The Addicted Brain (3 page)

Figure 1-3. A lateral (sideways) surface view of the brain shows some of the more obvious regions, and each region has its own function. The specific functions of the various brain regions have become known after centuries of studies of patients with strokes, injuries, and tumors. Drug addiction also involves certain regions. (Adapted from
http://medicalimages.allrefer.com/large/brain.jpg
, accessed on December 20, 2010.)

The brain is also the organ of awareness. When general anesthetics are administered, the electrical activity of the brain is reduced, and we lose awareness or go to sleep. If we stimulate the visual cortex, we might have visual images pop into our awareness. If the olfactory cortex is stimulated, then we might perceive odors. If we stimulate other parts of the brain, other events or sensations enter our awareness. Emotional behavior is also based in the brain. A group of brain regions collectively known as the limbic system controls emotional behavior and is partly responsible for feeling good. The following chapters link certain brain regions with feeling good and with drugs.

Science, like everything else in our lives, has become technology-driven, and there are marvelous new approaches and instruments that allow us to examine the tiniest parts of our chromosomes or peer into the depths of our brains without surgical invasion of the skull. These tools are powerful and interesting in and of themselves.

The science of genetics has advanced, and it is now possible, with a small sample of blood, to examine our genes. Because genes are the basis of heredity, and some aspects of drug addiction are heritable, studies of genes can be informative. The target of these studies is DNA, which is made up of four different chemicals called bases, and it is
the order of these chemicals in our DNA
that specifies our genes. These chemicals—abbreviated as the letters A, T, G, and C—are lined up in two parallel strands that comprise the structure of DNA. Again, it is the sequence of these bases, in groups of three, that
constitutes our genetic code, and certain parts of our genetic code can contribute to the likelihood of our becoming a drug user.

For looking inside our brains, noninvasive brain imaging techniques can be astonishing. Magnetic resonance imaging (or MRI) describes the structure of our brains, such that changes in the size of parts of our brains can be measured. Functional magnetic resonance imaging (fMRI) tells us about the functional activity of various brain regions. Positron emission tomography (PET) scanning is versatile. It can be used to reveal the activity of different brain regions or even the levels of certain brain chemicals and proteins. Overall, genetic and imaging studies are but two of the new tools that have become available over the past 25 to 35 years. These tools are out in front in the attack on drugs.

This book addresses many questions about drugs and the brain, including:

• Why is it said that addiction is a brain disorder rather than perhaps a moral failing?

• What happens in the brain of someone who uses drugs repeatedly?

• Can better medications for addicted individuals be expected in the future?

• Why is drug abuse chronic and relapsing, which is part of the essence of this disorder?

• Why are drugs so powerful that they can gain control of our behaviors, but we can’t give up responsibility for our actions?

• Will
I
become drug dependent?

• Are there differences among, men, women, adolescents, and older adults in how they respond to and experience drugs?

• Can one recover from drug addiction and be cured?

• The stigma of being a drug abuser is a problem in that it often prevents searching for treatment or dealing with the problem openly.

¹
Throughout this book, we tend to refer to addiction as a disorder, but it is also often called a disease. The definition of addiction that is used in this book focuses on continued drug use in spite of distress and negative consequences. However, the official description is given in the Diagnostic and Statistical Manual of Mental Disorders produced by the American Psychiatric Association, and it includes more elements. The DSM IV TR is the current edition used by medical professionals for official diagnoses. The DSM is an evolving document and DSM V is due in the near future. Currently, the diagnosis of drug dependence requires the presence of three or more of several symptoms, and it is possible to have a diagnosis of substance dependence without the presence of distress or negative consequences. The official list of symptoms and diagnostic criteria for Substance Dependence and Substance Abuse can be found in an online version of the DSM IV TR. One possible site is
http://www.psychiatryonline.com/content.aspx?aID=629
, which was accessed on June 28, 2011. Only a qualified professional can make a diagnosis.

²
Ibid.

³
Ibid.

⁴
An illicit drug is one that is not legal to produce, not legal to use or possess, or a medically useful therapeutic drug that is used non-medically.

⁵
Office of National Drug Control Policy (2004). “The Economic Costs of Drug Abuse in the United States,” 1992–2002. Washington, DC: Executive Office of the President (Publication No. 207303).

“I gotta get a hit. I steal money, leave work in the middle of the day to get high, and I can’t stop. What’s happened to me?”

For many years, doctors and scientists have been trying to figure out how addiction works and how addicts can be treated. The research has become sophisticated with elaborate laboratories for human subjects in many of our best medical centers. Hundreds and hundreds of publications every year describe new findings that promise a better understanding of and improved treatments for drug abusers.

