Journal Articles

Question 1

Salamone argues that the term “reward” is overused. What 3 definitions does he say the term can encompass?

Answer 1

Reinforcement
Primary motivation
Pleasure

Question 2

In terms of willingness to work for food reward, primary motivation to eat, and food-associated pleasure, which does Salamone say are controlled by nucleus accumbens dopamine?

Answer 2

Willingness to work for food reward

Question 3

Salamone article:
How did nucleus accumbens dopamine depletion affect:
1) Lever pressing for preferred food?
2) Eating standard food that did not require lever pressing?
3) Preference for preferred food vs standard food when no lever pressing was required?
4) What does this experiment tell us about the role of nucleus accumbens dopamine in food “reward”?

Answer 3

1) Decreased lever pressing for preferred food
2) More standard food eaten (animals ate standard food instead of lever pressing for preferred food)
3) Preference for preferred food was intact
4) Nucleus accumbens dopamine is necessary for willingness to work for preferred food, but not for primary motivation to eat or preference for preferred food

Question 4

Salamone article:
How did nucleus accumbens dopamine depletion affect:
1) Choice between arm of T maze with barrier and high amount of food and arm of T maze with no barrier and low amount of food?
2) Choice between arms of T maze (one low food, one high food) when no barriers were present?
3) What does this experiment tell us about the role of nucleus accumbens dopamine in food “reward”?

Answer 4

1) Chose arm of T maze with no barrier and low food
2) Chose arm of T maze with high food
3) Nucleus accumbens dopamine is necessary for willingness to work for reward, but not preference for reward

Question 5

Salamone article:

1) How is mesolimbic dopamine release affected by presentation of food reward itself?
2) How is mesolimbic dopamine release affected by presentation of stimulus associated with food reward?
3) What does this experiment tell us about the role of dopamine release in response to “reward”?

Answer 5

1) No increase
2) Increase
3) Dopamine release acts as a prediction signal for reward rather a direct response to reward itself

Question 6

Salamone article:

1) How does presentation of aversive stimuli (shock, tail pinch, stress, etc.) affect mesolimbic dopamine release?
2) How does dopamine antagonist treatment affect development of taste or place aversion?
3) What additional role of dopamine is understood through the results of these experiments? Does these results strengthen or weaken the argument of dopamine as a basis of reward? Why?

Answer 6

1) Increase mesolimbic dopamine release
2) Disrupts development of taste or place aversion
3) Dopamine as a mediator of aversive motivation
Weakens argument of dopamine as basis of reward- dopamine can play opposite role too

Question 7

How does Nutt define the dopamine theory in his article?

Answer 7

Dopamine release mediates reward and thus leads to addiction

Question 8

Nutt article:

1) How does the narcolepsy drug modafinil affect dopamine release?
2) Do people experience pleasure when taking modafinil as when taking drugs of abuse?
3) Does this strengthen or weaken the dopamine theory? Why?

Answer 8

1) Increases it
2) No
3) Weakens- shows that dopamine release doesn’t always result in “pleasure”

Question 9

Nutt article:

1) Describe how PET imaging was used to measure dopamine release in humans.
2) Overall, how was dopamine release affected by drug use in the studies Nutt reviewed?
3) What types of drugs led to the greatest changes in dopamine binding? The least?
4) What two drugs showed inconsistent results?
5) Does this strengthen or weaken the dopamine theory? Why?

Answer 9

1) Imaging of radiotracer that competes for D2/D3 dopamine receptors- decrease in radiotracer binding indicates an increase in dopamine
2) Increased
3) Greatest: stimulants (amphetamine)
Least: non-stimulants (THC, morphine)
4) Alcohol, nicotine
5) Weakens- shows that significant dopamine release doesn’t always occur with taking drugs of abuse

Question 10

Nutt article:

1) Describe how PET imaging was used to measure dopamine release in humans.
2) Describe how dopamine release was elicited in measurements of dopamine release.
3) For addicts of what types of drugs was dopamine release most blunted? Not blunted?
4) How was the addiction high risk group defined? Was dopamine release in this group blunted or not?
5) What does this tell us about blunting of dopamine release as a result of drug addiction?

Answer 10

1) Imaging of radiotracer that competes for D2/D3 dopamine receptors- decrease in radiotracer binding indicates an increase in dopamine
2) Treatment with a stimulant
3) Blunted- stimulants (cocaine), alcohol, opiate
Not blunted- cannabis
4) High familial risk of addiction and using stimulants occasionally, but not yet addicted
Dopamine release was blunted
5) Blunting of dopamine release doesn’t necessarily occur as a result of drug addiction

Question 11

Nutt article:

1) How is striatal dopamine receptor availability impacted differently for different drugs?
2) What does this tell us about striatal dopamine receptor availability changes as a result of drug addiction?

Answer 11

1) Decreased for stimulants (cocaine, methamphetamine) and alcohol, but not opiates or cannabis
2) Decrease in striatal dopamine receptors doesn’t necessarily occur as a result of drug addiction

Question 12

Nutt et al. theorize that dopamine has a greater role in addiction to what types of drugs? For other types of drugs, what other systems do Nutt et al. state are impacted?

Answer 12

Stimulants

GABA and endogenous opioid

Question 13

How do Morales et al. define dopamine neurons?

Answer 13

Synthesize and release dopamine

Question 14

Morales article:

1) Ventral tegmental area neurons can release what 3 neurotransmitters?
2) Do VTA neurons release one neurotransmitter per neuron, or can they release more than one? If more than one, give examples of combinatory neurons that exist in the VTA.

