By Julia Turan

You just received news that your best friend has a “chronic relapsing brain disease characterized by compulsive drug seeking and use, despite harmful consequences” (1).  Would it surprise you that this is just a lengthy definition for addiction?

Decades ago, society viewed addicted individuals as morally flawed and lacking in willpower. If you were an addict, something was wrong with your morals, not your health. Since then: a seismic shift. Today, we view addiction as a disease of the brain, belonging in the same category as PTSD, Alzheimer’s, and Schizophrenia.

In the first speakeasy of July 2015, Dr. T. Celeste Napier, Professor in the Departments of Pharmacology and Psychiatry at Rush University Medical Center and Director for the Center for Compulsive Behavior and Addiction, spoke about the happenings beneath our skulls during addiction, its risk factors, and the efficacy of treatment.

Starting from square one: brain anatomy and circuitry of addiction

Drugs cover a lot of ground in the brain, both diving deep and staying on the surface. The outer portion of our brain, a crinkled layer, is the cerebral cortex. The frontal section of this layer, behind our foreheads, is responsible for decision-making. “We as humans are very proud of this part of the brain,” quips Napier.

Buried beneath, lie the chunks managing our responses to memory and reward. As much as we like to believe we are rational, levelheaded beings, we are, in fact driven by rewards. If something doesn’t feel good, we have really no motivation to do it.

One of the key messengers linking these outer and inner areas of the brain is dopamine. This chemical originates in a few deeply embedded neurons that then swoop around much of the frontal parts of the brain, exerting control on the functions of these regions. Drugs interfere with the dopamine system, specifically in the space across which neurons communicate known as the synapse.

“It’s in this little space that these drugs sneak in and start to wreak havoc,” Napier explains. It seems unfortunate that our body has reward systems that drugs can powerfully lord over. Why do these “vulnerable” systems exist in the first place? It’s because we need a way to stay motivated to continue those behaviors that keep us alive and reproducing, like eating, drinking and procreating. In other words, because it feels good, we are more likely to keep doing it. Drugs upset the functioning of this essential system, leaving us seeking harmful substances as if they were vital to our survival.

Tampering with reward: drugs and the dopamine system

In the 1990s, researchers began investigating the dopamine system and reward in rats. Reward was in the form of food, sex, or drugs. Gaetano Di Chiara studied the effects of food, and found that neurons in a brain area associated with reward (nucleus accumbens) spat out dopamine right when the rats were munching (2). The same turned out to be true for sex in male rats (3) as well as drugs of abuse (4).

No matter if the rats received nicotine, morphine, cocaine or amphetamine, their brains responded as they had during eating and sex. No matter the chemical differences, each drug increased dopamine in the same reward area of the brain. The message was clear: all drugs feel pretty darn good.

More than just an increase, there was a deluge of dopamine. In response, dopamine receptors (the molecules on the “listening” end, which respond to the dopamine), like catchers bombarded with too many balls, “get over-activated and start to retreat,” in Napier’s words.

Human brains show structural evidence of this change (5). Researchers looked at the numbers of dopamine receptors in the reward areas of addicted and non-addicted individuals. Addicts have fewer dopamine receptors, because their brains are trying to balance the overload of dopamine by becoming less responsive to the chemical.

Long-term exposure to drugs of abuse “changes the brain in fundamental, long-lasting ways,” says Napier. These include cellular changes that alter the way the brain looks and acts. “Addicted individuals are in a different state of mind,” Napier concludes.

This is all just part of the downward spiral of drug abuse. But what causes people to first experiment with drugs? There are two major objectives: to feel good – experiment, take a risk, or try something new- or to feel better – because they haven’t been feeling good. Initially, both of these decisions are voluntary attempts to change a mood or emotional state.

The question becomes: once individuals are addicted, and their brains have been functionally altered, are their decisions still voluntary? Can you just say no to drugs at this point? Napier suggests that although the answer may not be a resounding no, the individual’s capacity to make good choices is definitely compromised. The very brain regions that are involved in judgment, decision-making, and inhibitory control, are those affected by the drugs. Detailing the influence of drugs on this next modality, decision-making, will further our understanding of the sway drugs hold over us.

