, Claritas Est Veritas From: "Wade T. Smith" <wade_smith@harvard.edu> To: "Memetics Discussion List" <memetics@mmu.ac.uk> Content-Type: text/plain; charset="US-ASCII" Sender: fmb-majordomo@mmu.ac.uk Precedence: bulk Reply-To: memetics@mmu.ac.uk
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.
===============================================================
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