Answer 14

1) Dopamine, glutamate, GABA
2) Can release more than one neurotransmitter per neuron type
Combinatory neurons: dopamine/glutamate, dopamine/GABA, glutamate/GABA

Question 15

Morales article:

1) Dopamine neurons can contain what 3 proteins (think synthesis, cellular reuptake, and vesicular packaging)?
2) Do all VTA dopamine neurons contain all 3 proteins? If not, what does this reveal about dopamine neurons in the VTA?

Answer 15

1) Tyrosine hyrdoxylase (synthesis)
Dopamine transporter (DAT; cellular reuptake)
Vesicular monoamine transporter (VMAT; vesicular packaging)
2) No- can contain a combination of these 3 proteins
VTA dopamine neurons are molecularly heterogenous

Question 16

Morales article:

1) What two types of neurotransmitters are released into VTA? Give 2 examples of areas that release one of these neurotransmitters.
2) What neurotransmitters are released by the VTA? Give an example of an area and the neurotransmitters it receives.

Answer 16

1) GABA and glutamate
Medial prefrontal cortex releases glutamate into VTA
Nucleus accumbens releases GABA into VTA
2) Dopamine, GABA, glutamate
VTA releases dopamine, dopamine/glutamate, and GABA into nucleus accumbens

Question 17

Morales article:

1) What type of output from VTA has been implicated in reward and motivation (neurotransmitter, region that receives input from VTA)?
2) GABA and glutamate outputs from the VTA have been implicated in what two roles? What does this imply about the roles of GABA and glutamate in behavior?
3) What other type of outputs from VTA have been implicated in reward?
4) Does this strengthen or weaken the dopamine theory of reward? How?

Answer 17

1) Dopamine
Nucleus accumbens
2) Reward, aversion
GABA and glutamate have heterogenous roles
3) Combinatorial outputs
4) Weaken- dopamine isn’t the only neurotransmitter implicated in reward

Question 18

Nader article:

1) What are 2 benefits of measuring locomotor activity in animal models of drug addiction?
2) What is a limitation of using the locomotor activation paradigm?

Answer 18

1) Easy to measure
No training required
2) Doesn’t necessarily correlate with drug “reward”

Question 19

Nader article:

1) What is a benefit of the conditioned place preference paradigm? What is it useful for measuring?
2) What is a limitation of conditioned place preference?

Answer 19

1) Most drugs of abuse produce preference
Useful for measuring reward
2) Doesn’t measure drug seeking behavior

Question 20

Nader article:
Drug discrimination paradigm:
1) Describe the training procedure. How is this changed with drug vs control treatment?
2) What does this measure?
3) How can this be used to measure abuse liability for a new drug?
4) Limitation: what two variables can affect the results of drug discrimination?

Answer 20

1) Animal is trained to lever press in chamber with 2 levers- “correct” lever is paired with food reward
Different lever leads to food reward for drug treatment than for control treatment
2) Measures animal’s ability to know whether they have taken drug or not (“correct” lever press following drug administration shows that animal knows it has received drug)
3) Give animal new drug and see which lever it presses- if it presses “correct” lever for drug of abuse, it means that new drug has similar effects to drug of abuse
4) Starting dose
Environmental context (food restricted vs free feeding)

Question 21

Nader article:

What animal model of addiction does Nader argue best represents human condition of drug abuse?

Answer 21

Self-administration

Question 22

Nader article:

1) What is the difference between fixed ratio and progressive ratio in self-administration paradigm?
2) What are three limitations for self-administration (one drug-specific, one response rate for fixed ratio, one type of reinforcement)?

Answer 22

1) Fixed ratio- number of responses per drug presentation doesn’t change within test
Progressive ratio- number of responses per drug presentation increases each time
2) Animals won’t self-administer THC: not useful for understanding marijuana abuse
Number of responses in fixed ratio is more dependent on drug dose- response rate is low for too low and too high doses of drug
Doesn’t necessarily measure positive reinforcement- if animals are already drug exposed, could be trying to alleviate withdrawal effects

Question 23

How does Venniro define reinstatement?

Answer 23

Recovery of learned response following exposure to stimulus after period of extinction

Question 24

Venniro article:
How is reinstatement demonstrated in the following paradigms:
1) Self-administration? 
2) Runway?
3) Conditioned place preference?

Answer 24

1) Animal responds for drug following presentation of drug or other stimulus
2) Animal increases run time following presentation of drug or drug-associated cue
3) Animal shows preference for drug-paired side following presentation of drug or other stimulus

Question 25

Venniro article:
Explain how reinstatement is achieved with the following procedures:
1) Drug priming
2) Discrete cues
3) Discriminative cues
4) Contextual cues
5) Stress

Answer 25

1) Noncontingent (i.e. not dependent on animal’s behavior) presentation of drug triggers reinstatement
2) Drug-associated cue from conditioning phase triggers reinstatement
3) Drug-paired cue (as opposed to control-paired cue) from conditioning triggers reinstatement
4) Background cues paired with self-administration training trigger reinstatement
5) Exposure to stressors (i.e. lack of food, chemical stressor) triggers reinstatement

Question 26

Venniro article:
Explain the difference between the different abstinence models:
1) Forced abstinence
2) Voluntary abstinence induced by aversive consequences
3) Voluntary abstinence induced by alternate choice
4) What is measured after these abstinence models? How?

Answer 26

1) Animal is kept from drug self-administration not by its own choosing
2) Self-administration of drug is paired with aversive stimulus (i.e. shock), so animal stops using drug
3) Self-administration is interrupted by choosing to eat palatable food instead
4) Relapse
Presentation of drug or drug-associated cue -> measure lever presses