Drug info - Cocaine addiction could be genetic, new study claims

[klaatu]

Mar 17 2006
ICLiverpool.com

PEOPLE'S chances of becoming hooked on cocaine may be inherited from their parents, a major international study has found.

The project, which included researchers from Liverpool, discovered a gene that directly affects the risk of someone developing an addiction to the Class A drug.

Teams tested 700 cocaine users and 850 non-users in Brazil, where crack and cocaine use is widespread.

Those who had a particular variant of a gene called the Dopamine Transporter (DAT) - around 30% of those tested - were more likely to become dependent on cocaine.

A very small number who had two copies of the DAT gene, one from each their mother and one from their father, were 50% more likely to become addicted.

Previous studies have found cocaine weakens the DAT's ability to help control the amount of dopamine in the body, giving the effect of a drugs "high".

Professor John Quinn, from the University of Liverpool, said the research proves much of a person's desire to use, and re-use, cocaine depends on their genetic make-up.

He said the research could now help develop drugs to treat cocaine addiction, and help understand the effect of other addictive substances, including alcohol and tobacco.

He said: "Genes are passed on from our parents, so if your mother and father both had this gene and were cocaine users, then you could be at a high risk of becoming dependent."

The study, being hailed as one of the most important-ever in understanding addiction, is published this week in the online edition of PNAS, the journal of the American Academy of Sciences.

It was carried out in conjunction with the Medical Research Council (MRC) Social, Genetic and Developmental Research Centre at the Institute of Psychiatry, King's College, London.

Dr Gerome Breen, lead investigator, said: "This study is the first large-scale search for a genetic variant influencing the risk of developing cocaine addiction or dependence.

"The target we investigated, DAT, is the single most important in the development of cocaine dependence.

"It makes sense that variation within the gene encoding DAT influences cocaine dependence."

Researcher Camila Guindalini, who analysed the gene, said: "It helps our understanding of the development of cocaine addiction.

"It could influence the design and use of drugs to treat cocaine abuse in the future.

"This means that, although repeated exposure to cocaine will lead to compulsive use in everyone, it seems some people will become addicted to the drug more quickly than others because of a genetic difference."

Professor Dr Homero Vallada, from the University of Sao Paulo Medical School, collected the samples with Prof Dr Ronaldo Laranjeira, of the Federal University of Sao Paulo.

He said: "It would be our hope that this is the first of many findings showing how genes, as well as environment, contribute to our risk for addiction.

"We think this may help predict pharmaceutical drug response for our cocaine addiction patients, but also how they might respond to different forms of psychological therapies."

Reputation Comments on this post:

Great substance for conversation. Thanks for giving me something to read and research about! I MEAN THANKS FOR GIVING ...

[Richard_smoker]

I'm sorry to quibble about things, but doesn't this new research oppose the current scientific view of DAT's role in cocaine addiction?? I was under the impression that DAT was once thought to be the central component to cocaine addictive properties, but has been since disproven by several studies. Here are just a couple of studies that are both several years old, and they assess the currently-held view that DAT isn't as important as we once thought it to be. I wonder what the deal is with this posting?? Was this taken from a scientific journal or is it just like a newspaper article or something??

Sorry to slam on your post, it's just that I don't believe that its claims are based on reality. As far as I know, these are old, out-dated beliefs based on a simplified view of the dopaminergic nucleus accumbens & prefrontal region.

Cocaine and Amphetamine Increase Extracellular Dopamine in the Nucleus Accumbens of Mice Lacking the Dopamine Transporter Gene.
by Carboni E, Spielewoy C, Vacca C, Nosten-Bertrand M, Giros B, Di Chiara G. Department of Toxicology and Consiglio Nazionale delle Ricerche Center for Neuropharmacology, University of Cagliari, 09126 Cagliari, Italy, and Neurobiology and Psychiatry Faculte de Medicine de Creteil, 94000 Creteil, France
J Neurosci 2001 May 1; 21(9):RC141

ABSTRACT

Behavioral and biochemical studies suggest that dopamine (DA) plays a role in the reinforcing and addictive properties of drugs of abuse. Recently, this hypothesis has been challenged on the basis of the observation that, in mice genetically lacking the plasma membrane dopamine transporter [DAT-knock out (DAT-KO)], cocaine maintained its reinforcing properties of being self-administered and inducing place preference, despite the failure to increase extracellular dopamine in the dorsal striatum. Here we report that, in DAT-KO mice, cocaine and amphetamine increase dialysate dopamine in the medial part of the nucleus accumbens. Moreover, reboxetine, a specific blocker of the noradrenaline transporter, increased DA in the nucleus accumbens of DAT-KO but not of wild-type mice; in contrast, GBR 12909, a specific blocker of the dopamine transporter, increased dialysate dopamine in the nucleus accumbens of wild-type but not of DAT-KO mice. These observations provide an explanation for the persistence of cocaine reinforcement in DAT-KO mice and support the hypothesis of a primary role of nucleus accumbens dopamine in drug reinforcement.

Cocaine Reward Does Not Require Dopamine or Serotonin Transporters--The Brain Sites Previously Implicated
EMBARGOED FOR RELEASE, Mona Brown & Sheryl Massaro. NATIONAL INSTITUTES OF HEALTH, June 22, 1998.

Cocaine's action in the brain requires more or other sites than researchers previously believed, or an unidentified means of action, according to scientists at the National Institute on Drug Abuse (NIDA), National Institutes of Health. A team led by Dr. George Uhl and Dr. Ichiro Sora of NIDA's Intramural Research Program found that cocaine could still elicit drug-seeking behavior in mice lacking the genes for either the dopamine transporter (DAT knockout mice) or the serotonin transporter (5-HTT knockout mice). These transporters had been believed to be the critical brain sites involved in the experiences of drug euphoria, reward, and ultimately addiction. Yet the two strains of knockout mice, lacking genes for the "reward" transporters, remain sensitive to the rewarding effects of cocaine. Thus, other brain mechanisms must be involved also in the brain's response to drugs or be able to compensate when the primary mechanisms are not operating fully.

"These findings suggest we should expand our search for new target sites in the brain for developing successful therapies for cocaine addiction," said Dr. Alan I. Leshner, Director of NIDA. "Many studies have pointed to dopamine, and possibly serotonin, transporters as the key reward sites associated with drug abuse and addiction. Now we have to cast the net beyond dopamine or serotonin transporters alone if we are to help cocaine addicts overcome uncontrollable craving and improve their treatment outcome."

