What Part Of The Brain Controls Addiction

Our flourishing knowledge of the encephalon is in large part the product of inquiry on addiction. Identifying what happens in the encephalon when a drug is inhaled, injected, or eaten, why information technology leads to compulsive drug seeking, and learning how to disrupt that process has seemed like the terminal all-time hope for a permanent fix for habit. Which is why, co-ordinate to Alan Leshner, director of the National Found on Drug Abuse (NIDA), researchers know more than about drugs in the encephalon than they know about annihilation else in the brain.

Among the revelations: addiction is now seen to be a encephalon disease triggered by frequent utilize of drugs that change the biochemistry and anatomy of neurons and alter the style they piece of work. Scientists have developed a basic model of habit that presents these changes equally the desperate attempt of the brain to carry on business-as-usual—to make neurons less responsive to the drugs and so restore homeostasis—while nether extreme chemical siege.

But the adaptations the drugs force on the brain can be long term or fifty-fifty permanent. With sustained drug use, the brain adapts to this saturation battery, and giving upwards drugs leaves it bereft and demanding a return to the new homeostasis. Thus, even the brains of people who take quit using drugs and urgently wish to stay clean remain vulnerable to relapse. Deprived addicts are no longer seeking to go high, they just desire to feel normal.

Genetic factors, ecology factors, and—well-nigh of import—the intricate and still mysterious interaction of the two are assumed to be fundamental to the addiction process. Merely a great many critical details are emerging from studies of events in the brain.

The common pathway

The most compelling revelation near addiction and the brain may even deserve that tattered encomium "breakthrough." The discovery that startled the scientists? Although each drug employs it in a somewhat dissimilar way, addictions center around alterations in a single pathway in the brain: the "reward" excursion whose chief centers of action lie in the ancient part of the brain known as the limbic system.

This pathway is involved in drug addictions of all kinds—not only addiction to illegal drugs such as heroin and cocaine, only also addiction to booze, tobacco, and even caffeine. Marijuana appears to use this pathway too. And peradventure—a big mayhap because addiction experts are divided on this point—the pathway also figures in "addictions" that exercise not involve drugs, for example, the compulsive and subversive pursuit of eating, exercise, gambling, or sexual practice.

The addiction pathway is the brain organization that governs motivated beliefs. When the pathway was get-go discovered, almost a half-century ago, people called it the pleasure center. Scientists at present telephone call it the brain reward region and take confirmed its role every bit the addiction pathway in countless beast studies (by and large with rats and mice) and many brain-imaging studies of human addicts.

The pathway is subconscious deep within the brain (see illustration page 514). It begins at the ventral tegmental expanse in the midbrain, which sits on tiptop of the brainstem. In evolutionary terms, this region is very old; information technology began with the vertebrates, which appeared 500 million years or and then ago. The pathway extends to the nucleus accumbens, toward the forepart of the brain. This surface area is a traffic hub for signals to and from the addiction pathway and other parts of the brain. The nucleus accumbens is centrally located at the intersection of the stria-turn (where motility is begun and controlled) and the limbic system.

The limbic organisation is a collection of primeval brain structures that form a ring effectually the brain stem. Amidst those structures are the hippocampus, the brain'due south center of learning and memory, and the amygdala, the postulated site of, among other things, our emotional responses to experience. These are aboriginal centers of cerebral processing, only they still guide our behavior, sometimes to our woe. They long antedate the neocortex, where (amongst other tasks) rational idea processes are believed to take place. The limbic system is likewise closely connected to the hypothalamus, a tiny surface area in the center of the brain that controls many hormones, and with them, hunger, thirst, and sexual desire.

In brusque, the addiction pathway has been effectually a lot longer than humanity and is situated within piece of cake reach of ancient brain centers that control many basic functions, well-nigh of them unconscious, that people share with other animals.

Drugs and the dopamine path

Chemicals called neurotransmitters laissez passer messages from 1 neuron to another across the gaps (synapses) that divide them. Dopamine is among the nearly common of the more than 100 neurotransmitters that have been identified so far, although information technology is made in perchance fewer than 100,000 nerve cells out of the brain's 100 billion. Dopamine is too the chief neuro-transmitter in the brain advantage pathway. From cell bodies in the ventral tegmentum, electric commands get out, leaping along the cells' cablelike axons to their terminals in the nucleus accumbens, where dopamine is ejaculated into the synapses.

