their quality of life.
Medical Uses of Addictive Drugs
It is well known that otherwise safe medications can turn harmful if abused or taken without
prescription or supervision. The other side of this coin is that many drugs of abuse are themselves,
or have been found to contain, active ingredients that can be therapeutic. A good example is
morphine. During the Civil War, doctors gave morphine to wounded soldiers to relieve the pain of
injuries. Doctors didn’t realize how addictive injected morphine was until many soldiers became
addicted to the drug.2 Morphine addiction became known as “soldiers’ disease.” Today, morphine
is a valuable medicine to relieve pain when administered with the appropriate medical supervision.
Patients in hospitals receive morphine to ease their pain after surgery and during cancer and burn
treatment. Very few of these patients become addicted to morphine even though they may take it
for extended periods of time.
Another drug that has received considerable attention for its potential medical benefits is
marijuana. Television and newspaper reports periodically present stories on the use of marijuana
by terminal cancer or AIDS patients to ease their discomfort and pain. Following up on such
anecdotal evidence, several scientific studies have been able to corroborate at least some of
the claims about marijuana’s beneficial effects on appetite, nausea, and certain types of pain.
However, marijuana’s addictive properties and its usual delivery by smoke inhalation—which
exposes the lungs to many toxic chemicals—make it an unappealing candidate for medications
development. Rather, it is likely that our understanding of the biology of marijuana’s active
ingredients, such as tetrahydrocannabinol (THC), will lead to improved medications for a variety
of conditions, ranging from obesity and addiction to neuropathic pain in multiple sclerosis (MS)
patients, chronic pain in advanced cancer patients, nausea, and wasting syndrome.11
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The risk of becoming addicted to prescription pain medications is minimal
in patients who are treated on a short-term basis; however, the risk for
those with chronic pain is less well understood. Some studies have shown
that those most vulnerable to becoming addicted to prescription pain
medications have a history of psychological disorders, prior substance
abuse problems, or a family history of these disorders. Pain management
for patients who have substance abuse disorders is particularly challenging
for the medical profession. However, these patients can still be successfully
treated with opioid pain medications, although they may need to be
admitted to a treatment or recovery program and monitored closely if
controlled substances are prescribed for pain.
In the 1970s, news media reported the use of marijuana and heroin by
soldiers who were serving in Vietnam. Combat stress, the easy availability
of drugs, and the relaxation of taboos against drug use at the time all
contributed to the prob lem. Although many soldiers did have drug problems
while in Vietnam, 95 percent were not addicted to drugs after they returned
to the United States.12 This illustrates the profound effect that environmental
circumstances can have on drug taking and drug addiction.
In addition, scientists are working to identify genetic factors that contribute
to drug abuse and addiction. Studies of identical twins indicate that as much
as half of an individual’s risk of becoming addicted to nicotine, alcohol, or
other drugs depends on his or her genes. Recent technical advances in DNA
analysis have enabled researchers to untangle complex genetic interactions
by examining a person’s entire genome at once. A series of studies has
identified a certain variant in the gene for a nicotinic receptor subunit
that more than doubles the risk for addiction among smokers, as well as
increasing their vulnerability to lung cancer and peripheral arterial disease.
Animals as Research Models
Why do scientists study the brains of laboratory animals? Scientists use
ani mals in research studies because the use of humans is either impossible
or unethical. For example, when scientists investigate the effects of drugs
of abuse on brain function, either the question they are asking cannot be
answered in a living human or it would be inappropriate to give a person
the drugs.
The use of animals as subjects in scientific research has contributed to
many important advances in scientific and medical knowledge. Scientists
must ana lyze the goals of their experiments in order to select an animal
species that is appropriate. Scientists often use fruit flies ( Drosophila
melanogaster) when they want to learn more about genetics. However,
fruit flies are not a very good model if a scientist is investigating muscle
physiology or behavior; a mouse may be a better model for those
experiments. Although scientists strive to develop nonanimal models
for research, these models often do not duplicate the complex animal or
human body. Continued progress toward a more complete under standing
of human and animal health depends on the use of living animals.