In a study published in the June 23 Proceedings of the National Academy of Sciences, researchers set out to determine whether eliminating dopamine or serotonin transporters could affect cocaine reward--a key step in developing a model to study medications for cocaine addiction. Drug reward in the two knockout strains of mice was assessed by the "conditioned place preference" test. DAT and 5-HTT mice as well as normal, control mice are allowed on day 1 to move freely in a plexiglass chamber with two distinct compartments; one has a wire-mesh floor and the other has bedding material on its floor. The mice generally spend most of their time in the compartment with the bedding. Starting on day 2, the mice receive four conditioning sessions during which they are given, alternately, injections of saline while restricted to the bedding compartment or injections of cocaine or methylphenidate (both are stimulant drugs) while restricted to the wire-mesh compartment.

Twenty-four hours after the last conditioning session and after the acute effects of the drug wear off, the mice are allowed to enter either compartment. In this study, researchers found that DAT and 5-HTT knockout mice each showed a significant increase in preference for the wire-mesh compartment, which was the compartment associated with the drug. This finding indicates that cocaine and methylphenidate are still rewarding drugs to these mice, even though they lack the key proteins associated with the rewarding and reinforcing effects of the drugs (the dopamine or serotonin transporters).

Dr. Uhl observed that, given these results, "Cocaine appears to act on a richer array of brain sites than those previously identified as having a role in drug reward and addiction. Any medication used in cocaine treatment may also have to act on these brain sites."

The research team included investigators from NIDA's Intramural Research Program, the Intramural Research Program of the National Institute of Mental Health, and the Department of Psychiatry at the University of Wuerzburg in Germany.

NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute also carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. ...fact sheets and other information on NIDA research and activities can be found on the NIDA home page at http://www.nida.nih.gov.

[Forthesevenlakes]

Unfortunately its hard to disentangle the results of contradictory studies like this...most scientific viewpoints have an antithesis that can both be supported by certain evidence. (e.g. is alcoholism due to our genes? or is it due to someone drinking to much?) SWIM would guess a meta-analysis of all these papers would be needed to come to the best conclusion, but after studying pharmacology all day, SWIM is too tired to attempt such a feat. Anyone want to help clear this up for SWIM...is it the DAT or isnt it? The DAT could contribute to addiction in a sense that it could increase availability of DA, but isnt, in itself, required for addiction since DA could be released or DA receptors directly stimulated by cocaine in other ways. At least thats SWIM's halfassed guess. SWIM would love to know the answer though.

[Richard_smoker]

OK. First off, I want to post a working definition to the DAT protein:

The Dopamine Transporter's (DAT) specific role is clearing the neurotransmitter dopamine out of the synapse and into a glial cell or the presynaptic neuron. DAT is important for neural function because it removes excess dopamine from the synapse, effectively ending the signalling of the neurotransmitter. Cocaine blocks the action of the dopamine transporter and, to a lesser extent, other transporters. This causes an overload of dopamine in the synapse, since the neurotransmitter cannot be cleared away after it is released.

FYI, both cocaine and methylphenidate (ritalin) both inhibit the removal of several neurotransmitter-removal proteins from the synapse. This is HOW THE DRUGS WORK in the first place. In other words, coke works by blocking reuptake of dopamine and others. If the dopamine transporter is screwed-up, then OF COURSE cocaine will not even have any effect on the dopamine portion of coke's effects. These people may have elevated norepinephrine and serotonin, but NO DOPAMINE-BASED MOOD ELEVATION! So, duh! These people won't even enjoy cocaine anyway because it doesn't even do anything pleasureable to them! So, I think these 'researchers' are capitalizing on the fact that there are some 'weird' people whose DAT protein is not inhibited by coke and they're acting like this weird DAT is normal--then they are comparing this protein to REGULAR PEOPLE'S DAT'S!! In reality, the highly-addictive DAT is NORMAL (i.e. it is what most of us have). The other--fucked-up DAT--is the one that only a few people have. So, this makes you think twice when you read, "50% of cocaine addicts tested had two copies of the highly-addictive form of DAT." See what I mean!??

But they're describing the NORMAL DAT as if it's something 'weird' that leads to addiction! This is simply not true. It is a flat-out misleading lie. These are the types of glamorous news stories which justify large grants for research centers. The story is bunk. Because it is so misleading, the average person as well as the average physician will easily fall for their play-on-words. This kind of 'research' makes me SICK! I wonder how much money these bozos are going to get now!???

The major DA receptors of the striatum are D1 and D2 receptors. D2 receptors are tonically stimulated by basal levels of DA, and this tonic activity is important for normal motor behavior, whereas D1 receptors are activated by phasic release of DA and are particularly relevant in terms of DA involvement in learning and addiction. However both receptors act synergistically, and moreover, the final effect of cocaine action depends on the co-activation of several systems. For example, the induction of IEG in the striatum requires both functional D1 and NMDA receptors (Torres and Rivier, 1993) and is blunted by the selective denervation of 5-HT projections under certain conditions (Bhat and Baraban, 1993), whereas 5HT-1B receptor knockout (KO) mice exhibit reduced expression of the IEG in the striatum (Lucas et al., 1997). Cocaine also acts as a local anaesthetic causing dose-dependent inhibitions of most spontaneously active and glutamate-stimulated neurons. These inhibitions which are not dependent on DA receptors may involve direct interaction with sodium channels (Kiyatkin and Rebec, 2000), but the precise mechanism is unknown.

This last bit was just to re-inforce my original claim that the DAT-'solo' model of cocaine addiction is outdated and it is incredibly stupid and arrogant that these researchers have no faith in the public to perform their own basic research.

I found this research that is being discussed in this original posting. While the article is not a scientific study, but instead is a 'translation' of a study--for a newspaper of some sort, it is understandable that the story was sensationalized and appropriately dumbed-down not only for the masses, but I doubt that the reporter had any idea what he/she was discussing in the first place.

