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The Brain: Understanding Neurobiology

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Lesson 4—Drug Abuse and Addiction

Long-Term Effects of Drugs on the Brain

Transcript for Long-Term Effects of Drugs On the Brain Video

The human brain weighs about three pounds and influences everything a person does. You may not realize it, but your brain is not the same today as it was yesterday or last month. The brain is a continuously changing collection of cells. When you learn something new or have a new experience, new synapses form. Some synapses get stronger, or some synapses may even disappear. Your brain even enables you to feel pleasure. Whenever you do something that you enjoy, such as eating your favorite snack, drinking a cold drink on a hot summer day, or laughing with your friends, the reward pathway in your brain is activated. It is that stimulation of the neurons in the reward pathway that makes you feel good.

Drugs of abuse act on the neurons in the reward pathway. Drugs increase the release of dopamine from the neurons. The increased dopamine levels give drug abusers the rush or a high that they enjoy for a short time. The feelings of pleasure the drugs create only last a short time, but drugs can cause changes in the brain that last a very long time. Some of the changes may even be permanent.

One of the changes that occurs when a person takes drugs is the development of cravings. If a person takes drugs and then stops taking them, he or she will crave the drug. In other words, the individual will have a strong desire to take more of the drug. Drugs exert such a strong effect that even the mention of drugs may stimulate cravings in drug abusers.

Does the brain change when a person experiences cravings? The PET image on the left shows the brain of an addict who is watching a nature video with pictures of mountains, trees, and animals. Compare that with the PET image on the right showing the addict’s brain in response to a video that shows pictures of drug paraphernalia. When the drug addict sees the images of drugs or items associated with drugs, a part of the brain called the amygdala is activated. Because the amygdala is critical for memory functions, even stimulating a memory can trigger an uncontrollable urge for drugs.

As you have learned in previous activities, on a short-term basis, drugs of abuse alter the release of the neurotransmitter dopamine. But what happens when a person takes drugs over a period of time? Does the body respond to them in the same way it did when the person tried the drugs for the first time? Often, the individual doesn’t get as intense of a response after taking drugs repeatedly. This is called “tolerance.” The brain has adapted to having a certain amount of the drug present and doesn’t respond the same way it did initially. The body may become more efficient at metabolizing or breaking down the drug. This reduces the amount of drug in the bloodstream. Or, the cells of the body, and the brain can become more resistant to the effect of the drug by causing changes in the activity of the receptors. Tolerance explains why drug abusers and addicts take increasingly higher doses of drugs over time.

Remember that although it is the drug’s effects on the reward pathway that cause the abuser to feel the rush or euphoria, drugs affect many other parts of the brain. For example, when someone smokes marijuana, THC, the main psychoactive chemical in marijuana, localizes to many brain regions. The blue spots in this image indicate places in the brain where THC binds to its receptors. THC does not affect only the reward pathway, it affects many parts of the brain.

How does the THC distribution in the brain compare to the localized functions shown in this diagram? How does the presence of THC in these areas affect human behaviors? When the THC in marijuana acts on the neurons in specific brain areas, it changes the way the neurons function. When the neurons don’t function normally, this results in changes in a person’s behavior that are regulated by those neurons. That explains why marijuana use changes a person’s abilities in movement, balance, coordination, memory, and judgment. These are body functions controlled by the brain areas where THC acts.

Some of the long-term effects of drugs are very profound. You may have heard that drinking alcohol kills brain cells. It’s true. If a person abuses alcohol over a period of time in high amounts, some neurons in the brain will die. The mamillary bodies, groups of neurons in the brain associated with memory functions, are sensitive to the effects of alcohol. Neurons in the cortex, the part of the brain that controls most of our mental functions and gives us our consciousness, also can be killed by alcohol.