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Guidelines for the Use of Animals in Scientific research
Scientists who use animals as research subjects must abide by federal policies that govern the use
and care of vertebrate animals in research. The Public Health Service established a policy that
dictates specific requirements for animal care and use in research. This policy conforms to the
Health Research Extension Act of 1985 (Public Law 99-158) and applies to all research, research
training, biological testing, and other activities that involve ani mals.13 The principles for using
and caring for vertebrate animals in research and testing are as follows:
• The transportation, care, and use of animals should be in accordance with the Animal Welfare
Act and other applicable federal laws, guidelines, and policies.
• Procedures involving animals should be designed with consideration of their relevance to
human or animal health, the advancement of knowledge, or the good of society.
• The animals selected should be of an appropriate species and quality and the minimum number
required to obtain valid results. Methods such as mathematical models, computer simulation,
and in vitro biological systems should be considered.
• Procedures should minimize discomfort, distress, and pain to the animals.
• Procedures that may cause more than momentary or slight pain should be performed with
appropriate sedation, analgesia, or anesthesia.
• Animals that would suffer severe or chronic pain or distress that cannot be relieved should be
painlessly killed.
• The living conditions of animals should be appropriate for the species. The housing, feeding,
and care of animals must be directed by a veterinarian or a trained, experienced scientist.
• Investigators who work with animals must be appropriately qualified and trained for
conducting procedures on living animals.
• Exceptions to any of these principles must be reviewed and approved by an appropriate
committee prior to the procedure.
• An Institutional Animal Care and Use Committee (IACUC) oversees all animal use in each
institution where ani mal research is conducted. The IACUC must give approval for the research
plan and species to be used. IACUCs include both scientists and nonscientists from outside the
institution. Nonscientists are often representa tives of humane organizations.
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Student Lesson 4
The Brain: Understanding Neurobiology Through the Study of Addiction
Web-Based Activities
In Advance
Activity
Web Component?
1
No
2
No
3
No
4
No
5
Yes
Photocopies
For the class
For each student
1 transparency of Master 4.4, 1 copy of Master 4.1, Data for Rat
Self-administration Experiment
1 transparency of Master 4.5, 1 copy of Master 4.2, Worksheet for
1 copy of Master 4.3, Evaluating
1 copy of Master 4.6, Long-Term
Effects of Drugs on the Brain (only
if not using the Web-based version)
Materials
Activity
Materials
Activity 1
none
Activity 2
colored pencils, overhead projector, transparency
playing cards (one deck for each group of
Activity 3
3 students; see Preparation section), overhead
projector
Activity 4
overhead projector
Activity 5
computer
Preparation
Gather decks of playing cards for use in Activity 3. Each group of three
students can share one deck of cards. Separate the face cards (jacks,
queens, and kings) and place them in one pile. Place the aces and number
cards in another pile.
Arrange for students to have access to computers for viewing the
minidocumentary online in Activity 5.
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Activity 1: How Does Drug Abuse Begin?
Procedure
1. Begin the activity by holding a class discussion. Ask students,
“What is a drug?” Write their answers on the chalkboard or on an
overhead trans parency. Give students the opportunity to present
differing views.
Content Standard F:
Students will respond with a variety of answers. Some will give
An individual’s mood
examples of illegal drugs, such as marijuana or cocaine, others may
and behavior may be
give the names of prescription medications. If so, prompt students
modified by substances.
to think about a definition for the word drug. Some students will
describe a drug either as an illegal substance that harms a person’s
health or as a chemical that a person takes to treat a disease or
illness. At this point, based on students’ knowledge, both
definitions are correct.
Several terms will be introduced in this lesson. It is very important
to use these terms according to the definitions provided.
2. Write the following definitions for drug and medication on the
board or transparency and inform students that, for this discussion,
you will use the terms according to the following definitions.
• A medication is a drug that is used to treat an illness or
disease accord ing to established medical guidelines.
