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Neuroendocrine Part III > Neurophysiology of Reward & Addiction > Flashcards

Neurophysiology of Reward & Addiction Flashcards

1
Q

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

A

-the difference bw the reward prediction and the actual reward

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2
Q

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

A

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

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3
Q

What happens to the RPE signals with repeated drug use?

A

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

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4
Q

Define motivation.

A

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

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5
Q

Define reinforcement.

A

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

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6
Q

Define saliency.

A

sthg important in the surrounding environment worth paying attention to

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7
Q

Define reward.

A

objects, stimuli, or activities that have positive value

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8
Q

Define aversion.

A

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

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9
Q

Define pleasure.

A

a positive sensation

aka euphoria or hedonia

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10
Q

What is the physiologic purpose of pleasure?

A

promote behaviors consistent w/ survival of self and species

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11
Q

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

A

increase

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

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12
Q

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

A

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

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13
Q

What is the brain pathway in the Basic circuit?

A

nucleus accumbens to prefrontal cortex

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14
Q

What is the function of the Basic circuit?

A

suppress sensations of pleasure and reward

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15
Q

Is the nucleus accumbens constantly in a state of activation?

A

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

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16
Q

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

A

GABA

-inhibitory

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17
Q

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

A

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

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18
Q

What is the brain pathway of the Reward Circuit?

A

ventral tegmental area to the nucleus accumbens

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19
Q

How does the ventral tegmental area get activated?

A
  • we engage in a rewarding activity
  • PFC releases EAA OR
  • other tegmental areas release Ach OR
  • hypothalamus releases orexin
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20
Q

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

A

-dopamine

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21
Q

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

A
  • 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
22
Q

What is the brain pathway for the Reward Feedback Circuit?

A

-nucleus accumbens BACK to the ventral tegmental area

23
Q

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

A

GABA

inhibitory

24
Q

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

A

dynorphin

endogenous opioid

25
Q

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

A

-kappa receptor

26
Q

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

A

suppresses further release of dopamine

27
Q

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

A

increases endogenous opioid signaling at all levels of the reward network

28
Q

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

A

activation of dopaminergic receptors

29
Q

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

A

-inhibit the GABA-releasing neurons

30
Q

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

A

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

31
Q

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?

A

dynorphin in the locus coeruleus

-where it mediates physical dependency

32
Q

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

A
  • short-lasting … only a few days

- CREB levels return to normal after drug cessation

33
Q

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

A

delta FosB

AP-1

34
Q

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

A
  • AMPA and NMDA receptors (for EAA’s)
  • elements of cell signal transduction pathways
  • factors promoting drug-seeking, motivation, and locomotion
35
Q

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

A

long-lasting

-months to years

36
Q

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

A
  • orbitofrontal cortex: impulsive behavior

- cingulate gyrus: regulates disinhibition

37
Q

Define conditioned associations.

A

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

38
Q

What part of the brain is responsible for conditioned associations?

A

hippocampus

39
Q

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

A

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

40
Q

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

A

low

-brain inhibits the drive to seek substances

41
Q

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

A

little to no effect

42
Q

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

A
  • high

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

43
Q

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

A

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

44
Q

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

A

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

45
Q

What activity does dopamine affect in the amygdala?

A

-increases retrieval of fear memories

46
Q

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

A

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

47
Q

What is the function of dopamine in the nucleus accumbens?

A

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

48
Q

What happens with dopamine in situations of acute stress?

A

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

49
Q

What happens neurophysiologically in situations of chronic stress?

A
  • 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
50
Q

What is the function of dopamine in the hippocampus?

A

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

51
Q

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

A

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

Neuroendocrine Part III (7 decks)

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