Here is the same news story as told by the BBC. It comes closer (I think) to telling the actual story. That is, when you take BOTH articles into consideration--because I don't believe either reporter quite got the story straight. The scientists' quotes are the same, but the amount of reporter-interference is totally different from 1 article compared to the next. Not saying either article is better. Just look at them both if you're interested in this topic. The main point is that the DAT protein is not the only factor in abuseability of coke. Many researchers believe that it's not even the main factor in abuseability. In reality, these scientists were just trying to prove a hypothesis that they formulated prior to the study--that people with certain phenotypical DAT expression were more likely to abuse cocaine. It is the way in which they presented their final conclusions that casts a dark shadow upon their final motivations--to create a sensational "breakthrough" of sorts for the purpose of becoming famous and winning shit-tons of money from unsuspecting contributors. I mean, what major corporation or pharmaceutical company wouldn't give or invest a SHITLOAD of money to a team that was on the edge of finding a CURE for cocaine addiction!?

here's the BBC report. Please note that I underlined in BLUE words that demonstrate the uncertainty of these findings, and also words that allude to the fact that DAT activity is only one of many mechanisms that MIGHT or MAY or COULD assist in the development of dependence in users:

'Gene cause' of cocaine addiction: The chances of becoming addicted to cocaine could depend on genes, the Institute of Psychiatry has found.

It identified a gene variation where cocaine would more markedly inhibit a protein that controls removal of key mood chemical dopamine in the brain.

Two copies of the variant made people 50% more likely to be cocaine abusers.

DNA of 700 cocaine abusers and 850 other people were compared for the study, published online by Proceedings of the National Academy of Sciences.

"This study is the first large scale search for a genetic variant influencing the risk of developing cocaine addiction." Dr Gerome Breen

Cocaine's action within the brain is relatively well understood. Its key effect is that it strongly inhibits the action of a protein - DAT - which controls removal of excess dopamine from the junctions between nerve cells in the brain.

This leads to nerve cells effectively being overloaded with dopamine, which is thought to contribute to the "high" associated with taking cocaine.

The latest study, funded by the Medical Research Council, identified a specific variation in the genetic code controlling production of the DAT protein.

People carrying two copies of this particular variant were 50% more likely to be cocaine dependent.

Treatment hope
Researcher Dr Gerome Breen said: "The target we investigated, DAT, is the single most important* in the development of cocaine dependence. It made sense that variation* within the gene encoding DAT would influence cocaine dependence."

Analysis showed that cocaine was likely to inhibit the DAT response more markedly in people who carried the key genetic variant.

Dr Camila Guindalini, who also worked on the study, said: "This research helps our understanding of the development of cocaine addiction. It could influence the design and use of drugs to treat cocaine abuse in the future. Although repeated exposure to cocaine will lead to compulsive use in everyone, it seems some people will become addicted to the drug more quickly than others because of a genetic difference."

Harry Shapiro, of the charity DrugScope, said: "While genetics may have a role in helping us to understand the nature of addiction, it would be wrong if this kind of research encouraged governments not to tackle the economic and social root causes of chronic, endemic drug use by instead focusing on individual pathology."

*these are presuppositions that almost certainly affected reported measurements

Notice that the more outlandish the scientists' claims, the more likely that both reports included these claims. This is what reporters are aching to submit to press... whether these claims are founded or not. Just check out the original posting and you'll find the same absolutes quoted by the same scientists.

Sorry if I have appeared to be an anus. Although I was originally mad at the post which started this thread, I am now angry at the media in general and the fools who came up with this report. I have come up 100% short on finding this so-called report and I have found access to almost every online journal known to man, still with no luck. Please, someone post the original findings because I have only located some 30 journal articles posted in 2006 which deal with cocaine and DAT. None of them appear related to these articles.

And please, I don't ever want to do this much research again in my life if no one is reading these posts. Please give me some feedback (via PM) if you actually read this post &/or found anything contained within it actually useful. Seriously, there's no point in me spending this much time if I'm just going to post to myself. I could have just masturbated and saved 2-3 hours.

-Dick "Silver Member" Smoker

Reputation Comments on this post:

Great post and good effort!

[Jatelka]

Dick, SWIJ is reading, and profoundly grateful that you did so much research (mainly because it meant she didn't have to).

It makes SWIJ really cross when scientific research is published as "fact" by biased news media. Unfortunately very few people are willing to go to the kind of effort you have to look at the original research and draw their own conclusions.

Thankyou

[klaatu]

Here's more of the same...

Strength of cocaine cravings linked to brain response
Mar 22, 2006
Reviewed by: Dr. Ankush Vidyarthi


"It really shows that the addicted person is ill-equipped to cope because the brain is now wired to make them crave drugs more and get less satisfaction out of the drug or other life events that may be rewarding, and this study found biological changes that would explain these behavioral changes,"


By University of Texas Southwestern Medical School, Rats that have a strong craving for cocaine have a different biochemical response to the drug than their less-addicted counterparts, researchers at UT Southwestern Medical Center have found.

The difference lies in the pleasure-seeking area of the brain, according to a study available online and appearing in a future issue of the journal Neuropsychopharmacology.

"This work shows that there are profound alterations in the brain mechanisms that regulate motivated behavior with addiction," said Dr. David Self, associate professor of psychiatry at UT Southwestern and senior author of the paper.

"It really shows that the addicted person is ill-equipped to cope because the brain is now wired to make them crave drugs more and get less satisfaction out of the drug or other life events that may be rewarding, and this study found biological changes that would explain these behavioral changes," said Dr. Self.

The researchers looked at dopamine receptors — molecules on cell surfaces that are activated when dopamine or other molecules bind to them. They focused on two types of receptors called D1 and D2.

Molecules that activate D1 are believed to decrease the craving response, while D2 activators are believed to increase it. Both of the receptors bind to the neurotransmitter dopamine in a part of the brain called the mesolimbic dopamine system.

In the study, rats had tubes surgically implanted that fed into their bloodstream, through which they could give themselves cocaine injections by pressing a lever. Some rats voluntarily gave themselves higher doses of cocaine than others did, an indication that they were more addicted to the cocaine.

The rats then went through three weeks of cocaine withdrawal, during which time they ceased to press the lever. At the late stages of withdrawal, a drug that specifically activated the D2 receptor was given to see if it would prompt the rats to press the lever again in search of cocaine. In another experiment, the rats were given a small dose of cocaine and a drug that activated the D1 receptor to see if the drug would block them from seeking more cocaine.

The strongly addicted rats responded more aggressively to the craving-enhancing D2 activator than the less-addicted rats did, and were not as strongly deterred by the D1 activator.

"It's as if the cocaine-addicted animal is less easily satisfied and more easily induced to seek drugs due to alterations in these receptors," Dr. Self said.

