Neurophysiology Of Reward And Addiction

Question 1

Motivation

Answer 1

Process that mediates goal-directed responses or goal-seeking behavior changes in external or internal environment

Question 2

Saliency

Answer 2

Something important in surrounding environment worth paying attention to

Question 3

Reward

Answer 3

Objects, stimuli, or activities that have positive value

Question 4

Aversion

Answer 4

Negative reinforcement of behavior that will cause avoidance in future

Question 5

Physiologic purpose of pleasure

Answer 5

To promote behaviors consistent with survival of self and species

Question 6

Dopamine and Drug Abuse

Answer 6

Drugs of abuse increase extracellular [dopamine] in Limbic regions including NA
-they produce longer and larger increases than natural reinforces
—cocaine, amphetimine increase dopamine directly, while nicotine and alcohol work indirectly

Question 7

Dopamines affect on prediction of reward

Answer 7

Dopamine release influences the salience of drug use, so this will further the motivation to seek the anticipated reward and seek out more drugs

Also, the environment in which drug use/procurement takes place will also increase dopamine release and further desire for the drug

Question 8

Basic Circuit of Reward System

Answer 8

PFC eactovates NA; NA is responsible for suppressing the sensations of reward
-this means NA receives constant activation from amygdala and hippocampus

Activation of NA inhibits the presence of pleasure through GABA release to PFC

Question 9

Reward Circuit

Answer 9

1. VTA activated by PFC (EAA), DTA (ACh), and hypothalamus (orexin)
2. Dopamine Neurons from VTA project to NA
3. DA is released to NA, which inhibits NA
4. NA activity decreases, causing sensation of pleasure in PFC

Question 10

Reward Feedback Circuit

Answer 10

NA projects back to VTA and releases GABA and well as Dynorphin
-dynorphin binds kappa-opioid receptors

This stops further release of DA

Question 11

VTA Activation via Opiods

Answer 11

Increase in endogenous opioid signals activates mu-receptors, which inhibit local interneurons in VTA that Suppress DA release to NA

Also activates interneurons in NA (inhibits GABA neurons) and activates PFC

Results in euphoria

Question 12

What causes the poor inhibitory control seen in addictive behaviors?

Answer 12

Chronic drug exposure alters morphology of neurons in dopamine-regulated circuits
-this results in abnormal NT levels in brain

If in orbitofrontal cortex, compulsive behavior results

If in cingulate gyrus, this regulates disinhibition

Question 13

Role of Memory and Drug Dependency

Answer 13

Lasting memory created that associates good feelings with circumstances and environments, creating “conditioned associations”
-this causes person to seek out more drugs

Question 14

Physical Dependency

Answer 14

Due to excessive noradrenergic output from locus ceruleus and CREB-dependent upregulation of target genes in locus ceruleus

-Upregulates DFosB and AP-1
—upregulates expression of EAA receptors
—promotes drug seeking

Question 15

CREB Protein

Answer 15

Targets dynorphin, so it does not allow it to decrease DA release from VTA

Question 16

Dopamine modulation in Amygdala

Answer 16

Retrieval of fear memories

Question 17

Dopamine modulation in VTA

Answer 17

Signals prediction error between expected outcome and actual reward

Question 18

Dopamine modulation in NA

Answer 18

Assignment of salience to certain stimuli and mediate decisions that seek a desirable situation

• acute stress increase DA short term
• chronic stress results in CRF inducing DA release that was pleasureable to aversive, this switches emotional response

Question 19

Dopamine Modulation in Hippocampus

Answer 19

Place and direction contextual info about environment in which stimuli is experienced

Question 20

Domaine Modulation in Substantia nigra and dorsal striatum

Answer 20

Motor response toward a desirable cue w goal of engaging in activity that elicits reward