10.1 Neurophysiology of Reward and Addiction

Question 1

Motivation is a process that mediates goal-directed responses or goal-seeking behavior to changes in the _______ or _______ _______.

Answer 1

external; internal environment

Question 2

Reinforcement is the consequence of operant/learned behaviors that ______ ____ ______ that a behavior will be ______ under similar conditions each time.

Answer 2

alters the probability; repeated

Question 3

Saliency is something important in the _____ ______ worth paying attention to.

Answer 3

surrounding environment

Question 4

What is a reward?

Answer 4

Objects, stimuli, or activities that have positive value.

Question 5

Aversion is a ______ reinforcement of behavior that the individual will learn to ____ in future encounters.

Answer 5

negative; avoid

Question 6

Pleasure is a _____ sensation often referred to as ______ or ______.

Answer 6

positive; eupohore; hedonia

Question 7

The physiologic purpose of pleasure is to promote behaviors that are consistent with _____ __ ____ and the _____.

Answer 7

survival of self; species

Question 8

What are natural rewards elicited by?

Answer 8

caring for young, palatable food, mating, and exercise

Question 9

______ neurons encode the discrepancy between reward predictions and information about the actual reward received and broadcast the signal downstream to reward centers in the brain.

Answer 9

Dopaminergic

Question 10

An unpredicted reward elicits an activation called a ______ ______ ______.

Answer 10

positive prediction error

Question 11

A fully predicted reward elicits _____ _____.

Answer 11

no response

Question 12

Omission of a predicted reward elicits a ______.

Answer 12

depression

Question 13

Over repeated drug use, the repetition of reward prediction error (RPE) signals would ______ drug-related cues and behaviors.

Answer 13

reinforce

Question 14

_______ _______ produce error-correcting DA-RPE signals only until the predictions match the actual events.

Answer 14

Natural rewards

Question 15

_______ is associated with the reinforcing effects of most drugs of abuse.

Answer 15

Dopamine

Question 16

Drugs of abuse increase _______ _______ concentrations in limbic regions, including the nucleus accumbens.

Answer 16

extracellular dopamine

Question 17

Drugs of abuse provide _____ and _____ increases in dopamine than natural reinforces such as food and sex.

Answer 17

longer; larger

Question 18

Which drugs increase dopamine directly?

Answer 18

cocaine, amphetamine, methamphetamine, and ecstasy

Question 19

Which drugs increase dopamine indirectly via other neuron receptors?

Answer 19

nicotine, alcohol, opiates, and marijuana

Question 20

Salience refers to a stimuli or environmental changes that are ______ or elicit an ______-______ switch.

Answer 20

arousing; attentional-behavioral

Question 21

Salience affects the ______ to seek an anticipated reward and facilitates _____ _____.

Answer 21

motivation; conditioned learning

Question 22

Because dopamine is involved in the _____ of reward and ______, drug-induced increases in dopamine will inherently motivate further procurement of more drug, regardless or whether or not the effects of the drug are perceived as pleasurable.

Answer 22

prediction; salience

Question 23

Salience leads to a situation in which _____ _____ associated with the drug can increase dopamine themselves and elicit the desire for the drug.

Answer 23

sensory stimuli

Question 24

What does the mesolimbic system consist of?

Answer 24

nucleus accumbens, ventral tegmental area (VTA), limbic system, and pre-frontal cortex

Question 25

What are the important neurotransmitters in the mesolimbic system?

Answer 25

dopamine, GABA, opioids, EAAs, dynorphin, and orexin

Question 26

The main function of the nucleus accumbens is to _____ sensations of pleasure/reward.

Answer 26

suppress

Question 27

The nucleus accumbens is _______ ______ by a constant trickle of EAAs like glutamate.

Answer 27

constitutively activated

Question 28

The nucleus accumbens neurons are GABAergic meaning the activation of these neurons stimulate them to _____ _____.

Answer 28

release GABA

Question 29

GABA is _____, so stimulation of nucleus accumbens neurons will _____ their target.

Answer 29

inhibitory; inhibit

Question 30

Constitutive inhibition of the pre-frontal cortex targets keeps the brain in a ______-_____ state.