The drug MDMA, a stimulant commonly called Ecstasy, causes dramatic changes in brain activity. The top set of PET images shows the brain of a person who does not take drugs. The bottom set of PET images shows the brain of an individual who used MDMA for an extended period up to three weeks before the images were taken. Unlike the other PET images you have examined, these images measure the brain’s ability to transport serotonin, a neurotransmitter that regulates many body functions, including learning, sleep, appetite, and emotions. The duller colors in the MDMA images indicate that serotonin transport is reduced in the brain of an MDMA user. The images of the drug abuser’s brain certainly are different than the non-drug abuser’s brain. Findings like this suggest to scientists that MDMA use may increase the risk of long-term problems with learning and memory.

In other studies, scientists have determined that MDMA can kill neurons. In these images taken of the brains of squirrel monkeys, scientists have used a fluorescent dye to label the axons of neurons that produce serotonin. The neurons that produce serotonin appear white in these micrographs. Neurons that produce a different neurotransmitter do not show up at all. How do the pictures labeled B and C compare to the picture labeled A? In the cerebral cortex, there are many fewer labeled axons after MDMA use. Even 18 months later, the number of fibers is still greatly reduced.

How does a different region of the brain react after MDMA use? In the hypothalamus, for example, there is a decrease in serotonin axons two weeks after MDMA use, as shown in the photograph labeled E. In this part of the brain, however, 18 months after MDMA, as shown in picture F, the number of labeled serotonin axons is approximately the same as in the control, as shown in picture D. Even though the number of axons is back to normal, scientists don’t know if the neurons function differently than they did before MDMA use. Scientists currently do not know if MDMA kills neurons in the human brain.

Cocaine, like methamphetamine, is a stimulant that can have powerful effects on the brain and body. But how does it affect the brain over a long period of time? Can you tell which of the PET images shown here is of a normal brain and which one is of a cocaine addict’s brain? Neurons that are the most active metabolize more glucose and are shown in red. The image on the left is the brain of a person who had never taken cocaine. The image on the right shows how cocaine decreases the activity of the brain.

After taking cocaine, the high wears off after about 30 minutes, but the brain is not the same as it was before. Once a person is addicted to a drug like cocaine, the brain is affected for a long time. In fact, the brain really is changed. These PET images show how cocaine affects the brain even after a person stops abusing drugs. Look at the brain of a cocaine abuser ten days after the last use of cocaine. How does the brain compare to a normal brain, that is, the brain of someone who has not abused drugs? Like most of the PET images you have examined, these measure glucose utilization and tell us about brain activity levels. The areas in red are most active. Even ten days after the last abuse of cocaine, the levels of activity in a drug abuser’s brain are much lower than those in the normal brain. How long do these changes in the brain last? Even 100 days after the last cocaine use, the drug abuser’s brain is much less active than the normal brain. That is over three months later. Scientists wonder if there are areas in the brain that never fully recover from the effects of drugs.

Scientific investigations reinforce the fact that drug addiction is a brain disease. Drugs really do change the way the neurons in the brain work. Scientists don’t know all of the answers, though. Researchers continue to investigate how drugs exert their effects. But they must deal with several issues that make answers more difficult to find. First, each person responds to drugs differently. Not everyone who experiments with drugs will become addicted. An individual’s genetic makeup undoubtedly plays a part in determining whether a person becomes addicted to drugs. Second, many drug abusers abuse more than one drug. Individuals who take cocaine, for example, may also drink alcohol. Taking more than one drug at a time makes the consequences of drug abuse more unpredictable. Third, addicts often have other health problems in addition to drug addiction. Heroin addicts, for example, spend a lot of energy trying to get their next fix. Their search for drugs takes over their lives. They don’t eat right. They may have weak immune systems, and they often suffer from mental illnesses such as depression.

The brain is an incredibly complex and continually changing organ. This complexity will keep scientists working for many years to understand what the brain does and how it does it. Someday, continuing scientific investigations will answer the questions about what happens in the brain to cause addiction and also will answer the questions about how to prevent drug addiction.

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