Addictions middle around alterations in the brain'southward mesolimbic dopamine pathway, also known every bit the reward circuit, which begins in the ventral tegmental area (VTA) above the encephalon stem. Jail cell bodies of dopamine neurons ascend in the VTA, and their axons extend to the nucleus accumbens. This centrally located hub connects with many other brain structures, such equally the limbic system (the so-called emotional brain, in evolutionary terms very sometime). Some dopamine fibers also project to a much newer structure, the prefontal cortex, which is involved in cognitive tasks such as retentiveness, planning, attention, and social behavior. Analogy courtesy of the National Establish on Drug Abuse, National Institutes of Wellness.

Once in the synapse, neurotransmitters swim across it and adhere themselves to receptors on the surface of the receiving (postsynaptic) cell. Depending on the neurotrans-mitter, the attachment commands the postsynaptic cell to either do something or not do something. (The nature of the "something" also depends on the neurotransmitter.) Once information technology has carried out its task, the neurotransmitter is broken up by enzymes or vacuumed upward by a transporter molecule and stored for reuse by the presynaptic cell that released it.

Later on dopamine has been ejected into a synapse, it normally doesn't remain there long; the presynaptic neuron'due south transporter sucks it right dorsum upwards. But addictive drugs interfere with normal dopamine handling, prolonging its sojourn in the synapses and then its agreeable sensations. Some drugs practice this by forcing the presynaptic jail cell to release more than the usual amounts of dopamine, others by preventing re-uptake past the transporter; some may fifty-fifty do a little of both. Cocaine, for case, imitates dopamine so well that it can bind to the transporter and block dopamine re-uptake. Amphetamines reverse the transporter's normal function, preventing re-uptake while likewise using the transporter to pump additional dopamine into the synapse from the presynaptic jail cell.

As with the other substances in its chemistry prepare, the brain unremarkably keeps strict control over supplies of dopamine. Too little, and people will develop the tremors and characteristic stoop of Parkinson's affliction. Too much may be responsible for the visions and delusions of schizophrenia. Simply the right amount of dopamine, scientists think, creates our subjective feelings of enjoyment, delight, fifty-fifty rapture—not just from drugs, simply when we are eating ice foam, or making love, or getting a compliment. Defined biochemically, bliss is what we feel when that bolt of dopamine lightning strikes in the nucleus accumbens.

Addictive drugs share 1 pivotal characteristic: they all increase brain levels of dopamine. Many of the effects of the stimulants amphetamine and cocaine can exist explained by their ability to elevate synaptic levels of dopamine and block the dopamine transporter, observes Marina Wolf, who studies addiction in rats at the Chicago Medical School in N Chicago. "So it was logical to go from the importance of dopamine systems in the astute actions of these drugs to proposing that the adaptations that occur when the drugs are given chronically—from the cellular level all the way up to a behavioral level—might be attributable to changes within the dopamine arrangement," she says.

Opioids too stimulate release of abnormally big amounts of dopamine, employing 1 of nature's intricate juryrigged contraptions. Dopaminergic neurons in the ventral tegmentum are regulated by other neurons that go on them from releasing besides much dopamine. Those regulatory neurons are studded with opioid receptors; when drugs such equally morphine lock on to those receptors, they inhibit the inhibitory neurons. That is, they prevent the neurons from doing their normal job of holding down dopamine product, resulting in the release of large amounts of dopamine.

Nicotine probably activates both the dopamine and opioid overproduction systems, but the details are not yet clear. Ethanol, too, appears to use the opioid method of disinhibiting dopamine neurons (in addition to its many other activities), but besides increases their firing rate in the ventral tegmentum.

In brusque, each drug makes utilise of the dopamine pathway in a unlike way and recruits other brain chemicals (including other neurotransmitters) to help. What follows is a selective and much-simplified business relationship of some consequences of the dizzyingly complicated process of addiction.

The evolution of motivation

Researchers have amassed a mount of reasons to explain drug apply. Leshner says that 72 "risk factors" have been defined, from the street toll of a drug to the drug habits of the people ane hangs out with. But the basic reason people use drugs isn't complicated or mysterious. They similar the manner drugs make them feel.

Scientists believe, however, that the advantage pathway exists for reasons more fundamental than fun. Information technology does, after all, comprise receptors, transporters, and other molecules that normally hitch up non with drugs but with the chemicals that evolution has designed for them. Scientists have known that the brain produces these "natural" psychoactive drugs since the 1970s, when the enkephalins, the first of the opioid peptides, were discovered. Since then, researchers accept identified the natural brain analogs of all of the major drugs of abuse.