Answer 30

reward-neutral

Question 31

When you do something that elicits a reward, the _____ becomes activated.

Answer 31

ventral tegmental area (VTA)

Question 32

Dopaminergic neurons from the VTA project to the _____ _____.

Answer 32

nucleus accumbens

Question 33

Ultimately, when you do something that elicits a reward, the nucleus accumbens activity (releasing GABA & suppressing sensations of pleasure) is _____.

Answer 33

inhibited

Question 34

Decreased nucleus accumbens activity (decreased GABA release) results in _______ ____ _______.

Answer 34

sensation of pleasure

Question 35

The VTA is activated by ____, ____, or _____.

Answer 35

EAAs (glutamate); orexin; acetylcholine

Question 36

The pre-frontal cortex releases ______.

Answer 36

EAAs (glutamate)

Question 37

The dorsal tegmental area releases ______.

Answer 37

acetylcholine

Question 38

The hypothalamus releases _____ and is activated by ______ ___ ____.

Answer 38

orexin; consumption of food

Question 39

Nucleus accumbens neurons release ____ and _______.

Answer 39

GABA and dynorphin

Question 40

Dynorphin is an _____ that binds to the ____-____ receptor in the VTA.

Answer 40

opioid; kappa-opioid

Question 41

Together, GABA and dynorphin _____ the additional release of dopamine from the VTA as a means to ____ the reward process.

Answer 41

suppress; halt

Question 42

The inactivation of the nucleus accumbens via dopaminergic neurons from the VTA is termed the ________-________ ____ ______.

Answer 42

dopamine-hypothesis of reward

Question 43

Many drugs of abuse activate the ______ __-_____.

Answer 43

mesolimbic DA-system

Question 44

Endogenous opioids activate the _____-_______ reward pathway.

Answer 44

dopamine-independent

Question 45

Exercise, ethanol, and other activities increase endogenous opioid signaling at the ____, _____, and _____.

Answer 45

VTA; nucleus accumbens; pre-frontal cortex

Question 46

Opioids activate ___-receptors which activate dopaminergic neurons in the VTA (via inhibiting local VTA interneurons which normally suppress dopaminergic activity), activate local interneurons in the nucleus accumbens (via inhibiting GABA-ergic neurons), and activate the pre-frontal cortex.

Answer 46

mu

Question 47

Opioids _____ dopaminergic neurons in the VTA, allowing ______ dopamine in the nucleus accumbens, inhibiting GABA release, resulting in a profound sense of _____ via activation of the PFC.

Answer 47

disinhibit/activate; increased; pleasure

Question 48

Compared to normal reward stimuli, rewards due to drugs of abuse are ______ to an otherwise mild stimulus because the dopamine signal in the nucleus accumbens is not proportional to the stimulus.

Answer 48

exaggerated

Question 49

Chronic drug exposure alters the ______ of neurons in dopamine-related circuits.

Answer 49

morphology

Question 50

Drugs have been reported to alter the expression of certain ______ _____ as well as a variety of proteins involved in neurotransmission.

Answer 50

transcription factors

Question 51

What neurotransmitters have been documented to have addiction-related adaptations?

Answer 51

Dopamine, glutamate, GABA, opioids, serotonin, and various neuropeptides.

Question 52

In people with addictions, abnormal neurotransmitter levels are found in the ________ region of the brain.

Answer 52

mesocortical

Question 53

What does the mesocortical region of the brain include?

Answer 53

orbitofrontal cortex and cingulate cortex

Question 54

The orbitofrontal cortex is involved in _____ _____.

Answer 54

compulsive behavior

Question 55

The cingulate gyrus regulates ________.

Answer 55

disinhibition

Question 56

What are conditioned associations?

Answer 56

A lasting memory that is created which associates good feelings with the circumstance and environment in which they occur.

Question 57

Conditioned associations occur in the ______ and utilize circuitry which mediates _____ in the ______ when the abuser encounters the persons or things and is then driven to make poor decisions or seek out more drugs in spite of obstacles.

