Neurophys. of Reward and Addiction

Question 1

A process that mediates goal-directed responses or behavior to changes in environment

Answer 1

Motivation

Question 2

Consequence of learned behaviors that alters probability that a behavior will be repeated again

Answer 2

Reinforcement

Question 3

What is salience?

Answer 3

Wanting; something important in the environment worth paying attention to

Question 4

“Something having salience”

Answer 4

Something has value to the individual so that they want it

Question 5

What can trigger salience?

Answer 5

Encounters with reward/related cues; experienced as surges of motivation to obtain the reward

Question 6

3 things that reward involves?

Answer 6

1. Hedonic effect of pleasure
2. Salience (motivation to obtain reward due to its value)
3. Associated learning

Question 7

Negative reinforcement of behavior that the person will learn to avoid in future encounters

Answer 7

Aversion

Question 8

No longer liking something previously liked; lack of interest

Answer 8

Anhedonia

Question 9

Hedonia

Answer 9

Pleasure or liking

Question 10

Physiologic purpose of pleasure is to?

Answer 10

Promote behaviors that are consistent with survival of self and species

Question 11

What neurons encode the DISCREPANCY between reward prediction and info about the actual reward received?

Answer 11

Dopaminergic

Question 12

As dopaminergic neurons encode the discrepancy between reward prediction and actual reward, they broadcast the signal downstream. Why?

Answer 12

So you LEARN exactly what is rewarding and what is NOT

Question 13

Mismatch between events and reward elicited

Answer 13

Reward prediction error (RPE)

Question 14

What does an unpredicted reward elicit?

Answer 14

Activation (positive prediction error)

Question 15

What does a fully predicted reward elicit?

Answer 15

No response

Question 16

What does the omission of a predicted reward induce?

Answer 16

Depression (negative prediction error)

Question 17

Repeated drug use does what to the RPE?

Answer 17

Repetition of the RPE signals continues to reinforce the drug behavior

Question 18

Natural rewards do what to the RPE?

Answer 18

Produce error-correcting dopaminergic RPE signals until the predictions match actual events

Question 19

Drugs of abuse increase extracellular _____ concentrations

Answer 19

Dopamine

Question 20

Drugs of abuse increase dopamine, where?

Answer 20

Limbic regions and nucleus accumbens

Question 21

Compared to natural reinforcers such as food and sex, drugs of abuse provide what type of increase in dopamine?

Answer 21

5-10 fold increases in dopamine that last longer as well than normal reinforcers

Question 22

Cocaine, meth, ecstasy and others increase dopamine _____

Answer 22

Directly

Question 23

Alcohol, nicotine, marijuana increase dopamine _____

Answer 23

Indirectly

Question 24

What are the main structures involved in reward pathways?

Answer 24

Nucleus Accumbens
Ventral Tegmental Area
Prefrontal Cortex
Limbic System

Question 25

Normal function of Nucleus Accumbens?

Answer 25

SUPPRESS sensations of pleasure/reward

Question 26

Nucleus Accumbens neurons are consistently activated by what areas of the brain and by what NT?

Answer 26

PFC, Amygdala, Hippocampus all release EAA (glutamate) and activate Nucleus Accumbens neurons

Question 27

When the Nucleus Accumbens is working under normal conditions, what is the pathway?

Answer 27

Nucleus accumbens neurons receive EAA and are stimulated - They project to the Pre-frontal cortex - They release GABA and inhibit the neurons there == results in NO pleasure sensed (neutral state)

Question 28

What type of neurons are Nucleus Accumbens neurons?

Answer 28

GABAergic

Question 29

Under normal conditions, Nucleus Accumbens neurons inhibit what area of the brain?

Answer 29

Pre-frontal cortex

Question 30

The reward circuit is also known as?

Answer 30

Dopamine Hypothesis of Reward

Question 31

Drugs can activate what pathway?

Answer 31

Dopamine Hypothesis of Reward

Question 32

For the reward circuit, what areas of the brain help to activate the Ventral Tegmental Area neurons?