Before the researchers administered cocaine, the rats were tested to see how much they moved around when given D1 or D2 activator drugs. Before getting the cocaine, their responses to each drug were the same. After being trained to take the cocaine, the strongly addicted rats were much more sensitive to the D2 activator but less sensitive to the D1 activator. These tests showed that the difference in sensitivity developed during the addiction process, rather than being already present in the animals from the beginning.

The researchers don't know, however, whether the responses in the rats they studied were due to changes in the numbers of the receptors or to the biochemical actions of the receptors already present. Future research may help clarify those different scenarios, Dr. Self said.

Understanding how receptors control cravings may be applicable to humans, although addiction is a complicated mix of brain biochemistry and learned responses to environmental cues, as well as stress, Dr. Self said.

"If people do become addicted and say they want to quit, their brain system for inhibiting craving is weaker. We want to try to strengthen those systems that help them inhibit their craving," he said.

The lead author in the study was Scott Edwards, a neuroscience graduate student at UT Southwestern. Other UT Southwestern researchers involved in the study were Kimberly Whisler, a research associate in psychiatry, Dwain Fuller, faculty associate in psychiatry, and Dr. Paul Orsulak, professor of psychiatry and pathology.

- The difference lies in the pleasure-seeking area of the brain, according to a study available online and appearing in a future issue of the journal Neuropsychopharmacology.

www.utsouthwestern.edu

[Richard_smoker]

Hey, maybe I'm the one who's wrong... that article is pretty convincing. I didn't even think of the fact that D1 and D2 were so strongly linked to repetition that it might not even matter what the ENTIRE story was about what is going on in the brain... sorry

Here's an article from 1998 (I think) that shows how some other pathways are involved as well... maybe a few years after they come out with a dopamine addiction pill, the drug co's can come out with a different, more-improved drug that hits serotonin, etc. as well!

Dopamine Theory of Cocaine Addiciton Challenged by Research

By Richard Karel, Psychiatric News, 1998
Two new studies in the journals Nature Neuroscience and Nature pose a potentially revolutionary challenge to the primacy of the dopamine hypothesis of cocaine addiction.
For more than a decade, research on cocaine has converged around the hypothesis that the drug's reinforcing effects are inextricably tied to its capacity to bind directly to the dopamine transporter (DAT), thus blocking dopamine reuptake and raising extracellular concentrations of released dopamine. High levels of extracellular dopamine are one of the measurable effects of cocaine administration in laboratory animals and have been seen as the key to the drug's stimulating and reinforcing properties.
Scientists had long known that cocaine has a greater affinity for the serotonin transporter than the DAT, but they had assumed that serotonin merely modulated the primary reinforcing effects of extracellular dopamine. The new research, however, suggests that the dopamine system, while relevant to cocaine's reinforcing effects, is but part of a more complex series of neuro-cellular systems in which serotonin plays a far more significant role than previously supposed.
If these findings are replicated, they will force a reappraisal of the dopamine hypothesis and undoubtedly trigger a scramble for new approaches to the study of drug addiction.
The most startling of the two studies, titled "Cocaine self-administration in dopamine-transporter knockout mice," was published in the June 1998 Nature Neuroscience. Principal investigator Marc Caron, Ph.D., a neurobiologist at Duke University Medical Center in Durham, N.C., and lead researcher Beatriz Rocha, M.D., Ph.D., an assistant professor at the University of North Texas Health Science Center in Fort Worth, and colleagues, employed a genetic engineering technique known as "knockout" in which mice are bred to lack a specific neuroanatomical structure (in this case the dopamine transporter), believed responsible for a given behavior or symptom of disease. The hypothesis, quite simply, was that if the DAT was responsible for cocaine's reinforcing effects, then mice without the DAT would not self-administer a cocaine solution when given the chance. But that wasn't what happened.
Instead, the mice repeatedly self-administered cocaine, just like mice with normal DAT systems.
"It is remarkable that the DAT-knockout mice, which are already under the influence of the primary pharmacological action of cocaine, elevated dopamine, still self-administer the drug," the authors observe. They conclude that "the molecular targets for cocaine and the pathways that underlie the acquisition and maintenance of the drug-taking behavior in DAT-knockout mice must involve neuronal pathways other than the dopamine system."
The researchers speculate that the serotonin transporter plays a critical role in cocaine's reinforcing effects.
One scientist who has been instrumental in advancing the dopamine hypothesis of addictive drug reinforcement is George Koob, Ph.D., a professor of neuropharmacology at the Scripps Research Institute in La Jolla, Calif.
"I don't know how to interpret the knockout of the transporter," Koob told Psychiatric News. "The theory is that is the way cocaine works, but maybe cocaine does other things to the dopamine neuron."
There may be "compensatory changes occurring in other transmitter systems," he continued. "People have hypothesized there can be multiple, parallel reward systems as opposed to an in-series dopamine reward circuit. If you're going to look for changes that occur in addicts, then you may have to look at these other pathways as well."
The DAT paper complements a study in the May 14 issue of Nature on how cocaine affects mice engineered to lack one of the 14 serotonin receptors. In that study ("Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor"), Rocha and principal investigator Rene Hen, Ph.D., an associate professor of pharmacology in psychiatry at the Center for Neurobiology and Behavior at Columbia University in New York, and colleagues, found that the serotonin receptor-knockout mice were more sensitive to cocaine's reinforcing effects than normal mice. This finding appears to contradict earlier research, which found that stimulating serotonin receptors mimicked some effects of cocaine while blocking those receptors lessened the effects of cocaine.
The authors speculate that the serotonin receptor-deficient mice developed some sort of compensatory mechanism that sensitized them to cocaine. Another possibility is that prior studies of the interaction of cocaine and serotonin systems were compromised by the lack of receptor specificity of some of the drugs used in the experiments, said Francis White, Ph.D., of the department of cellular and molecular pharmacology at Chicago Medical School in a commentary accompanying the Nature article.
George Uhl, M.D., Ph.D., is director of the molecular neurobiology branch at the National Institute on Drug Abuse, one of the first laboratories to clone the dopamine receptor. Earlier work on DAT-knockout mice found that the mice had a much diminished locomotor response to cocaine. But those findings, said Uhl, were over-generalized to suggest that the mice were invulnerable to cocaine's reinforcing effects.
The new research suggests that "dopamine still could participate in the drug's rewarding effects in normal animals and humans, but that it's not the only possible mechanism for cocaine reward," Uhl commented. "And this is somewhat surprising considering" prior research. Earlier work with mice engineered to have extra DAT found that the animals were extra-sensitive to cocaine's reinforcing effects, he noted. So while the prior evidence is not disproved, the new findings "will require us to rethink these classical paradigms."
Although the use of genetically engineered mice is an invaluable tool for researchers trying to elucidate the role of specific brain systems, it is possible and indeed likely that brain systems work differently in normal animals, Uhl observed. Generalizing from animals to humans is even more tentative, due to the complexity of human behavior, he added.