Fiddling with the frontal cortex: drugs and decision-making

An intricate interplay of brain areas allows us to take certain stimuli into account and make the right decision. The brain region that powers us with motivation is the orbitofrontal cortex, or OFC. Getting us out of bed in the morning and such, it receives signals from reward and memory areas. Reward includes a factor called salience, which tells how important that reward is. Properly placed salience encourages you to feed your children rather than snort cocaine. Memory is superimposed with an emotional valence by a brain region called the amygdala. Activities that involve happy and exciting feelings are likely to be repeated.

While listening to Napier’s talk, audience members’ brains looked something like this: the OFC may have been egging them on to eat the hamburger they ordered, the accumbens (the reward area we heard about in the 1990s studies) telling them how good it tastes, and the amygdala recalling the delightful burger they had last month at this venue. When these three areas try to coax this attendee to order a second burger, an area above the OFC- the frontal cortex- steps in. Like a chiding parent, it restrains the person from overeating, balancing the rest of the brain areas to make the wise decision. Do not order another hamburger.

In addicted individuals, no matter the type of drug, it is shutting down the frontal cortex. “Their judgment is going offline,” says Napier. Without the frontal cortex holding them back, the OFC, backed by the messages of reward and emotional memory, tells them to go right ahead and take the drug. In other words, “one’s capacity to make good choices is compromised directly by the drugs being abused,” as Napier explains.

Napier’s lab is working to develop compounds that will block the memory/salience signal, hopefully helping the addict want the drug less. “We believe we can come up with compounds that are going to act as anti-craving compounds,” she says.  “We think this kind of treatment will go a long way to help an addicted person to resist taking more of the abused drug.”


Tempted teenage brain: adolescence as risk factor

Not everyone is equally susceptible to addiction. If you’re in that rowdy, rebellious phase we call teenage, you are more vulnerable than those in other stages of life. Researchers are even thinking about calling addiction a developmental disease. As Jay Giedd puts it in his article, Amazing Teen Brain: “Rapidly changing wiring leads to mental agility and risky behavior” (6).

This is partly due to the timeline of brain development. The frontal cortex lags behind the development of memory and emotion centers. With the frontal cortex not impacting the decision process as much, the result is similar to the brain of addicted individual. The developing brain is more vulnerable to the damages that occur with chronic use of drugs. In other words, “the developing brain is a risk factor for substance use disorders,” Napier says.

On top of this vulnerability, parenting can certainly influence teenage brains. Napier stressed that we have to understand the balance between environmental effects and biology on brain development. Without a positive, nurturing environment, a child is at risk for having those brain regions that are important in making healthy choices, be compromised as an adult. Napier suggests that good parenting can compensate for the immature frontal cortex to help teenagers make healthy choices “without impinging on all the wonderful things that makes a teenage brain so adventurous.”

A hopeful undertone: recovery and treatment

Recovering from addiction is possible. Researchers have discovered many cellular changed associated with recovery. Dopamine transporters that sit on the surface of neurons normally pull dopamine out of the synapse to control the amount of influence the compound can have on neuronal communication. Amphetamine prevents this process, allowing more dopamine to stick around. During recovery, brain scans show the transporters making a comeback. Our brains have the capacity to heal themselves.

However, recovery is a very difficult, long process, and requires repeated treatment. “Remember, this is a chronic relapsing brain disease,” says Napier. Relapse in addiction is similar to relapse in other chronic diseases. “How many of you know a diabetic who ate a brownie? They fell off the wagon…but we don’t think they are horrible individuals,” she continues.

We view other organ diseases differently than someone who relapses into addiction. We hold a double standard for recovery from addiction, only considering an addicted individual to be cured if they don’t relapse when we remove the treatment. However, we don’t ask the same of, say, people with diabetes or high blood pressure. We understand that these chronic diseases must have chronic treatment along with healthy lifestyles to be effective.

We should think of addiction as we do other chronic diseases so that we can work to understand the biology and withhold judgment. “We want that brain to be healthy,” says Napier, “And they may need treatment for life, but maybe that’s okay.”

— Julia Turan is a science writer and C2ST volunteer. She has a degree in neurobiology from Stanford University.

Citations:

(1) http://www.drugabuse.gov/publications/media-guide/science-drug-abuse-addiction-basics

(2) Bassareo & di Chiara. Neuroscience. 89:637, 1999.

(3) Fiorino et al. J Neurosci. 17:4849, 1997.

(4) Di Chiara & Imperato. Proc Natl Acad Sci. 85:5274, 1988.

(5) http://www.drugabuse.gov/publications/finder/t/210/teaching-packets

(6) Giedd. Scientific American. 312:32, 2015.