Answer 57

hippocampus; cravings; amygdala

Question 58

Dynorphin feeds back from nucleus accumbens and helps to _____ dopaminergic signaling from the VTA.

Answer 58

suppress

Question 59

The locus coeruleus is involved in _____ and ______.

Answer 59

arousal; vigilance

Question 60

_____ ______ is due to excessive noradrenergic output from the locus coeruleus and CREB-dependent upregulation of target genes (dynorphin) in the locus coeruleus.

Answer 60

Physical dependency

Question 61

DeltaFosB and AP-1 are upregulated by ____ and ____ ___ ____.

Answer 61

stress; drugs of abuse

Question 62

______ and ____ upregulate expression of EAA receptor expression, elements of cell signal transduction pathways, and factors promoting drug seeking, motivation, and locomotion.

Answer 62

DeltaFosB and AP-1

Question 63

Eventually, becoming _______ to fear drug withdrawal effects (which can be relieved by taking the drug) might lead to any source of stress or frustration becoming a ___ for drug use.

Answer 63

conditioned; cue

Question 64

____ ______ is learning that one behavior is associated or leads to something unpleasant or aversive.

Answer 64

Fear conditioning

Question 65

________ release within the reward circuit alters the subjective value assigned to fearful stimuli and directly affects memory consolidation.

Answer 65

Dopamine

Question 66

Dopamine can alter the _____ through which fear occurs, alter the _____ itself, and/or alter the expression of the ______.

Answer 66

conditions; association; memory

Question 67

In a non-addicted brain, the saliency of substances and substance cues should be ___.

Answer 67

low

Question 68

In a non-addicted brain, conditioned cues have _____ to ____ influence on the saliency of drug-substances.

Answer 68

little; no

Question 69

In a non-addicted brain, the saliency of natural rewards greatly ______ the saliency of drugs.

Answer 69

overrides

Question 70

In an addicted brain, the saliency of substances and substance-related cues is _____.

Answer 70

increased

Question 71

In an addicted brain, the pre-frontal cortex ____ _____ the drive to seek substances.

Answer 71

cannot inhibit

Question 72

In an addicted brain, conditioned cues _____ the saliency of substances, further increasing _______-_______ behavior.

Answer 72

reinforce; substance-seeking

Question 73

In an addicted brain, the saliency of substances ______ the saliency of natural rewards (which __ _____ influence behavior).

Answer 73

overrides; no longer

Question 74

What does dopamine modulate in the amygdala?

Answer 74

retrieval of fear memories

Question 75

Dopamine in the ______ signals prediction error between expected outcome and actual reward.

Answer 75

VTA

Question 76

Dopamine in the ______ ______ modulates assignment of salience to certain stimuli and mediate decisions that seek (or avoid) a desirable (or aversive) situation.

Answer 76

nucleus accumbens

Question 77

Acute stress (______ ______ ______) usually increases dopamine release in the nucleus accumbens in the short term.

Answer 77

corticotropin releasing factor (CRF)

Question 78

______, ______, ______ stress results in CRF inducing a dopamine release. This causes dopamine to now be associated with ______ rather than pleasurable, appetitive results. This switches the _____ _____ to acute stressors.

Answer 78

prolonged; chronic; severe; aversion; emotional response

Question 79

The _______ provides place and direction-contextual information about the environment in which stimuli are experienced.

Answer 79

hippocampus

Question 80

Dopamine in the _____ _____ and _____ _____ causes a motor response associated with navigating the environment toward a desirable cue with the goal of engaging in the activity that elicits rewards.

Answer 80

substantia nigra; dorsal striatum

Question 81

____-____ _______ is a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse.

Answer 81

long-term potentiation

Question 82

In the ____ term, increased phosphorylation of ____ receptors and insertion of additional those receptors into the post-synaptic membrane of the locus coeruleus causes physical dependency.

Answer 82

short; AMPA

Question 83

In the ____ term, ____-dependent upregulation of target genes involved in learning and memory causes physical dependency.

Answer 83

long; CREB

Question 84

Activation of the calcium-calmodulin-CREB mechanism causes _______ _______ in the ____ term.

Answer 84

physical dependency; long