[Richard_smoker]

Here's more evidence that dopamine is not THE central player... anyone else have thoughts on glutamate??? after all, glutamate is the opposing player to GABA. Glutamate turns "ON" and GABA turns "OFF" neuron firing.

Phenotype Offers New Perception on Cocaine

Researchers say glutamate is more essential to addiction than dopamine By Tom Hollon

In cocaine research, dopamine and glutamate make a brilliant star and supporting player, respectively. One takes center stage, the anointed crowd-pleaser; the other, though a leading actor in other productions, is so overshadowed that admiration of its performance is relegated to an acquired taste. A quick PubMed search recently disclosed their perceived importance: 3,628 abstracts on cocaine and dopamine, 178 for cocaine and glutamate.

Now, however, perceptions may shift - not that dopamine descends from the firmament, but that glutamate will sparkle as brightly. Recent knockout mouse evidence1 from researchers led by François Conquet, CEO of Addex Pharmaceuticals in Geneva, Switzerland, reveals that glutamate's role in cocaine dependence is even more central than dopamine's.

The case for dopamine's centrality remains airtight. Cocaine binds the dopamine transporter, blocking reuptake of dopamine into presynaptic neurons. Blockade increases dopamine concentration in synapses, an event responsible for cocaine's pleasurable effects and suggested as key to developing drug dependence. But although loss of the transporter and dopamine receptors in knockout mice may alter behavior toward cocaine, always the drug remains addictive. When the dopamine transporter is lost, for instance, mice may still become cocaine dependent through cocaine's ability to bind the serotonin transporter. This is not necessarily surprising, observes Peter Kalivas, of the Medical University of South Carolina in Charleston, who is a leading investigator of the glutamate-cocaine relationship. "The ability of an organism to predict rewarding stimuli in the environment is absolutely critical to survival," says Kalivas, "so there probably is some redundancy."

Contrast this redundancy to what Conquet finds when metabotropic glutamate receptor mGluR5 disappears: Without mGluR5, mice turn up noses and whiskers to cocaine, even though their dopaminergic systems respond to cocaine as usual. "These are the first knockout mice completely unresponsive to this powerfully addictive drug," says Conquet, who engineered the knockout mice when he was at GlaxoSmithKline in Lausanne, Switzerland. From this phenotype emerges a new picture of dopamine and glutamate: Sustaining cocaine-seeking behavior requires both neurotransmitters, while only glutamate is indispensable for cocaine dependence.


The Consolation Prize

Glutamate, the main excitatory neurotransmitter, is associated with learning and memory. Its receptors divide into ionotropic and metabotropic forms important to this function. "Learning occurs in part from changes in both ionotropic and metabotropic signals," Kalivas explains. "You adjust both in order to change the way cells communicate." Ionotropic receptors are also called ligandgated ion channels. Ligand binding opens the channel so ions can pass through the cell membrane. Generally these are ion channels first, receptors second, controlling very quick changes in membrane current. In comparison, metabotropic glutamate receptors bring slower changes; largely they modulate signals from other neurotransmitters, acting through second messenger systems. They belong to the seven-transmembrane, G-protein linked superfamily of receptors. Conquet studies metabotropic receptors mGluR1 and mGluR5, which act through the phospholipase C signaling pathway.

Conquet's discovery of mGluR5's role in cocaine addiction originates in his second-place finish in a race to make mGluR5 knockout mice. Conquet was at the time head of Glaxo's experimental pathology unit, where his job was to make knockout mice deficient in various neuronal receptors. He lost to John Roder, of the Hospital for Sick Children, in Toronto. By showing that mGluR5 mutant mice perform poorly in the Morris water maze test and in fear-related learning, Roder implicated mGluR5 in spatial learning and memory.2 Roder's experiments suggest that mGluR5 is involved in long-term potentiation (LTP) within the hippocampus. Scooped, Conquet had to ask himself if Roder's description of the phenotype was complete. A possibility Roder might have missed, Conquet decided, was how the mice would react to cocaine.

The possibility of a connection between mGluR5 and cocaine appealed to Conquet's sense of drug dependence as a form of learned behavior. He knew that cocaine increases glutamate concentration in the nucleus accumbens, a brain region associated with cocaine dependence and stimulation of locomotor activity, and the location for the natural reward circuitry for food, water, mating and maternal behavior. Kalivas and his associates have demonstrated that mGluR5 receptors are down regulated following chronic cocaine administration.3

Conquet turned for help to his colleague Christian Chiamulera, who works on psychiatric drugs in a Glaxo laboratory in Verona, Italy. Willing to take a flyer on a wild idea, but wanting to avoid weeks of work with nothing to show for it, Chiamulera suggested a quick-and-dirty observation of cocaine as a psychostimulant: Inject cocaine into the bellies of the knockouts, then look for hyperactivity.

When Conquet watched the first injections, immediately he worried something was wrong. Instead of frenzied exploration of their surroundings, the mGluR5 knockouts lolled about as if nothing had happened. They verified in fact that the mice had received walloping doses. To their excitement, wild type mice on cocaine behaved as expected - no sleepwalkers or indolent beachcombers here. These creatures were ready to jitterbug 'til dawn at Mardi Gras. Conquet and Chiamulera were ready to join them. Chiamulera would now follow up with more elaborate experiments. For a test that approximates cocaine addiction in humans, Conquet brought in Mark Epping-Jordan, another Glaxo scientist, to do cocaine self-administration experiments.
Chiamulera confirmed his initial results. Wild type mice responded to cocaine in a dose-dependent manner: The higher the dose, the more hyperactive they became. Knockouts remained unperturbed regardless of dose. Abolishing mGluR5 abolishes cocaine-induced hyperactivity.
Epping-Jordan began the self-administration experiments by first training knockout and wild type mice to press a lever in order to get food. Both groups learned lever pressing equally well. Then he substituted intravenous cocaine for food and watched what happened. Wild type mice responded enthusiastically to the new menu, and would press for cocaine a dozen or more times an hour. MGluR5 mutants ignored cocaine at every dose; within a few sessions they would learn levers no longer produced food and stop pressing.
It was possible that the connection between cocaine dependence and mGluR5 was indirect, that loss of mGluR5 during development altered molecules even closer to control of dependence. Conquet's group examined the issue by asking if 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, reduced cocaine self-administration in normal mice. It did—In dose-dependent fashion, MPEP decreased demand for cocaine by up to 50%. The link, then, is direct and essential. "Somehow, glutamate transmission at mGluR5 is critical for the animal to recognize the rewarding effects of cocaine," says Kalivas. "The surprising thing is that it must be a secondary effect, because cocaine does not act directly on glutamate transmission. There is no binding by cocaine directly to any protein that has to do with glutamate transmission."