Scientists believe activation of the reward pathway is an essential spur to motivation, an incentive to acquire and repeat adaptive behavior that they call reinforcement. Eating may be pleasurable, just its underlying purpose is to sustain life; the pleasure that accompanies delightful flavors and full bellies is an enticement that encourages creatures to make a habit of it.

The encephalon contains other circuits that interact with the reward pathway to encourage adaptation and survival, circuits that bargain with emotion and learning. These circuits assign significance and meaning to experience—to individuals, things, and events in the world. Doing and so requires computing, for example, whether something is hazardous, or edible, or sexy, and and so adjusting encephalon function to generate adaptive tactics, such equally flight, approach, or courtship.

Using PET (positron emission tomography) scanning, researchers at the National Institute on Drug Abuse detected the activation of brain regions implicated in sure forms of memory when human volunteers who abuse cocaine were exposed to drug-related cues (drug paraphernalia and a videotape of cocaine users). Brain activation (increased neural activity) was detected as an increase in glucose metabolism, every bit indicated by the color scale at the lower right. The drug-related cues did not produce brain activation in control subjects (scans non shown), just volunteers who experienced a high level of cue-induced cocaine craving showed encephalon activation in the dorso-lateral prefrontal cortex (DL; upper scans), which is important in short-term retention, and in the amygdala (AM; lower scans), which is implicated in emotional influences on memory. When these volunteers were exposed to neutral (not-drug related) cues, this activation was not seen (scans at left). Image republished with permission from Grant S, et al. 1996. Proceedings of the National University of Sciences USA 93: 12040-12045.

Assigning significance and meaning to feel also requires storing memories of those tactics—successful and unsuccessful—every bit a guide to adaptive behavior in the future. In short, it requires learning. As an aid to this learning, the brain links experiences with emotions; we tend to retrieve best the experiences that are accompanied by strong sensations such equally the euphoric rush from that dopamine zap in the nucleus accumbens. In fact, researchers now think that dopamine'south chief role may exist less to produce pleasure direct than to focus attention on events that portend advantage (such as the dinner bong) or possibly fifty-fifty distress (such as nausea) to facilitate learning and remembering.

The anatomy of addiction

With plenty reinforcement, drug users move on to the stages of addiction known as peckish and dependence. Dependence is an ambiguous word, sometimes used to mean physical and sometimes psychological dependence. Yet these are very unlike states, and—possibly not surprisingly—they utilize different parts of the brain.

Drugs can cause a host of changes to parts of the brain that command body functions, specially the brain stem and spinal cord. These alterations produce physical dependence on the drug. When the drug supply stops, the outcome can exist a sickness called withdrawal. Withdrawal from heroin is a ghastly experience, and alcohol withdrawal tin can actually be fatal.

A natural brain chemical compound called BDNF (encephalon-derived neurotrophic factor) tin "rescue" dopamine-producing neurons from alteration past morphine. At left is a normal dopamine-producing neuron in the ventral tegmental surface area of a rat's brain. Repeated administration of morphine shrinks the neuron perceptibly (middle). Still, when BDNF is administered forth with morphine, no shrinkage occurs (right). Photos: Eric Nestler.

Historically, withdrawal illness has been regarded as the telltale sign of an addictive drug. Many researchers, however, now reject concrete withdrawal symptoms as a defining feature of habit considering it turns out that a drug tin can be powerfully addictive without causing serious withdrawal sicknesses. Two such drugs much in evidence today are cleft cocaine and methamphetamine.

All addictive drugs alter neurons. Some of these changes appear to contribute to signs of psychological dependence when the drug is stopped, such every bit low and craving. These two sensations in item are now believed to spur addicts on in their compulsive pursuit of drugs. This irresistible desire has replaced withdrawal symptoms every bit the new hallmark of habit.

Habit and dopamine receptors

Studies of dopamine receptors are helping to shed light on the physiology of craving. There are 2 major classes of dopamine receptors, co-ordinate to David Self, of Yale Academy. He calls them Dl-like and D2-like. Self and his colleagues, who study habit in rats, report that the two receptor types have sure structural similarities and that their within-cell signaling systems are similar, but they take different anatomical profiles: They tend to be in the same brain regions, but sometimes on unlike cell types.

Self and his colleagues have found evidence that these two classes of dopamine receptors also function differently in addiction in rats. Peckish and relapse seem to involve D2 activation almost exclusively, although both receptors are activated during reinforcement. Self hypothesizes that each receptor is involved in a different motivational phase of the reinforcement process, which he calls appetitive (D2) and consumatory (Dl). "I like to utilize the terms 'seeking' and 'having.' You can think of D2 receptors as stimulating seeking, whereas Dl receptors stimulate having," he says.