• A drug is a chemical compound or substance that can alter
the structure and function of the body. Psychoactive drugs
affect the function of the brain, and some of these may be
illegal to use and possess.
3. If the students didn’t do this in the previous question, ask them
to con sider examples for both medications and drugs. List each
response in the proper category as a medication or a drug.
According to these definitions, all medications are drugs, but not all
drugs are medications. This module uses the word “drug” to refer to
psychoactive drugs, or drugs of abuse. Drug abuse refers to the use of
illicit drugs or to the inappropriate use of a legal drug or substance,
such as alcohol, nicotine, prescription drugs, or inhalants.
Societal and political factors sometimes influence into which category
a sub stance falls. Alcohol and nicotine (tobacco) are drugs that are
illegal to use and possess if the individual is below legal age, but not
for adults to possess and use responsibly. Also, inhalants (paints,
glues, and sprays, for example) are not illegal to possess when they
are used for their intended purposes. However, they are drugs when
used improperly to alter brain function.
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Student Lesson 4
The Brain: Understanding Neurobiology Through the Study of Addiction
Some students will raise the idea that medications can also be drugs
if they are used inappropriately. For example, overuse of a prescription
medication, such as a sedative, is inappropriate and wouldn’t be
considered a medication in that case. Alternatively, students may
indicate that morphine is an illegal drug when used without medical
supervision, but is a valuable medicine when used appropriately in a
hospital, or at home, to relieve pain associated with various diseases.
Students may also propose that marijuana can be a medica tion to
relieve the pain that accompanies various diseases. (In some states,
marijuana is legal as a medication, but is illegal according to federal
law.) If students bring this up, point out to them that scientists need
to continue studying marijuana or its active ingredients to determine
if it may be effective as a medicine. Mari juana contains hundreds of
chemical compounds; the effects of most of these compounds in the
body are unknown. Marijuana also poses many problems outside of
the brain—for the lungs, for example, because it is usually smoked.
Use this as an opportunity to inform students that scientific research
is being done to determine whether marijuana or other cannabinoid-
based medications are more effective than other medicines (see the
Back ground Information section).
4. Ask students to respond to the question, Why do people start
abusing drugs?
Students may provide a wide range of answers to this question
including peer pressure, experimentation, boredom, or fun. Some
students may also respond that people take drugs to escape from
life’s pressures.
Activity 2: Drug Abuse Is Voluntary; Addiction Is
Compulsive
Content Standard A:
1. For this activity, students will work in groups of four. Before you
Mathematics is essential
have stu dents divide into their small groups, set the stage for the
in scientific inquiry.
activity. Tell stu dents they will be analyzing data from experiments
Content Standard A:
using rats. For the experiments, each rat was placed in a cage with
Scientists rely on
two levers that the rat could press. If the rat pressed the food lever, a
pellet of food was released. If the stimulus lever was pressed, the rat
tech nology to enhance
received an injection or an electrical stimulus.
the gathering and
manipula tion of data.
Students may ask what substance was injected in response to the
Content Standard C:
press of the stimulus lever. Tell students that the answer to that
Organisms have
question will be revealed during the activity.
behav ioral responses
to inter nal changes
and to external stimuli.
Content Standard F:
An individual’s mood
and behavior may be
modified by substances.
100
Figure 4.3 Diagram of a rat in a cage during a
drug self-administration experiment.
2. Give each student a copy of Masters 4.1, Data for Rat Self
administration Experiment, and 4.2, Worksheet for Rat Experiment
Data. Each student will graph on Master 4.2 the data for only one of the rats. Instruct the teams to decide which member will graph
the data for Rats A, B, C, and D. The students will plot the total
number of times that the rat presses the stimulus lever vs. time and
the total number of times that the rat presses the food lever vs. time.
The graph of the data for each rat will have two lines, one for the
stimulus lever and one for the food lever. Students can use a different
color of pencil for plotting each set of data, or they can use a solid line
and a dashed line to distinguish between the two graph lines.