Leaving Natural Reward Along

Loss of mGluR5 apparently leaves the dopaminergic system intact. Using microdialysis to measure dopamine in freely moving mice, the researchers found dopamine concentrations in the nucleus accumbens were the same for mutant and normal mice, with or without cocaine. Levels of D1 and D2-class dopamine receptors and dopamine transporters were also normal. Most striking is that reward systems strongly influenced by dopamine - nourishment, mating, and nursing - were also unaffected by loss of mGluR5. Conquet emphasizes that no other knockout has behaved this way: "This is the first time a mammal has been found insensitive to cocaine while its other reward-based systems remain normal."
He continues, "Dopamine receptor knockouts fail to curb cocaine dependence because mGluR5 is still working. They just affect general dopaminergic activity," and with considerable "collateral damage". Experiments with dopamine receptor agonists also indicate that dopamine does not lie at the center of cocaine dependence: "People have shown that you can never induce dependence from scratch with dopamine agonists. But you can maintain the process with these compounds once dependence is ongoing, probably after mGluR5 has turned the system on."
Kalivas now distinguishes dopamine and glutamate by their short and long term effects. "The acute rewarding properties that keep people coming back to the drug are mediated by dopamine," he says. "The 'Once an addict, always an addict' kinds of folklore that really make an addict are probably long-term changes in glutamate transmission." In retrospect, this isn't surprising: "All of neuroscience has been pointing to glutamate transmission as the critical player in the brain's ability to adapt to the environment." Cocaine addiction is one such adaptation.


From Scientist to Entrepreneur

Conquet founded Addex only a few weeks ago, departing Glaxo for better opportunities to continue his work. Following Glaxo's merger with SmithKline, drugs against cocaine addiction seemed better markets for smaller companies. Glaxo's larger size demands larger markets if the pharma giant is to sustain itself. For a small firm like Addex, a new mGluR5 antagonist could be quite profitable. Why develop a new drug when MPEP exists? Because MPEP dissolves very poorly and barely crosses the blood-brain barrier, Conquet explains. Conquet does not know if mGluR5 plays a role with ethanol and nicotine addiction. Self-administration experiments have not been done. Partly he hasn't had time, since he's busy starting Addex. Partly the mice haven't had time, since other drugs of abuse, especially alcohol, require longer training periods. Whether mGluR5 influences other so-called addictions, is a question left for the distant future.

If Addex does find a good mGluR5 antagonist, therapeutic possibilities may extend well beyond helping snorters and crackheads stay clean. Glutamate may be implicated in numerous psychiatric disorders, according to Kalivas. mGluR5 inhibitors have been suggested as possible treatments for Alzheimer Disease, Parkinsonian akinesia, muscle rigidity, stroke, anxiety, and inflammatory pain. But as always, Kalivas reminds, once a good drug candidate is in hand, only running the clinical experiments will tell for sure.
Tom Hollon (thollon@starpower.net) is a freelance writer in Rockville, Md.

References
1. C. Chiamulera et al., "Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice," Nature Neuroscience, 4:873-4, September 2001.
2. Z. Jia et al, "Gene targeting reveals a role for the glutamate receptors mGluR5 and GluR2 in learning and memory," Physiology and Behavior, 73:793-802, August 2001.
3. C.J. Swanson et al., "Repeated cocaine administration attenuates group I metabotropic glutamate receptor-mediated glutamate release and behavioral activation: a potential role for Homer," Journal of Neuroscience, 21:9043-52, Nov. 15, 2001.

[Richard_smoker]

This also seems pretty on-target as far as hypotheses (from multi-field extrapolation) go.

Cocaine, especially crack, can hook some users on the first try; anyone can become addicted after repeated use. In scientific studies, rats or monkeys are hooked up to an intravenous source of the drug being studied. If the drug is heroin, the animals will self-administer it indefinitely, but they do still sleep and eat. Rats or monkeys who can self-administer cocaine, however, will do virtually nothing else. They even stop eating and sleeping. They continue to push their drug-delivery lever for as long as they are physically capable of doing so. Within weeks, if not days, they lose a substantial portion of their body weight, up to 40%. Within a month, they are dead.

Cocaine-addicted rats become excited when they simply see the lever that selects cocaine. It's called an addiction "cue." Human cocaine addicts have cues too. They may have a racing heartbeat when they see the things that go with taking cocaine, like large amounts of cash, straws, or crack pipes. Even recovered cocaine addicts - people who haven't used in years -- will often have intense cravings when they pass by a place where they used cocaine or they hear someone talk about using.

With respect to cocaine addiction, scientists have recently isolated a brain protein called delta-FosB (pronounced "fawz-bee") that builds up in a cocaine abusers' brain and changes its functioning, maybe forever. The protein isn't produced in the brain until someone has used cocaine for a while. Once the buildup begins, the need for the drug becomes overpowering and the user's behavior becomes increasingly compulsive. ``It's almost like a molecular switch,'' said Eric Nestler, who led the research into delta-FosB. ``Once it's flipped on, it stays on, and doesn't go away easily.''

