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Drugs of abuse activate these same VTA and nucleus accumbens neurons; that is why drugs produce pleasurable feelings to the drug user. And, because the feelings are pleasurable, the user wants to continue to experience the pleasure that he or she felt during previous drug use. One of the reasons that drugs of abuse can exert such powerful control over our behavior is that they act directly on the more evolutionarily primitive brainstem and limbic structures, which can override the cortex in controlling our behavior.
Different drugs of abuse affect the neurons of the reward system in different ways. The activities in Lesson 3 in this module will elucidate the mechanisms by which drugs of abuse exert their effects.
 Figure 1.5: When an unstable positron collides with an electron, the particles are annihilated and two gamma rays are emitted at 180° from each other. Detectors record gamma ray emission to localize the site of positron annihilation. |
Scientists increasingly use newer technologies to learn more about how the brain works and how drugs of abuse change how the brain works. Historically, scientists could examine brains only after death, but new imaging procedures enable scientists to study the brain in living animals, including humans.
One of the most extensively used techniques to study brain activity and the effects of drugs on the brain is positron emission tomography (PET). PET measures the spatial distribution and movement of radioisotopes in tissues of living subjects. Because the patient is awake, the technique can be used to investigate the relationship between behavioral and physiological effects and changes in brain activity. PET scans can detect nanomolar concentrations of tracer molecules and achieve spatial resolution of about 4 millimeters. In addition, computers can reconstruct images obtained from a PET scan in two or three dimensions.
PET requires the use of compounds that are labeled with positron-emitting isotopes.4,5 A cyclotron accelerates protons into the nucleus of nitrogen, carbon, oxygen, or fluorine to generate these isotopes. The additional proton makes the isotope unstable. To become stable again, the proton must break down into a neutron and a positron. The unstable positron travels away from the site of generation and dissipates energy along the way. Eventually, the positron collides with an electron leading to the emission of two gamma rays at 180 degrees from one another. The gamma rays reach a pair of detectors that record the event. Because the detectors respond only to simultaneous emissions, scientists can precisely map the location where the gamma rays were generated. The labeled radioisotopes are very short-lived. The half-life (the time for half of the radioactive label to disintegrate) of the commonly used radioisotopes ranges from approximately two minutes to less than two hours, depending on the specific compound. Because a PET scan requires only small amounts (a few micrograms) of short-lived radioisotopes, negative pharmacological effects are imperceptible.
 Figure 1.6: Photograph of PET imaging equipment. Photo courtesy of UCLA School of Medicine. |
PET scans can answer a variety of questions about brain function, including the activity of neurons. Scientists use different radiolabeled compounds to investigate different biological questions. For example, radiolabeled glucose can identify parts of the brain that become more active in response to a specific stimulus. Active neurons metabolize more glucose than inactive neurons. Active neurons will emit more positrons. This will show as red or yellow on PET scans compared with blue or purple in areas where the neurons are not highly active. PET also helps scientists investigate how drugs affect the brain by enabling them to
Different Neuroimaging Techniques Provide Different Information about the BrainPET scanning is a major neuroimaging technique used in drug-abuse research. However, researchers also use other techniques when those techniques answer a scientific question. Similar to PET, single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and electroencephalography (EEG) are noninvasive procedures that can measure biological activity through the skull and reveal the living brain at work.4,8 Each technique has its own advantages, and each provides different information about brain structure and function. Scientists often use more than one technique when conducting their research studies.
