Lecture 7: Neurophysiology of Reward and Addiction

Question 1

What is motivation?

Answer 1

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

Question 2

What is saliency?

Answer 2

Something important in the surrounding env. worth paying attention to

Question 3

What is a reward?

Answer 3

Objects, stimuli, or activities that have positive value

Question 4

What is aversion?

Answer 4

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

Question 5

What is pleasure?

Answer 5

A positive sensation

Question 6

What is the purpose of pleasure?

Answer 6

Promote behaviors that are consistent with survival of self and the species

Question 7

What NT plays a role in pleasure reward seeking behavior?

Answer 7

Dopamine

Question 8

How do drugs affect dopamine concentration?

Answer 8

Will increase extracellular concentration of dopamine in limbic areas and prevent reuptake of dopamine

Question 9

What is a salience stimuli?

Answer 9

A noticeable stimuli that can be arousing or elicits a behavioral switch

Question 10

Why are addicts at a great risk for relapse when they visit places they had taken drugs at?

Answer 10

The stimuli around them are salient (noticeable)

The stimuli itself can increase dopamine and elicit desire for drugs.

Question 11

Briefly, how does the mesolimbic system work?

Answer 11

Dopamine is produced in VTA

VTA dopaminergic fibers are projected to nucleus accumbens.

Question 12

What is the main function of the nucleus accumbens?

Answer 12

Suppress sensations of pleasure and reward

Question 13

What structures constitutively activate (via EAA like glutamate) nucleus accumbens?

Answer 13

Hippocampus
Amygdala
Prefrontal cortex (PFC)

Question 14

What type of neurons does the nucleus accumbens release?

Answer 14

GABA (inhibitory)

Question 15

What pathway occurs when you do something that elicits a reward?

Answer 15

1. Dopamine neurons synthesized in VTA project to nucleus accumbens.
2. Dopamine released into NA, inhibits it.
3. NA activity decreases, resulting in a sensation of pleasure

Question 16

What stimulates the VTA when you engage in behavior or activity that results in rewards?

Answer 16

Pre-frontal cortex: EAA
Tegmental nuclei: ACh
Hypothalamus: Orexin (from food)

Question 17

What suppresses the VTA?

Answer 17

1. Nucleus Accumbens: GABA

2. Nucleus Accumbens: Dynorphin (transmitter)

Question 18

What is the dopamine-hypothesis reward?

Answer 18

Inactivation of nucleus accumbens via dopamine from VTA

Question 19

What activities can increase endogenous opioid signaling?

Answer 19

Exercise
Ethanol
Other stuff

Question 20

What receptors do opioid signaling utilize to activate dopaminergic receptors at VTA?

Answer 20

Mu receptors

Question 21

How does opioid signaling work?

Answer 21

1. Inhibit local VTA interneurons that normally suppress dopaminergic neurons in VTA
2. Disinhibit dopaminergic neurons
3. Activate nucleus accumbens local interneurons to inhibit the release of GABA
4. Activate pre-frontal cortex

Question 22

What is the result of endogenous opioid signaling?

Answer 22

Pleasure

Euphoria

Question 23

From a neurobiological perspective, what does addiction probably result from?

Answer 23

Recurrent supraphysiologic perturbations in dopamine system

Chronic drug exposure alters the morphology of neurons in dopamine-regulated circuits

Question 24

How can drugs change things at a cellular level?

Answer 24

Alter expression of certain transcription factors and proteins involved in neurotransmission in brain regions regulated by dopamine

Question 25

How can drugs change things at a neurotransmitter level?

Answer 25

Abnormal NT levels for dopamine, glutamate, GABA, opioids, serotonin

Question 26

Where are lasting memories of the good feelings associated with drugs created?

Answer 26

Memories made in hippocampus

Question 27

What structure mediates craving?

Answer 27

Amygdala

Question 28

When the abuser seeks out drugs, what structure is involved in the poor decision making?

Answer 28

Orbitofrontal cortex

Question 29

How does the activation of calcium-calmodulin-CREB mechanism work?

Answer 29

Promotes production of dynorphin in nucleus accumbens to shut off VTA and dopaminergic signaling

Question 30

What is physical dependency?

Answer 30

Chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms

Question 31

Why does physical dependency occur?

Answer 31

Excessive noradrenergic output from the locus ceruleus (involved in arousal and vigilance) CREB dependent up-regulation of target genes in locus ceruleus.

Question 32

When are the FosB and AP-1 genes up-regulated?

Answer 32

Stress | Drugs of Abuse

Question 33

How do natural reinforcers (food, sex, exercise) differ from drugs?

Answer 33

Natural Reinforcers: Firing of neurons stop when event concludes Drugs: Dopamine release continues after activity

Question 34

How does dopamine change the reward circuitry?

Answer 34

Dopamine can alter a fearful stimuli to a pleasurable one | Ex: Before hearing a bell could be scary, but now hearing a bell is associated with euphoria from drugs

Question 35

How do addicted brains differ from non-addicted brains?

Answer 35

Conditioned cues reinforce saliency of substances, increasing behavior to find and consume drugs. These cues override prefrontal cortex's control of behavior

Question 36

What role does the substantia nigra and dorsal striatum play in pleasure/reward-seeking behavior?

Answer 36

Control motor response associated with navigating the environment for desirable activity

Question 37

What are differences between conditioned responses and drug-associated cues?

Answer 37

Conditioned responses: cues to drug-taking in specific social circumstances Drug-associated cues: powerful cues that can elicit drug urges and physiologic responses w/o taking drug

Question 38

What role does the locus ceruleus play?

Answer 38

Involved with physiological responses to stress and panic | Synthesis of norepinephrine

Question 39

What does CREB mediate in the locus ceruleus?

Answer 39

Physical dependency due to excessive noradrenergic output from locus ceruleus