After the drug-fueled high comes the crash. The crash involves anxiety, depression, irritability, extreme fatigue and paranoia. Physical health may deteriorate. An intense craving for more cocaine develops. Stereotyped compulsive and repetitive patterned behavior may occur, meaning that the person will repeat certain odd physical movements over and over. Many addicts experience tactile hallucinations of insects crawling underneath the skin ("formication.") Severe depressive conditions, agitated delirium and a syndrome known as toxic paranoid psychosis may follow.
A Protein Key To Cocaine Addiction

Scientists have found a key to cocaine addiction that may point toward more effective treatments. The key is a protein that functions almost as a "switch" that turns on the uncontrollable cravings of drug addicts.
The protein of interest is called delta-FosB, Researchers have known for some time that prolonged use of cocaine increases the production of this protein in the nucleus accumbens, a region of the brain important for the perception of pleasure. The study showed prolonged use of cocaine, amphetamines, morphine, nicotine and PCP triggers the production of delta-FosB. Delta-FosB then activates a gene that produces components of various neurotransmitters, such as dopamine and serotonin.
The lead researcher on the study, Eric Nestler, says, "By discovering a role for delta-FosB, we can now try to intervene either at the level of delta-FosB - or of any of its relevant target genes - to perhaps arrest or reverse the addiction process."

www.applesforhealth.com/cocaineadd1.html
The Molecular Fingerprint of Cocaine Addiction

One recent study identified more than 400 human genes that are affected by long-term cocaine abuse. This discovery represents the first molecular profile, or fingerprint, for human drug addiction and ultimately could lead to new treatments for addiction. The genes in question seem to be been either turned "on" or "off" due to long-term cocaine use; they are "disregulated" by the drug.

Scientists expect to find more cocaine-disregulated genes, and hope to study which genes are not disregulated by the drug and why. The author of the study, Dr. Hemby , says that it now appears that genes form the biological underpinnings for addiction. Understanding the mechanisms at the gene level could allow the development of addiction treatments. However, Dr. Hemby adds, "It isn't reasonable to believe that we can cure cocaine addicts," he says. "Any therapeutic approach should instead be designed to prevent relapse."

www.emory.edu/WHSC/YERKES/NEWSROOM/hemby.html

The Possible Role of Serotonin

Two 1998 studies suggest that the popular hypothesis for how cocaine works in the brain is incomplete. For 30 years, researchers have theorized that dopamine, a brain chemical involved in sensations of reward and pleasure, is required for cocaine addiction. These studies used "knockout mice" - mice with a specific gene removed before birth - to show that the neurotransmitter serotonin may also play a large role in cocaine addiction.
Without the "dopamine transporter" gene, the knockout mice should not have wanted cocaine and should not have self-administered it. The flood of dopamine in their brains caused by the lack of a dopamine transporter should have made them feel "coked up" without the cocaine. But the animals did continue to give themselves cocaine anyway, leading the researchers to the serotonin transmission hypothesis.
A follow-up study used mice with a serotonin receptor called 1B "knocked out." These mice also rapidly learned to inject themselves repeatedly with cocaine. Their brains seemed to be compensating for the absence of the serotonin 1B receptor. It appeared after further study that the mice had high levels of the protein delta-FosB, which in normal mice is only found in high amounts after the animal has been given chronic doses of cocaine. In other words, these knockout mice were born as if addicted to cocaine.

http://www.wellesley.edu/Chemistry/Chem101/addiction/sci-cocaine-addiction.html
http://www.archives.nytimes.com

Cocaine Abuse: The Self Medication Hypothesis
Two 1998 studies suggest that the popular hypothesis for how cocaine works in the brain is incomplete. For 30 years, researchers have theorized that dopamine, a brain chemical involved in sensations of reward and pleasure, is required for cocaine addiction.
These studies used "knockout mice" - mice with a specific gene removed before birth - to show that the neurotransmitter serotonin may also play a large role in cocaine addiction. Without the "dopamine transporter" gene, the knockout mice should not have wanted cocaine and should not have self-administered it. The flood of dopamine in their brains caused by the lack of a dopamine transporter should have made them feel "coked up" without the cocaine. But the animals did continue to give themselves cocaine anyway, leading the researchers to the serotonin transmission hypothesis.

A follow-up study used mice with a serotonin receptor called 1B "knocked out." These mice also rapidly learned to inject themselves repeatedly with cocaine. Their brains seemed to be compensating for the absence of the serotonin 1B receptor. It appeared after further study that the mice had high levels of the protein delta-FosB, which in normal mice is only found in high amounts after the animal has been given chronic doses of cocaine.In other words, these knockout mice were born as if addicted to cocaine.

http://www.wellesley.edu/Chemistry/C...addiction.html
http://www.archives.nytimes.com

Cocaine Abuse: The Self Medication Hypothesis

Various researchers have examined the idea that some drug addicts and alcoholics become addicted in a subconscious effort to "treat" their psychiatric illnesses. Psychiatric disorders, particularly the disorders having to do with mood, seem to increase a person's risk of developing stimulant abuse. Psychoactive drugs interact with the individual's own psychiatric disturbances and painful emotional states. These people become addicted to cocaine and suffer the same devastating health damage as other addicts.
If the underlying psychiatric illness is diagnosed, it can be treated with appropriate medications. When the psychiatric illness is under control, the addiction can often be resolved. Even though depression is readily treatable with highly effective pharmaceutical drugs, some individuals with major depression choose to abuse cocaine to "self-medicate." Those individuals may experience some relief of fatigue and low mood. Others have increased feelings of self esteem, assertiveness, and frustration tolerance, among other symptoms. Another group of people who often select cocaine as their drug of abuse are those with attention-deficit hyperactivity disorder (ADHD,) who experience less impulsive or hyperactive behavior. Individuals with ADHD seem to have a "paradoxical" (opposite to the usual) response to cocaine that allows them to feel more calm than they otherwise feel.

It also appears that some with cyclical mood disorders (bipolar or manic depressive disorder, cyclothymic disorders) may select stimulants like cocaine over other substances of abuse.
http://www.druglibrary.org/schaffer/cocaine/addhyp.htm#table

[Lunar Loops]

Just to add to this old thread, I found this article on thetyee.ca and thought it relevant (not to mention a good read....damn, I've mentioned it now):
Myth of an 'Addict Gene'


Why it's dangerous to assume addiction is inherited.
Why it's dangerous to assume addiction is inherited.