Similar to PET, SPECT imaging uses radioactive tracers and a scanner to record data that a computer constructs into two- or three-dimensional images of active brain regions. Because the tracers used in SPECT take longer to deteriorate than those for PET, longer periods of time between tests are required for SPECT. While PET is more versatile than SPECT and produces more detailed images with a higher degree of resolution, SPECT is much less expensive than PET and can address many of the same drug-abuse research questions. MRI uses magnetic fields and radio waves to produce high-quality two- or three-dimensional images of brain structures without injecting radioactive tracers. In this procedure, a large cylindrical magnet creates a magnetic field around the research volunteer's head, and radio waves are sent through the magnetic field. Sensors read the signals, and a computer uses the information to construct an image. Using MRI, scientists can image both surface and deep brain structures with a high degree of anatomical detail, and they can detect minute changes in these structures over time. A modification of this technique, called functional MRI (fMRI), enables scientists to see images of blood flow in the brain as it occurs. fMRI provides superior image clarity along with the ability to assess blood flow and brain functions in just a few seconds. However, PET retains the advantage of being able to identify which brain receptors are being activated by neurotransmitters, abused drugs, and potential treatment compounds. EEG uses electrodes placed on the scalp to detect and measure patterns of electrical activity in the brain. The greatest advantage of EEG is speed: It can record complex patterns of neural activity occurring within fractions of a second after a stimulus has been administered. The drawback to EEG is that it does not provide the spatial resolution of fMRI or PET. Researchers often combine EEG images of brain electrical activity with MRI scans to localize brain activity more precisely. |
In addition to its uses in research, PET also is a powerful tool for diagnosing and monitoring certain diseases.7 For example, PET scans may be used to locate tumors in cancer patients, monitor the spread of cancer, and evaluate the effectiveness of cancer treatment. PET scans are able to reveal the presence of tumors because of the rapid metabolism characteristic of cancerous cells. PET images reveal increased glucose utilization by cells that have high metabolic rates. PET is an accurate test for coronary heart disease because it can detect areas of diminished blood flow to the heart. Doctors also employ PET to reveal changes in the brain that occur with Alzheimer's disease, Parkinson's disease, and seizure disorders. PET is a valuable tool because it
| Activity Number | Web Version |
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Activity 1 |
No |
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Activity 2 |
Yes |
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Activity 3 |
Yes |
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Activity 4 |
No |
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Activity 5 |
No |
| For the class | For each group of 3 students | For each student |
|---|---|---|
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1 transparency of Master 1.3, PET Image Tasks 1 transparency of Master 1.4, Major Regions of the Brain 1 transparency of Master 1.5, Areas of the Cerebral Cortex and Their Functions 1 transparency of Master 1.7, The Reward System |
1 copy of Master 1.1, Positron Emission Tomography (PET) Imagesa 1 copy of Master 1.2, Interpreting PET Images |
1 copy of Master 1.6, What Happened to Phineas Gage? |
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aThe Web version of Activity 2 is the preferred approach. Copies of Master 1.1, Positron Emission Tomography (PET) Images, are needed only if the Web site is unavailable for classroom use. If needed, make one set of color photocopies for each group of three students. Several field-test teachers laminated the color copies to help preserve them. |
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| Activity Number | Material |
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Activity 1 |
6 to 8 index cards (3" x 5" or 4" x 6") |
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Activity 2 |
Overhead projector |
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Activity 3 |
Overhead projector |
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Activity 4 |
None |
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Activity 5 |
Overhead projector |
Prepare task cards for Activity 1, Step 1 (see below). Decide which tasks you wish students to do. Write the instructions for each task on an index card.
Arrange for the class to use the computer lab for Activities 2 and 3.
 This
activity is designed to engage students in learning about the brain and
to help the teacher assess the students' prior knowledge of the scope
of functions regulated by the human brain. |
1. Ask for six to eight volunteers (one for each task) to participate in an activity. Ask them to come to the front of the room, and give each volunteer one of the prepared task cards. Then ask each volunteer, one at a time, to perform the task listed on his or her task card.
The specific tasks can and should be very diverse. The following list suggests some appropriate tasks:
2. After the volunteers perform the tasks, ask the students to identify the part of the body that is involved in all of the tasks.
The goal for this question is for students to acknowledge that the brain is involved in regulating all human physiological, behavioral, and emotional functions. For example, point out that all students are breathing. When most people think about breathing, they think about the lungs, but not the involvement of the brain. Also, point out that each student's heart is beating. Although the heart is actually pumping the blood, the brain fulfills an important role in regulating the heartbeat. The involvement of the brain will be more obvious for some of the tasks than for others.
3. After students deduce that the brain is involved in all of these activities, ask students to suggest how they think scientists investigate what happens in the human brain.
Students will provide a variety of answers, including watching a person's behavior, electrical shocks, various imaging techniques (such as PET scans, CT scans, or MRI), using animals (either living or dead) for research, and so forth.
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