Answer 32

Prefrontal cortex Dorsal Tegmental Area Hypothalamus

Question 33

For the reward circuit, what does the prefrontal cortex release to dopaminergic neurons in the VTA?

Answer 33

EAA

Question 34

For the reward circuit, what does the Dorsal Tegmental area release to dopaminergic neurons in the VTA?

Answer 34

Acetylcholine

Question 35

For the reward circuit, what does the Hypothalamus release to dopaminergic neurons in the VTA?

Answer 35

Orexin

Question 36

Once the Ventral Tegmental Area is activated, it projects neurons that release _____ to the nucleus accumbens

Answer 36

Dopamine

Question 37

Dopamine at the nucleus accumbens does what to its neurons?

Answer 37

Inhibit them from releasing GABA

Question 38

Once dopamine inactivates the nucleus accumbens neurons, what is the result?

Answer 38

Sensation of pleasure

Question 39

How is the dopamine hypothesis of reward circuit turned off?

Answer 39

Nucleus accumbens neurons project back to the Ventral Tegmental area - They release GABA AND DYNORPHIN - This halts the release of dopamine and halts reward process

Question 40

What receptor does dynorphin use at the Ventral tegmental area to turn off reward signaling?

Answer 40

Kappa - opioid receptor

Question 41

What are some things that can stimulate the dopamine-independent reward pathway?

Answer 41

Exercise, ethanol and other activities

Question 42

What type of receptors are activated with the dopamine- independent reward pathway?

Answer 42

Mu - opioid receptors

Question 43

What 3 things does the dopamine-independent pathway have to activate to get the result of sensing pleasure?

Answer 43

1. Inhibits the inhibiting interneurons in the VTA that normally suppress dopaminergic activity 2. Local interneurons in the NA to inhibit the GABAergic neurons 3. PFC itself

Question 44

What area of the brain associates rewarding feelings with the circumstance/environment they occurred?

Answer 44

Hippocampus

Question 45

What area of the brain mediates craving?

Answer 45

Amygdala

Question 46

What area of the brain controls when an abuser encounters associated person/things they are driven to make poor decisions?

Answer 46

Orbitofrontal cortex

Question 47

What do memory mechanisms act on to induce learning?

Answer 47

Dynorphin and ion channels that control excitability of Nucleus Accumbens

Question 48

Short term learning and memory mechanism

Answer 48

Increased phosphorylation of AMPA receptor in post-synaptic cell

Question 49

Longer term learning and memory mechanism

Answer 49

Activation of Calcium-calmodulin-CREB mechanism

Question 50

Life long learning and memory mechanism

Answer 50

Cascades involved deltaFosB and AP-1

Question 51

Describe the CREB pathway in the Nucleus Accumbens

Answer 51

Calcium binds calmodulin - Activates cAMP to activate PKA - - Activates CREB to alter gene expression of Dynorphin

Question 52

Describe the CREB pathway in the Locus Ceruleus

Answer 52

Same as the Nucleus Accumbens pathway for CREB, Locus ceruleus mediates physical dependency

Question 53

Drugs of abuse, chronic stress, etc. activate what transcription factors for life long memories?

Answer 53

DeltaFosB and AP-1 to induce drug seeking and motivation and locomotion

Question 54

2 ways Dopamine can alter fear conditioning

Answer 54

1. Alter association itself | 2. Alter expression of memory

Question 55

What area of the brain can assign salience to a stimuli and mediate decisions to seek or avoid?

Answer 55

Nucleus Accumbens

Question 56

Corticotroph Releasing Factor (CRF) increases dopamine in the NA due to what?

Answer 56

Acute (short term) stress

Question 57

Corticotroph Releasing Factor (CRF) induces dopamine release that was once associated with pleasurable results to now to aversive results due to what?

Answer 57

Chronic (long term) stress

Question 58

Retrieval of fear memories

Answer 58

Amygdala

Question 59

Motor response associated with engaging in activity that elicits reward

Answer 59

Substantia nigra and dorsal striatum

Question 60

Provides spatial info about environment in which stimuli is experienced

Answer 60

Hippocampus

Question 61

Signals prediction error between expected outcome and actual reward

Answer 61

Ventral Tegmental Area