Neurophysiology of Reward & Addiction

Question 1

What do dopaminergic neurons detect in the reward and addiction pathways?

Answer 1

-the difference bw the reward prediction and the actual reward

Question 2

When do the DA nerons fire in the process of receiving natural rewards such as caring for young, palatable food, mating, and exercise?

Answer 2

-the reward prediction error (RPE) signals only continue until the predictions match the actual events

Question 3

What happens to the RPE signals with repeated drug use?

Answer 3

-repetition of the RPE signals continues … thus re-inforcing drug-related cues and behaviors

Question 4

Define motivation.

Answer 4

process that mediates goal-directed responses or goal-seeking behavior to changes in the external or internal environment

Question 5

Define reinforcement.

Answer 5

consequence of operant behaviors that alters the probability that a behavior will be repeated under similar conditions each time

Question 6

Define saliency.

Answer 6

sthg important in the surrounding environment worth paying attention to

Question 7

Define reward.

Answer 7

objects, stimuli, or activities that have positive value

Question 8

Define aversion.

Answer 8

a negative reinforcement of behavior that the individual will learn to avoid future encounters

Question 9

Define pleasure.

Answer 9

a positive sensation

aka euphoria or hedonia

Question 10

What is the physiologic purpose of pleasure?

Answer 10

promote behaviors consistent w/ survival of self and species

Question 11

How do drugs of abuse affect extracellular dopamine levels in limbic regions?

Answer 11

increase

-larger and longer increases than natural reinforcers such as food or sex

Question 12

Why are addicts at risk of relapsing when in an environment where they have previously used the drug?

Answer 12

increased salience caused by drug abuse causes the sensory stimuli associated w/ the drug to increase DA by themselves, which elicits a desire for the drug

Question 13

What is the brain pathway in the Basic circuit?

Answer 13

nucleus accumbens to prefrontal cortex

Question 14

What is the function of the Basic circuit?

Answer 14

suppress sensations of pleasure and reward

Question 15

Is the nucleus accumbens constantly in a state of activation?

Answer 15

-Yes, it receives a constant trickle of excitatory amino acids (ie glutamate) from the hippocampus, amygdala, and even the prefrontal cortex

Question 16

What neurotransmitter do the neurons of the nucleus accumbens release to the prefrontal cortex in the Basic circuit?

Answer 16

GABA

-inhibitory

Question 17

What does the release of GABA, an inhibitory neurotransmitter, mean for the pre-frontal cortex?

Answer 17

it’s under constant inhibition, in a “reward-neutral state”

Question 18

What is the brain pathway of the Reward Circuit?

Answer 18

ventral tegmental area to the nucleus accumbens

Question 19

How does the ventral tegmental area get activated?

Answer 19

• we engage in a rewarding activity
• PFC releases EAA OR
• other tegmental areas release Ach OR
• hypothalamus releases orexin

Question 20

What neurotransmitter do neurons from the ventral tegmental area release into the nucleus accumbens?

Answer 20

-dopamine

Question 21

What function does dopamine have on the neurons of the nucleus accumbens?

Answer 21

• dopamine inhibits the neurons of the NA and prevents them from doing their OWN inhibitory duties in the PFC
• results in a sensation of pleasure

Question 22

What is the brain pathway for the Reward Feedback Circuit?

Answer 22

-nucleus accumbens BACK to the ventral tegmental area

Question 23

What neurotransmitter is released from the nucleus accumbens into the ventral tegmental area?

Answer 23

GABA

inhibitory

Question 24

What co-transmitter is released along with GABA from the nucleus accumbens back into the ventral tegmental area?

Answer 24

dynorphin

endogenous opioid

Question 25

What receptor does dynorphin bind to in the ventral tegmental area?

Answer 25

-kappa receptor

Question 26

What is the action of dynorphin (from the nucleus accumbens) in the ventral tegmental area?

Answer 26

suppresses further release of dopamine

Question 27

How does exercise, ethanol, etc. initiate the dopamine-independent reward pathway?

