Animal Models of Drug Abuse

Question 1

What is reinforcement, and what paradigm measures this in animal models?

Answer 1

Something that changes a pattern of behavior (i.e. a reward)

Conditioned place preference

Question 2

Can reward and pleasure be directly measured in animal models? Why or why not? If not, how are these concepts measured?

Answer 2

No- they are complex, subjective experiences

Measured indirectly through animal’s behavior

Question 3

What type of a setup is used for the conditioned place preference test? What are the different chambers?

Answer 3

2- chamber apparatus with small middle chamber in between

Neutral chamber and drug-associated chamber

Question 4

Describe the procedure for the conditioned place preference test. What happens before testing? What happens during testing? What result shows rewarding properties of drug?

Answer 4

Before testing: animal is given drug in drug-associated chamber
During testing: animal is placed in middle chamber and gets to choose between going to neutral and drug-associated chambers
Rewarding properties of drug are shown if animal spends more time in drug-associated chamber

Question 5

Conditioned place preference: if drug has rewarding properties, than what happens to drug-associated chamber?

Answer 5

Drug-associated chamber becomes rewarding as well

Question 6

What is measured before giving the animal any drug or assigning a biased or unbiased approach to conditioned place preference test? What is the difference between biased and unbiased approach in conditioned place preference test?

Answer 6

Which chamber the animal naturally gravitates toward
Biased: the less favored chamber becomes the drug-associated chamber
Unbiased: drug-associated chamber is picked randomly

Question 7

How can an unbiased or biased approach to conditioned place preference affect the results, as seen in a study with nicotine?

Answer 7

Unbiased approach: animals showed no preference for nicotine
Biased approach: animals showed preference for nicotine when it was paired with the least preferred side

Question 8

Prior to the conditioned place preference test, does an animal’s preference for one chamber over the other change over time? What does that mean for the results of drug administration?

Answer 8

No
If animal comes to prefer other chamber as a result of drug administration, it shows that the animal finds the drug rewarding

Question 9

How many pairings are needed to create conditioned place preference for heroin? Sex? What does this imply for the rewarding properties of drugs vs naturally occurring rewards/behaviors?

Answer 9

1 pairing for heroin
5 pairings for sex
Drugs are more rewarding than naturally occurring behaviors/rewards

Question 10

What happens to the amount of time an animal spends in the drug-associated chamber as the dosage of drug given increases?

Answer 10

Increases to a point, then decreases as dose continues to increase

Question 11

Can the conditioned place preference test results be tied completely to reward? Why or why not? What else might be measured?

Answer 11

No- learning and memory are also measured in this paradigm

Question 12

What happened in the experiment where animals were tested in the conditioned place preference paradigm after not having had cocaine for 6 weeks? What does this result show?

Answer 12

Animals still showed preference for drug-associated chamber

Drug administration created a long-term association

Question 13

How does extinction work in the conditioned place preference test? What happens to chamber preference after extinction?

Answer 13

Animals are put back in drug-associated chamber, but not given drug
Animals show less preference for drug-associated chamber than before

Question 14

How does reinstatement work after extinction in the conditioned place preference test? What happens to chamber preference after reinstatement? What does this show about the effects of abstinence in addiction treatment?

Answer 14

Animals are given drug again, then given the option to roam between chambers
Animals show preference for drug-associated chamber again
Abstinence doesn’t cure addiction- rewarding effects and associations can be reinstated when taking drug again

Question 15

Does reinstatement in the conditioned place preference test only work with the same drug that was originally tested with?

Answer 15

No- different drugs can trigger drug-associated chamber preference

Question 16

What is tolerance? Does it cause drug seeking behavior?

Answer 16

Diminished response to a drug following repeated usage (i.e. need more of drug to get same effect)
Tolerance doesn’t cause drug-seeking behavior

Question 17

What effect do drugs of abuse have on behavioral activity? This effect is a manifestation of what property of drugs? How does this property affect further drug use?

Answer 17

Increases behavioral activity
Sensitization
Increases further drug use

Question 18

What test is used to measure drug sensitization in animals? How does it work?

Answer 18

Locomotor sensitization

Inject animal with drug, then measure its activity

Question 19

In the locomotor sensitization test, what happens to the animal’s activity over time with the same dose of drug?

Answer 19

Animal’s activity increases

Question 20

What happened to the animals’ activity in the locomotor sensitization experiment when animals were given amphetamine 28 days after their last injection? How did this result compare to the animals that had shorter abstinence periods? What does this result suggest for the effects of abstinence on sensitization?

Answer 20

Activity increased
Greater increase than for animals with shorter abstinence periods
Abstinence increases sensitization rather than diminishing it

Question 21

Amphetamine-treated rats still showed increased activity in the locomotor sensitization test even after how long? About what percentage of the rat’s life is this length of time? What does this result suggest about abstinence as a treatment for addiction?

Answer 21

1 year
About a third
Not very effective

Question 22

How is voluntary use of drugs modeled in animals? How does this test work?

Answer 22

Drug self-administration test

Animal presses a bar, it receives a dose of drug

Question 23

Do rodents generally start out the drug self-administration test being trained to take the drug of interest? Why or why not? If not, what is used first?

Answer 23

No- animals don’t voluntarily take drug at first

Must be trained with food first, which is gradually replaced with drug

Question 24

In the drug self-administration test, how does the rate of cocaine administration in mice change over time? What does this tell us about what the animals are trying to achieve? Do these animals self-administer until they pass out or die?

Answer 24

At first, increase administration, but once a certain dose is reached, self-administration sharply drops
Animals are trying to achieve desired “high” effect
Animals don’t self-administer until they pass out or die

Question 25

If animals don’t self-administer until they pass out or die, then why do humans overdose on drugs?

Answer 25

Humans might not know the potency of the drug they are taking (street drugs can be adulterated), so they might take more than they intended to

Question 26

How does drug self-administration in animals differ between short and long access periods? What is the long access period supposed to model?

Answer 26

Animals take more drug over long access periods

Compulsive drug taking

Question 27

What happened to drug administration after a period of abstinence for the animals in the short vs long access period groups in the drug self-administration test? For the long access group, was the amount of drug taken higher or lower than before abstinence? What does this suggest about the effects of abstinence on compulsive drug seeking?

Answer 27

Short access group maintained steady dosage, whereas long access group greatly increased drug use over time and increased drug use over what was taken before period of abstinence
Abstinence increases compulsive drug seeking rather than diminishes it

Question 28

How is break point measured in drug self-administration tests? Are the break points for food and cocaine similar or different in animals? How is that different than for people?

Answer 28

Gradually increasing the number of times animal must press bar for reward- eventually, animal decides that it isn’t worth it
Similar for food and cocaine
People often find drugs more rewarding than food