3. After students have completed their graphs, give each student a
copy of Master 4.3, Evaluating the Experiment. Each student should share his or her graph with the other members of the group. Group
members then discuss the similarities and differences among the rats’
responses and answer the questions on Master 4.3.
4. When the groups are finished answering the questions, hold
a class discussion to ensure that each group has come to the
appropriate conclusions.
Sample Answers to Questions on Master 4.3
Question 1. Why do the rats press a lever the first time?
The rats initially press a lever while they are exploring the cage.
A rat may even press the lever by accident. Whether a rat presses
the food lever or the stimulus lever first is usually random.
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The Brain: Understanding Neurobiology Through the Study of Addiction
Question 2. Compare the leverpressing behaviors of the four different
rats. Which rat pressed the stimulus lever the most? Which one pressed
the stimulus lever the least? Which rat pressed the food lever the most?
Which one pressed the food lever the least?
Rats A and C pressed the stimulus lever about the same number of
times and many more times than either Rat B or Rat D. Rats B and D
did not press the stimulus lever very many times, but they pressed the
food lever more times than Rats A and C did. Overall, Rats A and C
behaved similarly and Rats B and D behaved similarly.
Question 3. Rat A was injected with cocaine each time it pressed the
stimu lus lever. Can you use this fact to explain why Rat A behaved the
way it did?
The cocaine activated the reward system in the brain and caused the rat
to continue its stimulus-lever-pressing behavior. If necessary, remind
students that the reward system is the part of the brain stimulated by
drugs to cause feelings of pleasure.
Question 4. Based on the data you analyzed, do you think Rat B was
injected with cocaine when it pressed the stimulus lever? From what you
have learned so far in this unit, do you think Rat B was injected with a
different addictive drug when it pressed the stimulus lever? Why?
It appears that Rat B was not injected with cocaine when it pressed
the stimulus lever because its behavior was very different from Rat A.
If Rat B was injected with cocaine or another addictive drug, it should
display behavior similar to Rat A.
(Rat B actually received a saline injection when it pressed the
stimulus lever.)
Question 5. Do you think Rat C received cocaine when it pressed the
stim ulus lever? Why?
It is possible that Rat C received cocaine when it pressed the stimulus
lever because its behavior was very similar to that of Rat A. However,
you can not be sure that it was cocaine.
Question 6. Rat C did not receive an injection of cocaine when it pressed
the stimulus lever. When Rat C pressed the stimulus lever, it received a
mild electrical stimulation in the brain. On the basis of what you have
learned, can you predict what part of the brain was stimulated?
The reward system (ventral tegmental area or nucleus accumbens)
is the part of the brain stimulated. Stimulation in that area of the
brain caused the rat to continue pressing the stimulus lever.
102
Question 7. Rat D also received a mild electrical stimulation in the brain
when it pressed the stimulus lever. Do you think the same part of the
brain was stimulated in Rat D as was stimulated in Rat C? Why?
Rat D did not receive an electrical stimulation in the same part of the
brain that was stimulated in Rat C. If the same part of the brain, the
reward sys tem, was stimulated, Rat D should behave similarly to Rat C.
(Rat D received an electrical shock in the cerebellum, which is not part
of the reward pathway.)
Question 8. Why did Rats A and C press the stimulus lever more than
the food lever?
Rats A and C received a greater “reward” when they pressed the
stimulus lever than they did when they pressed the food lever.
Question 9. Why did Rats B and D press the food lever more than
the stim ulus lever?
Rats B and D received greater “reward” when they pressed the food
lever than they did when they pressed the stimulus lever.
Question 10. Why did the scientists who conducted this experiment
include Rats B, C, and D? How did the data from those rats help
scientists understand more about how cocaine acts in the brain?
Rats B, C, and D were used as controls in this experiment. Rat B
received a saline injection after pressing the stimulus lever. (The
cocaine that Rat A received was dissolved in a saline solution.)
Because Rat B’s behavior differed from Rat A’s beh