Studies with animals, in addition to humans, have been helpful. In fact, using animals in research has a number of advantages over studying humans.
¹
Importantly, the environment, nutrition, general health, and drug use of an animal can be rigidly controlled since its birth, although this is not possible with humans. Because of this, animal experiments can be more carefully defined and more easily interpreted. Also, animals cannot refuse good medical care during periods of experimentation, whereas humans are not bound to follow medical advice. Animals are in controlled and protected environments, whereas we have little control over humans’ choices of environments. In addition, animals can be given new treatments and medications, and indeed, the FDA requires that animals be used for proof of safety of new medications. Despite these advantages, the use of animals in
research is not taken without care or caution. Each and every experimental procedure must be described in detail and approved by a learned committee before the experiments can be carried out.
²
Unexpected problems are studied by committees to learn how we can better care for our animal subjects. Scientists are sensitive to these issues and often have beloved pets at home.

Although animals were part of addiction research during the 1920s, this earlier research focused primarily on understanding how drugs affected the animal’s physiology. Typically, drugs were injected into animals that were held or immobilized; the animals were passive recipients. Then a variety of tests and measurements were made on the animals, and a great deal was learned that is the basis of much work today. But in a new procedure developed in the 60s and 70s, the animals were given control over their own drug injections. They actively and freely pressed a lever to get a drug injection. The rate of lever pressing reflected their desire for more of the drug and its effects. This control over drug taking is more like the situation with humans who have control over drug taking and provides a better animal model of human drug taking.

This procedure or model was developed by several scientists including Drs. James Weeks, C.R. Schuster, and Tomoji Yanagita. When animals were allowed to administer drugs to themselves by pressing a lever, they did so, and with surprising gusto! In this drug self-administration model, a catheter is placed surgically under anesthesia in an animal’s jugular vein so that a measured quantity of a drug can be delivered (by a lever press) directly to the animal’s bloodstream where it rapidly circulates to the brain. The animals appear to quickly adapt to the presence of the catheter, going about their activities probably with no more notice than a dog pays to his or her leash while out on a walk.

There are small variations on how to do this, but the idea is that an animal is placed in a sound-insulated chamber to avoid distraction and is then presented with two levers. One activates delivery of a saline solution, the other a saline solution containing a drug such as cocaine. Of course, the animal does not know it is receiving an injection, but it obviously learns that pressing the drug-related lever produces a different sensation than pressing the saline-related lever. Which lever it presses and how often it does so are clear, quantifiable measures of which sensation it prefers (see
Figure 2-1
).

Figure 2-1. Animals will self-administer drugs. The figure shows a rat that has access to levers (only one is visible), and each lever is hooked to either saline (a saltwater solution) or a drug solution such as one with cocaine. The rat also has a catheter or drug delivery tube implanted in its blood vessels. The computer controls how often and how much of the drug is given when the lever is pressed. When the drug-related lever is pressed, the rat does not know it is getting an injection, but rather it has a sensation, and if it likes the sensation, it will press the lever again and again and again. Moreover, the rat learns to ignore the lever that results in an injection of a drug-free solution. This animal model of drug self-administration is vitally important for research and understanding the how and why of addiction. (Modified from
www.pharmaco.umontreal.ca/apropos/LaboFilep/images/Self-administrationEN_000.jpg
, as accessed on February 24, 2009.)

When offered one of almost any of the drugs that humans abuse (exceptions being those that distort sensations and perceptions, such as hallucinogens like LSD), the animal almost always chooses the lever that results in drug delivery. The sensation brought about by the infusion of the drug is positive and acts as a
reward
that positively
reinforces
the act of pressing the lever. Every lever press, followed by an infusion of the sensation-producing drug, further reinforces the lever-pressing behavior. The animal appears hooked, pressing the lever repeatedly. In the case of a rewarding drug, such as cocaine, the animal might ignore food, water, or even a sexually available mate, and it presses the lever until it is too exhausted to continue. Although the animal controls the act of lever pressing, the researcher controls the total amount of drug that is administered and prevents the animal from taking enough to injure or kill itself accidentally, as sadly can happen with humans.

If the researcher suddenly reverses the levers so that the one delivering cocaine now delivers saline, the animal soon discovers the drug-related lever and starts pressing it. If the drug is removed completely, the animal keeps lever pressing for some time, apparently in the hope that it will reappear. It might require a large number of unsuccessful presses to “extinguish” the pressing behavior, meaning the animal no longer associates pressing the lever with the desirable sensation and stops.

In these controlled experiments described previously, the animals have access to a restricted amount of drug over a restricted time. But the human situation doesn’t always work that way. Sometimes drug users have access to a drug for a long, extended time. George Koob, his colleagues, and others
³
studied this in animals. They allowed some animals to have longer access to the drug. For example, rats were allowed to self-administer cocaine for either one hour or six hours per day. In the group with one hour access, cocaine intake was lower and stable over days. But the group that had six hours of access gradually
increased
its intake over days. Access and availability of a drug can
make a difference in the amount of drug that is taken. This is consistent with the behavior of heavy drug users.