Self's animal studies have gotten confirmation of a sort from studies on humans by Margaret Haney and her colleagues at Columbia University. Looking for possible treatments for addiction, they institute that pergolide, which occupies both kinds of receptors, reduced a dozen heavy coke users' subjective experiences of being high and even their heart rates, merely it had no effect on cocky-administration of cocaine and actually increased peckish. The grouping also studied ABT-431, another possible therapeutic agent, which selectively occupies the Dl receptor. This drug also significantly reduced feelings of being loftier in nine cocaine smokers and had no issue on self-administration. Just its effect on peckish was more cryptic. There was a tendency for ABT-431 to decrease cocaine peckish, although it failed to achieve statistical significance.

"Thus, D2 activation increased drug craving while Dl activation did not," Haney acknowledges. She is non, however, convinced that Self's hypothesis is correct because she suspects that, at the low doses she used, pergolide acted selectively at the D2 receptor, yet, similar ABT-431, it did non affect self-administration.

But Cocky says Haney'due south findings fit the hypothesis that the two receptors, although they seem to be doing similar things in stimulant and reinforcing effects, are doing opposite things with regard to appetitive versus consumatory behavior. "I call back it is useful to make a distinction between reinforcement and reward, appetitive versus consumatory behavior. Those terms are often interchanged, and they shouldn't exist," he says.

Addiction and the dopamine transporter

Although the details may accept been disputed, the central role of dopamine in addiction withal seemed firmly established. And then last May came research that appeared at first glance to contradict the notion that dopamine underlies addiction. "The leading hypothesis for how cocaine works in the brain appears to exist incorrect," said The New York Times. The headline in Nature Neuroscience asked: "Difficult knocks for the dopamine hypothesis?"

Marc Caron, of Knuckles University Medical Middle, and his colleagues had genetically engineered mice that completely lack the transporter for immigration dopamine out of its synapses and thus have perpetual high levels of extracellular dopamine. These knockout mice should non accept been interested in cocaine. But they were; the researchers were able to teach the mice to self-administrate the drug, Caron's group suggested that cocaine interacts with targets other than the dopamine transporter, and that the serotonin transporter could possibly initiate and sustain cocaine self-administration in the mice.

Caron points out that pharmacologists have known for a number of years that many psychostimulants are capable of blocking not only the ability of the dopamine transporter to re-uptake dopamine and therefore increment extracellular dopamine concentration, but as well the power of the norepinephrine transporter to re-uptake norepinephrine and the ability of the serotonin transporter to re-uptake serotonin. Previously, the furnishings on other neurotransmitter systems were not idea to exist important considering many of the reward mechanisms can be blocked by blocking the dopamine system.

What the study suggests, Caron says, is that addiction does not depend solely on the ability of cocaine to raise the concentration of dopamine. "It's probably much more that cocaine interacts with many other systems," he says, noting the possibility that norepinephrine might too be involved.

In normal mice, Caron says, cocaine probably likewise raises levels of serotonin, which in some way is capable of modulating the dopaminergic responses. The genetically engineered mice are allowing researchers to tease out the contribution of the serotonin organisation to the regulation of the dopamine system. Pharmacologic studies, which are often plagued by a drug's lack of selectivity, take yielded cryptic results on how—or even whether—serotonin interacts with the dopamine system. By dissimilarity, Caron notes, 1 of the advantages of genetic manipulation is that it permits researchers to exist highly selective in the effects that they cull to investigate.

Of the dopamine transporter knockouts, Haney observes, "I don't think the Caron study lone negates the dopamine theory of addiction; there are also many information supporting information technology. It seems possible to me that knockout mice have dissimilar brains—different neuronal adaptations have taken identify to compensate for what is missing." She points out that about of the data implicating other neurotransmitters and neuromodulators in the habit story, including glutamate, GABA (gamma-amino-butyric acid), and endogenous cannabinoids, still support the notion that these substances exert their effects via the dopamine system.

Habit and glutamate

However glutamate exerts its effects, it is playing an increasingly prominent role in the habit story. Addictive drugs commandeer cells in the amygdala and hippocampus to construct intense emotional memories of drug experiences. These memories link the powerful pleasures of drug highs to the people, places, and paraphernalia associated with them. Thereafter these associations can by themselves trigger cravings. Indeed, one way in which alcohol and drug treatment programs help users abstain is by trying to sever these associations, creating a fresh social circle and new friends, supportive and abstemious, equally a substitute for their onetime drinking buddies or fellow drug users.