By Jeffrey Helm Published: July 28, 2006

Ten years ago science was said to be homing in on the "alcoholism gene." Could a gene-based cure for addiction be far away?
Well, yes it could. It's very far away, if even possible at all. Researchers now have identified over a thousand genes linked to alcoholism. The genetics of alcoholism mirrors what has become increasingly apparent to geneticists: life is complicated. The way you act or the quality of your health is likely influenced by many genes interacting with each other along with various environmental factors. The concept that a small number of genes are responsible for disease or behaviour is obsolete.
What that means, in the case of alcoholics or drug addicts, is that even if your parents were addicted, it's unlikely that their genes are the deciding factor that will make you an addict.
But many people still hold the outdated, simplified view that key genes "cause" most disease and addiction. And what we don't understand can hurt us. Biomedical ethicists warn that if public policy doesn't catch up with scientific knowledge, then people at risk of addiction will be stigmatized even more than they are now. Life insurance and employment could be denied and genetic screening could stop people 'at risk' of addiction before they are even born.
Life's nose pokes
Genes are information. How that information is expressed within your body depends on diet, stress and even social interactions, researchers say.
"There are almost no examples where genetics works in exclusion of environment," said Dr. Elizabeth Simpson, a geneticist and professor in the department of medical genetics at UBC. In fact, environmental factors "are important not just in the disease itself, but the course of the disease, the severity of the disease and whether it is actually a significant event in a person's life or not," Simpson told The Tyee.
Recent research has found a way to look at the influence of environmental factors on drug use in lab rats.
Two lines of rats were bred to have different levels of reaction to apomorphine, a derivative of morphine. One breed doesn't react to the drug very much (Weak Drug Response rats), and the other has a strong reaction (Strong Drug Response rats). When cocaine or alcohol was made freely available to the rats, WDR rats drank more alcohol and used more cocaine than SDR rats.
The scientists then looked at the effect of a stressful life experience on drug usage in the rats; they were put into a new cage and poked in the nose.
After the stressful nose poke, SDR rats increased their consumption of alcohol over a prolonged period, while the WDR rats only increased their drinking for a short time. The SDR rats also used more cocaine after the stressful experience than WDR rats.
The genetics of the rats predicted an outcome that was reversed with one nose-poke. Rats that seemed genetically predisposed to drug use before the stressful event ended up using less afterwards, and rats that used less before ended up using more drugs after. If drug use can change so completely with only one event in a rat's life, it's not hard to imagine how chaotic, stressful lives might lead to humans using more drugs or alcohol.
Tangle of genetic influences
"Multiple genes with small effect is really a scientific discovery of the last ten years, which is very challenging in the way we think about genetics, and it's not the point of view the public knows right now," says Dr. Elizabeth Simpson.
There are thousands of genes that have been linked to addiction, most of them relating to how drugs of abuse work in the brain. Other groups of genes have been linked to traits that make up an "addictive personality," like impulsivity, risk-taking and novelty seeking.
Genetics cannot predict whether someone will develop an addiction; at most genetics will identify risk factors. But genetics can determine what therapies have the greatest chance of working.
"The knowledge of the genetic basis of the disease opens up possibility of treatment, and prevents lots of treatments that don't work," says Dr. Simpson.
There are many different ways that addiction can get wired into the brain. Genetic analysis of a person's genes can pinpoint what is most likely to be contributing to that person's addiction problem. For example, genes for processing an addictive drug could be normal while there are deviations in genes involved in feelings of self-esteem. That would indicate that therapies focusing just on blocking the effect of the drug would not be as effective as therapies focusing on self-esteem.
Using genetic information to get a more holistic look at a person's health is where medicine is heading. But before that becomes possible, the cost of a complete analysis of a person's genes needs to come down in both price and manpower.
Ten years ago, scientists were just starting to figure out how to analyze the genes (or genome) of a person, the Human Genome Project was pumping hundreds of millions of dollars into the effort. Ten years from now it is likely to cost a few hundred dollars and a couple days of work.
"Your baby is born, and should you want it, you have their genome sequenced for a thousand dollars," predicts Dr. Simpson. "What's hard about that thousand dollar genome is, what does that information actually mean?"
The gene screen
Addiction cannot be predicted through genetics alone, but researchers are still trying to identify people at risk of developing addiction. This means that genetic tests for risk factors in addiction are likely to appear somewhere down the road. The danger in such a test is that the genetic information will be viewed as a reliable predictor of a person's lifestyle and capabilities, when it isn't. Misinterpretation of genetic information resulting in discrimination is already happening.
In 2002, the Burlington Northern Santa Fe Railway Company in the United States secretly tested its employees for a genetic variation thought to be responsible for carpal tunnel syndrome. The variation did not accurately predict carpal tunnel syndrome and the company paid out $2.2 million in a settlement.
In 2003, a young German woman was denied employment as a teacher because of a family history of Huntington's disease. The examining physician said that the woman was fit to do the job but there was a 'higher risk' of future absenteeism. If the woman did have Huntington's disease, which was not known, then the symptoms would only be likely to gradually appear after 20 to 30 years of teaching.
In 2004, a research team studying genetic discrimination in Canada published a report in the Lancet stating that people in Canada have also been denied life insurance because of a family history of Huntington's disease. Positive genetic diagnosis of the disease has also caused problems at work for people when employers knew the results of the genetic testing. These cases have lead bioethicists to question the practices of the insurance industry and call for a halt in the use genetic information for both employers and insurance companies.
Even though Huntington's is one of the rare genetic diseases that is based solely on genetics and not environmental factors, it illustrates what could happen to other conditions, like addiction, if they are viewed as being strongly genetically based.
Currently in Canada there are no laws prohibiting genetic discrimination. Insurance companies are free to demand genetic testing and use the results to deny coverage.

'Good' and 'bad' genes

With genetic testing also comes the ability to screen out undesirable genetic traits from the population.
Dr. Tom Koch, a bioethicist and professor at both UBC and SFU, is concerned that if a genetic test for addiction were developed, children with genetic risk factors for addiction would be weeded out because only fetuses or embryos free of "deviant" genes would be brought to term.
Dr. Koch proposed that screening out unwanted genes is essentially the same as deciding that the world is better off without those genes. So is the world better off without people with a biological susceptibility towards becoming addicted?
If the answer is yes, Dr. Koch points out that people like Dylan Thomas, William S Burroughs, and Miles Davis might not have existed and brought their art and music into the world. All were artists who struggled with substance abuse.
The Assisted Human Reproduction Act, signed in 2004, is the legislation that monitors genetic screening of embryos and fetuses. The law created a government agency to monitor and regulate the use of all genetic reproduction technology in Canada. Even though the legislation has been praised for being very comprehensive and socially accountable, disability rights proponents have called for tighter regulation of genetic screening.
The concerns of disability rights supporters are the same as those outlined by Dr. Koch: that weeding out "deviant" genes would also weed out and devalue the contributions of valuable people that have a disability, or a greater risk of developing an addiction.
By labeling people as "at risk" of addiction based solely on genetics, Dr. Koch says, "you would stigmatize those that were allowed to be born, on the basis of genetics that is not their fault, and which may or may not be problematic in the way they live."