Answer 27

increases endogenous opioid signaling at all levels of the reward network

Question 28

In the dopamine-independent reward pathway, what does the binding of endogenous opioids to mu receptors in the ventral tegmental area cause?

Answer 28

activation of dopaminergic receptors

Question 29

In the dopamine-independent reward pathway, what role do endogenous opioids have in the nucleus accumbens?

Answer 29

-inhibit the GABA-releasing neurons

Question 30

In the dopamine-independent reward pathway, what role do endogenous opioids have in the prefrontal cortex?

Answer 30

-they activate neurons and cause a profound sense of pleasure or euphoria

Question 31

Drug use alters the expression of CREB, a gene transcription factor that targets the location of which endogenous opioid in what area of the brain?

Answer 31

dynorphin in the locus coeruleus -where it mediates physical dependency

Question 32

Is the increase in CREB expression short-lasting or long-lasting?

Answer 32

- short-lasting ... only a few days | - CREB levels return to normal after drug cessation

Question 33

Besides CREB, what are other transcription factors whose levels are altered by drug abuse?

Answer 33

delta FosB | AP-1

Question 34

What is upregulated by the increase in delta FosB and AP-1?

Answer 34

- AMPA and NMDA receptors (for EAA's) - elements of cell signal transduction pathways - factors promoting drug-seeking, motivation, and locomotion

Question 35

Are the changes caused by an increase in delta FosB and AP-1 long-lasting or short-lasting?

Answer 35

long-lasting | -months to years

Question 36

What areas of the mesocortical region and their associated functions are affected by increased levels of neurotransmitters found there in the brains of addicts?

Answer 36

- orbitofrontal cortex: impulsive behavior | - cingulate gyrus: regulates disinhibition

Question 37

Define conditioned associations.

Answer 37

-memories that associate the good feelings of drugs w/ the circumstances and environments in which they occur

Question 38

What part of the brain is responsible for conditioned associations?

Answer 38

hippocampus

Question 39

The associative learning (conditioning) induced by large increases in dopamine from drug use causes what?

Answer 39

-phasic firing of dopamine neurons in the ventral tegmental area, resulting in the expectation of reward

Question 40

What is the level of saliency of substances and substance cues in the brain of a non-addict?

Answer 40

low -brain inhibits the drive to seek substances

Question 41

What effect do conditioned cues have on the saliency of substances in the brain of a non-addict?

Answer 41

little to no effect

Question 42

What is the level of saliency of substances and substance cues in the brain of an addict?

Answer 42

- high | - overrides the PFC's control of behavior; PFC can no longer inhibit the drive to seek substances

Question 43

What effect to conditioned cues have on the saliency of substances in the brain of an addict?

Answer 43

-conditioned cues re-inforce the saliency and further increase substance-seeking behavior

Question 44

How does the saliency of drugs compare to the salience of natural rewards?

Answer 44

saliency of substances overrides the saliency of natural rewards, which no longer influence behavior

Question 45

What activity does dopamine affect in the amygdala?

Answer 45

-increases retrieval of fear memories

Question 46

What is the function of dopamine in the ventral tegmental area?

Answer 46

-it signals the prediction error bw the expected outcome and the actual reward experienced

Question 47

What is the function of dopamine in the nucleus accumbens?

Answer 47

assignment of salience to certain stimuli and mediate decisions that seek (or avoid) a desirable (or aversive) situation

Question 48

What happens with dopamine in situations of acute stress?

Answer 48

-corticotrophan releasing factor (CRF) increases dopamine release in the nucleus accumbens in the short-term to help us power through stressful situations

Question 49

What happens neurophysiologically in situations of chronic stress?

Answer 49

- reward system is dampened - things that used to stimulate reward aren't valuable anymore - great reward is needed until eventually it doesn't work at all

Question 50

What is the function of dopamine in the hippocampus?

Answer 50

-provides place and direction-contextual information about environment in which stimuli are experienced

Question 51

What is the function of dopamine in the substantia nigra and dorsal striatum?

Answer 51

-motor response associated w/ navigating the environment toward a desirable cue w/ goal of engaging in the activity that elicits reward