The latest brain-imaging techniques offering visual evidence of why recovering addicts may need this sort of behavior modification to replace quondam habits with new ones. PET (positron emission tomography) studies by researchers at NIDA'south intramural enquiry program in Baltimore reveal that when cocaine addicts picket videos of coke users, not only do they feel craving for the drug, but as well the parts of their brains that light upwardly are those involved in retentivity, including the dorsolateral prefrontal cortex (probably the site of "working" memory) and the amygdala. This finding suggests, the researchers say, "that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving."

Because craving and reinforcement are aspects of learning, it is non surprising that addiction researchers are interested in glutamate, the neurotransmitter well-nigh associated with the learning procedure. Indeed, every bit the principal agent of fast neuron stimulation, glutamate is at the cadre of most all brain physiology and biochemistry and is key to the most sophisticated cortical processes. Glutamate receptors in the hippocampus appear to trigger the complex pour of biochemical reactions that convert short-term memories into permanent ones, a process called long-term potentiation.

Wolf thinks that the introduction of glutamate as a histrion in addiction is logical, non but considering glutamate underlies learning, but also because the dopamine system is regulated by glutamate-containing neurons. "Forget about drugs of abuse and but retrieve of the dopamine neurons in the ventral tegmental area. One very important mode that they become excitatory drive is through glutamate-containing nervus terminals that synapse on them. And then on that end glutamate is very important in driving the cells," she says.

On the other finish of the dopamine pathway, dopamine terminals center in the nucleus accumbens. "And the other major synaptic input that those accumbens cells get is glutamatergic. There are a lot of transmitters in the accumbens, but ii of the major transmitters determining the output of the accumbens are dopamine and glutamate," Wolf points out. "The glutamate connection makes very good anatomical sense because it's working together with dopamine at the level of the accumbens to determine what the response to dopamine really is."

In the concluding decade, Wolf and her colleagues have shown that glutamate receptors participate in behavioral sensitization, the frenetic action seen in lab animals that researchers have equally a model of drug peckish. Long-term changes that occur with chronic drug assistants, she says, seem to be dependent on glutamate systems, although each drug interacts with glutamate in a dissimilar way.

Despite her concentration on glutamate, Wolf says, "I don't call back that everyone would suggest that we abandon the thought that the dopamine cells are the core of the reward pathway. I wouldn't move to describing glutamate as the master transmitter, I would stick with dopamine." She too points out that research on the role of glutamate in addiction is still in its early stages.

There is, she says, a growing consensus that habit is only another class of neural plasticity. "Glutamate seems to be important in just about every grade of neural plasticity, but in each case its specific role is a little bit unlike, and I'm sure that's going to be the example for drug addiction too."

In fact, glutamate may be just equally central to learning to become drug gratuitous as it is to becoming a user. Cocky and his colleagues take recently found that fond rats that are no longer given drugs and somewhen abandon their search for them, a miracle known every bit extinction, show changes in glutamate receptors in the nucleus accumbens. The subsequent brain changes, Self says, are not acquired by the fact that the rats have been cocaine users, considering the researchers don't encounter those changes in rats that continue to use cocaine. And the changes are not caused by withdrawal from cocaine because they are not seen in rats that have gone through withdrawal just not the extinction procedure.

His conclusion? "[The brain changes are] caused by the experience of extinction," he says. "This is another type of neural adaptation. There are changes in the brain that are direct pharmacological effects of the drug. There are other changes in the brain that are the result of experience. Learning, in brusk. And these interact."

Indeed, Peter Kalivas and his colleagues at Washington State University at Pullman have proposed that whereas pharmacology is largely responsible for producing paranoia in cocaine users, craving and relapse are mostly the outcome of learning.

"It'due south sort of a round affair," Self says. "Taking drugs changes the brain through both learning and direct pharmacological effects. How then exercise those changes touch on motivation for subsequent drug taking or, in the absence of the drug, drug seeking and drug craving?"

Addiction within neurons

Some researchers hope that knowledge about the interaction of pharmacology and learning will emerge by paying less attention to what goes on between encephalon cells and more to what goes on inside them. The newest frontier in habit enquiry is, therefore, signal transduction: the process by which events on the outside of a postsynaptic neuron influence events inside information technology. Binding to a dopamine receptor, for example, unleashes a chain of events in the jail cell that culminate in an society to a cell's genes to change what they're doing.

