Neurophysiology of Reward and Addiction

Question 1

What is saliency?

Answer 1

Something important in the surrounding environment worth paying attention to

Question 2

What is hedonia?

Answer 2

Stimuli or environmental changes that are arousing or elicit an attentional-behavioral switch

Question 3

In what areas do drugs of abuse increase extracellular dopamine concentrations?

Answer 3

Limbic regions, including the NA

Question 4

How do drugs such as cocaine, amphetamine, methamphetamine, and ecstasy increase dopamine?

Answer 4

By directly inhibiting dopamine reuptake or promoting dopamine release

Question 5

How do drugs such as nicotine, alcohol, opiates, and marijuana increase dopamine?

Answer 5

Indirectly via other neuron receptors that modulate dopamine levels

Question 6

What makes up the mesolimbic system?

Answer 6

Nucleus accumbens, ventral tegmental area, limbic system, and prefrontal cortex

Question 7

What is the main function of the NA?

Answer 7

Suppress sensations of pleasure/reward

Question 8

How does the NA work?

Answer 8

It is constitutively activated by a constant trickle of EAAs from the hippocampus, amygdala, or PFC. It releases GABA at the PFC to keep the brain in a reward-neutral state

Question 9

How does the reward circuit work?

Answer 9

VTA neurons project to NA and release dopamine which inhibits NA neurons. Inhibition of NA (inhibitory GABAergic) neurons results in sensation of pleasure

Question 10

How is the VTA activated during reward?

Answer 10

By EAAs (PFC), orexin (hypothalamus), or ACh (tegmental nuclei)

Question 11

What is the reward feedback circuit?

Answer 11

Projections of GABAergic neurons from the NA back to the VTA. Dynorphin (an opioid) released as a cotransmitter that binds to kappa-opioid receptors in VTA. Together suppress additional release of DA from VTA to halt reward process

Question 12

What is the dopamine-independent reward pathway?

Answer 12

Utilizes endogenous opioids

Question 13

How do opioids work in the reward network?

Answer 13

Activate dopaminergic neurons via mu receptors in VTA
Activate local interneurons in NA which inhibit GABAergic neurons
Activate PFC directly

Question 14

What region of the brain is involved in compulsive behavior?

Answer 14

Orbitofrontal cortex

Question 15

Which region of the brain regulates disinhibition

Answer 15

Cingulate gyrus

Question 16

What are conditioned associations?

Answer 16

Memories that associate good feelings with the circumstance and environment in which they occur

Question 17

What is CREB?

Answer 17

cAMP response-element binding protein, is shorter acting (days)

Question 18

What is physical dependency due to?

Answer 18

Excessive noradrenergic output from locus ceruleus and CREB-dependent upregulation of target genes in locus ceruleus

Question 19

What is long-term potentiation?

Answer 19

Persistent increase in synaptic strength following high-frequency stimulation of chemical synapse. Increased phosphorylation of AMPA receptors and insertion of AMPA receptors in post-synaptic membrane (short term). Also activation of calcium-calmodulin-CREB (long term).

Question 20

What is a prominent target for CREB?

Answer 20

Dynorphin- Which is working with GABA in the feedback circuit to halt Dopamine release

Question 21

When would you see an increase in FosB (or AP-1)?

Answer 21

with increased stress or abusing drugs