Addiction has stood to be an age-old social quandary, ravaging many lives and leaving towns, families, and people themselves desolate. But what does a habit or substance actually do to a person’s brain that propels him to go great lengths– that is to the point of losing his freedom or even his life– just to have it? Exploring what goes on inside the mind of an addict provides a better understanding as to why and how he gets hooked. Scientists have unraveled the mechanisms behind addiction and begun to make sense of it.
Understanding the Neuroscience of Need
During the past 10 to 15 years, there has been a major shift in the way addiction is perceived. What used to be considered as a moral or character flaw has now evolved to a new appreciation that it is, in itself, a maladaptive form of learning. Similar to riding a bike, addiction cannot be quickly unlearned.
Keith Humphreys, senior White House drug-policy adviser and professor of psychiatry and behavioral sciences at Stanford University, draws the similarities between losing weight and conquering addiction, emphasizing that as the body changes, losing weight can become bigger of a hurdle than it was before you gained weight in the first place. Because addiction-associated brain changes are long enduring, many people are bound to relapse, hence the longer course of treatment.
Stanford neuroscientist Rob Malenka, MD, PhD, who pursues his research using animal subjects to extrapolate to humans, has provided some vital biological insights on addiction. He notes that there are things that a person can and cannot forget. For someone who is an addict, the drug experience — not just the substance, but the entire “scene” as well — becomes indelibly etched into the physiological brain circuitry, driving the person onward through the hurdles of existence. However, much of that memory cannot be any farther from the truth. Since all addictive drugs appear to have a common mysterious component, they seem to be better than the real thing, even than the primal purpose of the brain’s reward circuitry: food, sleep, sex, friendship, novelty, etc. To an addict, it would feel better, in fact even better, than it was the last time around.
It is further explained that addictive drugs simulate natural rewards like food and sex by igniting a network of brain areas collectively referred to as reward circuitry, which is responsible for enjoyment– which if a person thinks about it, serves as a crucial survival response. It pushes a person to do more of the things that would keep him alive and to lead to producing more children: food intake and ingestion; hunting and hoarding; choosing a mate and actually procreating.
These drugs kindle the reward circuitry in a way that natural rewards can’t seem to. Eventually, the need for the drug intensifies; it becomes so much more than the mere pleasure the user obtains from it. By the time the excitement is gone, the key regions of the brain may have already produced long-lasting–or maybe even irreversible–changes in them.
Addiction was once defined in terms of physical symptoms of withdrawal: nausea and cramps in the case of heroin addiction; or delirium tremens in the case of alcoholism. All these have physiological changes within the cells of an addict’s body. That has changed over the years; addiction is now seen in terms of brain circuits: the neurophysiological changes that are obtained from learning and experience. A person craves, seeks, and uses drugs again and again despite knowing the grave repercussions of doing so, not only because he has the memory of it being more wonderful than anything else, but also because his brain has been reprogrammed, that in the event that it gets exposed to anything that reminds the person of the drug, he will feel rotten if he won’t get any.
Malenka sees these as symptoms of a brain disease, not a mere weakness of will. He and other researchers have been working to see addiction as rather a sum of behavioral consequences of changes within neurons that happen with repeated exposure to drugs. Over time, such sub-cellular changes alter the circuital connections, especially hardwiring the casual desire for drugs into a vicious craving that is easily triggered not only by the drugs, but by environmental factors as well– people, places, situations, et al– even when the user hasn’t been exposed to drugs for month or even years.
The Feel-Good Brain Chemical Called Dopamine
Dopamine is among a growing number of known neurotransmitters, chemicals the neurons produce for the purpose of relaying information from one neuron to another. Different sets of neurons produce different neurotransmitters, which all work virtually the same way, but in different nerve bundles and with a variety of results. These chemicals are stored inside dollops of tiny bulbs sprouting from points along a neuron long, electricity-conducting axon at prime contact points a neurons shares with others.
As an electrical signal roars down the axon’s surface, it rumbles past one of these tiny bulbs; countless molecules of neurotransmitters then get ejected into the surrounding area. These neurotransmitters diffuse across that space, referred to as a synapse, to specialized receptors on the abutting nerve cell, where the interaction can either enhance or inhibit a new electrical current in the downstream neuron. These dopamine-ejecting neurons comprise a minute fraction of all neurons. But individually, they can network with up to 10,000 or more other neurons extending up to the far corners of the brain. A gobbet of dopamine in the tank can spur a person’s reward mileage, so to speak.
A person might often wonder whether drugs can activate the reward circuitry, once dopamine permeates the neurons that constitute the reward circuitry. It does.
“One reason that the advances in our study of the neurophysiology of addiction so far exceed our understanding of other psychiatric disorders is because the animal models for addiction are extremely good,” says Malenka. Train a rat to press a lever for an infusion of a drug of abuse, and you will notice the same compulsive behavior in the rat that you would in a person. “A rat will work very hard to get drugs,” he says. “It will press that lever hundreds, even thousands, of times and endure pain and suffering to get drugs.”