Neuroscientists of all sorts accept paid intense attending to a crucial link in this concatenation, an intracellular signaling chemical called cyclic adenosine monophosphate (military camp), because it turns genes on and orders them to make some very consequential proteins. These are the proteins that assistance form new synaptic connections between neurons—the basis for long-term potentiation.

Addiction researchers have investigated camp'due south role in diverse regions of the brain, including the nucleus accumbens, where chronic exposure to morphine accelerates activity in the campsite pathway. One issue appears to be increased levels of a molecule nicknamed CREB (short for cAMP response element bounden protein)—the molecular switch that governs production of synaptic proteins and so converts short-term into long-term memories. CREB and the army camp pathway almost certainly play a part—perhaps a cardinal function—in forming the memories that researchers suspect are fundamental to craving and relapse.

Eric Nestler and his colleagues at the Yale University School of Medicine have suggested that CREB-mediated factor transcription in the nucleus accumbens serves as a kind of drug advantage rheostat. They showed that CREB regulates nucleus accumbens expression in vivo of the rat gene for dynorphin, an endogenous opiate, concluding that opiate receptors play a role in both cocaine reward and aversion to information technology. Repeated exposure to cocaine, they say, up-regulates dynorphin expression through the military camp pathway—via the dopamine Dl-type receptors. Enhanced dynorphin release could eventually inhibit dopamine release via opioid receptors on the terminals of dopaminergic neurons. "Diminished release of dopamine in the nucleus accumbens may be aversive, or information technology may unmask other actions of cocaine that oppose drug advantage," they say. This interpretation could explicate why, over time, human being addicts tend to discover cocaine less rewarding and more likely to crusade anxiety, irritability, and other unpleasantness.

Most of the neuronal adaptations generated by the drugs that have been studied and so far have involved second-messenger systems, especially military camp, just researchers are too investigating other ways that the encephalon remodels its ever-malleable neurons. This approach has led them to neurotrophic factors. Once thought to exist active only during the earliest stages of nerve jail cell growth and evolution, neurotrophic factors are now believed to be essential to the adult brain as well, where they are involved in signal transduction and neuron growth and maintenance.

Neurotrophic factors might even be able to repair a drug-damaged brain. Nestler's lab has reported that chronic morphine administration reduces the size of dopamine-producing neurons in the rat ventral tegmentum by 25 pct on average while making no obvious changes in other kinds of neurons in that region. This shrinkage may exist ane mode in which the rat encephalon tries to conform its dopamine supply to a flood of opiates, Nestler suggests. Just infusions of BDNF (encephalon-derived neurotrophic gene) into the ventral tegmentum not only prevent opiates from shriveling the dopamine neurons (perchance past ratcheting down the speedup in the camp pathway that opiates induce), only tin can even restore those neurons to their one-time plump state.

The dopamine pathway is not the xanthous brick road

Neuroscientists believe that their inquiry is at terminal going to enable serious progress on this ancient human being affliction. The common pathway was a benchmark revelation, in part because information technology offered a unified framework for studying what for a long time had seemed like a hodgepodge of unrelated behaviors.

Important though it may be for agreement addiction, the dopamine pathway itself does not seem likely to yield promising new medications or other treatments for addiction. The pathway is so essential to normal operation, to the everyday pleasures of life, and mayhap to learning itself, that it may exist nearly impossible to interfere with information technology successfully. "Whatever y'all do to the dopamine system, you e'er get more than you bargained for," Caron observes. "That'due south because of lack of selectivity and our lack of central understanding of which protein of the dopamine organisation really mediates the addictive beliefs."

And although genes seem more and more probable to play a key function in addiction, identifying these genes will non necessarily lead to treatments either. "There'southward not going to exist a single gene that's defective in people that have more liability to become addicted. Y'all probably can have many, many changes in the brain that will all eventually manifest themselves in addictive personalities," Caron says.

Researchers are hopeful that understanding the differences in the way the encephalon handles the various psychoactive agents will assist them identify suitable points of attack. Leshner cautions audiences constantly against the hope of a magic bullet against addiction. But in the next few years, there may be real progress in treating and peradventure even preventing this particularly human affliction, one that is equally onetime every bit the first Paleolithic brewers and as new as the latest mind-bending molecule from the designer druggist's clandestine chemistry lab.

Author notes

Scientific discipline writer Tabitha 1000. Powledge is the author of Your Brain: How You Got Information technology and How Information technology Works (Scribner, 1995).