As the animal studies by Malenka have shown, virtually all abused substances– amphetamines, alcohol, nicotine, etc– work by interfering with the brain’s reward circuitry. They stimulate the release of dopamine in target structures such as the nucleus accumbens, which is the key structure in the experience of pleasure.
Mechanism of Opiate Addiction: Different from Other Drugs?
Chronic morphine exposure has been seen to have the opposite effect on the brain compared to other drugs. A study done on mice, provides a new insight into the basis of opiate addiction, according to Mount Sinai School of Medicine researchers. They discovered that a protein known as brain-derived neurotrophic factor (BDNF), which is abundant in cocaine addiction, is otherwise hampered in opiate addiction.
The study shows that BDNF reacts exactly the opposite way with opioid administration compared to cocaine, according to Ja Wook Koo, PhD of the Department of Neuroscience at Mount Sinai School of Medicine. Morphine is said to create reward by inhibiting BDNF, while cocaine acts by boosting BDNF activity.
BDNF is essential in several functions in both the central and peripheral nervous system, noted for generating new nerve cells and aiding in the survival of existing ones. It is also known to ignite reward circuits in the brain.
In the recent study, the research team saw that morphine suppresses BDNF in a different reward center of the brain known as the ventral tegmental area (VTA), so as to achieve reward and chronic addiction. Morphine caused a depletion of BDNF in the VTA of mice, which activate the reward circuit. On the other hand, when BDNF was administered to the VTA of mice, it impeded that reward. When BDNF was administered to the nucleus accumbens, there was no reward at all.
When the researchers evaluated the morphine-induced changes in gene expression in the nucleus accumbens, the region of the brain in which morphine elicited no reward they found that two genes, sox11 and gadd45g, interfered with the brain’s response to morphine, impeding any reward, thus no addiction.
According to Dr. Koo, the study provides crucial insight into the molecular basis for morphine addiction. It is the first to note that BDNF is a negative modulator in brain, especially in opiate addiction, compared to stimulant addiction. Albeit further research is necessary, the genes that they identified may be useful targets in preventing addiction. Data show that infusing BDNF to the VTA may be a viable treatment in counteracting opiate addiction. Furthering the study on the counteractive response of BDNF in morphine as compared to cocaine may also aid researchers in determining how poly-drug use may impact the brain.
This study was backed by grants from the National Institute on Drug Abuse and a Rubicon Grant from the Dutch Scientific Organization.
Behavioral and Substance Addiction: How Are They Related?
Behavioral addictions not only resemble substance addictions in many ways; both types also arise from the same brain processes. The most compelling parallelism between these two boils down to one thing: compulsion.
When a gambler becomes an addicted gambler, he is referred to as a compulsive gambler. Eating disorders, such as binging and anorexia nervosa, are often categorized as compulsive behaviors. The same goes for sex addiction and a few other forms. Chain smokers, alcoholics, drug addicts, gamblers have one thing in common– compulsion It is the common feature underlying substance and behavioral addictions, both in people’s behavior and in their brain mechanisms.
The individual actions a person performs repetitively when he suffers from obsessive compulsive disorder (OCD) are what considered to be the most fundamentals forms of behavioral addiction.
Naomi Fineberg, a well-known English psychiatry professor and researcher, considers OCD as the archetypical compulsive disorder: people with OCD have little or no control over their impulses; they display diminished cognitive flexibility and limited goals. She expounds on her supposition by initiating a button-pressing task, where the “reward” is switching off a mild electric shock. After training on the task, the reward is withdrawn, which makes the act itself like it has not accomplished anything at all. Yet OCD patients still keep on pressing the button; while ordinary people do not. OCD patients report that they couldn’t quit pressing simply because they couldn’t overcome the urge to. She concludes that OCD is actually not about repeating a behavior to get a reward, as nothing good is anticipated. Rather, a person compulsively does something so as to avoid punishment, which is the negative consequence of doing something not right. Negative consequence, for OCD patients, may simply be the build-up of anxiety.
Fineberg also discussed her neuroscience research. OCD patients and stimulant (e.g., coke and meth) addicts display a host of similarities in the brain scan. It shows the ventral regions of the prefrontal cortex (such as the orbitofrontal cortex) are where emotions are processed and solidified over time. These areas show reduced connections with more dorsal areas that are involved in self-control. Thus the brain becomes less capable of controlling itself.
Dr. Giacomo Grassi of the University of Florence, Italy talked about OCD and addiction as disorders triggered by “reward dysfunction,” a condition that begins with anxiety but ends up as a behavioral problem, becoming “addicted to compulsion” as he terms it. He showed brain scan images depicting how OCD patients have higher activation of the amygdala (the center for emotional conditioning) and lower activation of the nucleus accumbens — the brain center for reward-seeking — a pattern repeatedly manifested in addicts. He also highlighted a shift in activation starting from the nucleus accumbens to the dorsal striatum at the onset of compulsions, both for OCD patients and for addicts.
With the help brain scans and advances in neuroscience, we are beginning to understand the mechanisms of many human behaviors. Addiction, like many other human traits has a neurological and biochemical underpinning. Only when we truly understand the mechanisms behind addiction can we truly treat it.
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