Reward Circuitry: Nucleus Accumbens and Addiction

Question 1

How do D1R-expressing MSNs in the NAc project back to the VTA and what is their effect?

Answer 1

Directly

Inhibit VTA

Question 2

How do D2R-expressing MSNs in the NAc project back to the VTA and what is their effect?

Answer 2

Indirectly - via ventral pallidum

Disinhibit VTA

Question 3

Which marker is only expressed by D1R-MSNs?

Answer 3

Dynorphin

Question 4

Which marker is only expressed by D2R-MSNs?

Answer 4

Enkephalin

Question 5

What are the 2 possible mechanisms for the way a reward preferentially activates D1-MSNs (over D2-MSNs)?

Answer 5

DA activates D1-MSNs and inhibits D2-MSNs - LTP and LTD

Excitatory input distinguishes between D1- and D2-MSNs

Question 6

Where does the NAc receive input from?

Answer 6

VTA (DAergic)
PFC (glutamatergic)
Ventral hippocampus
Basolateral amygdala
Medial thalamus

Question 7

How does optogenetic PFC stimulation affect MSN activation?

Answer 7

Equally activates D1- and D2-MSNs

Question 8

How does optogenetic vHPC stimulation affect MSN activation?

Answer 8

Preferentially activates D1-MSNs

Question 9

What is the effect of cocaine on NT modulation?

Answer 9

Blocks DA reuptake

Question 10

What is the effect of methamphetamine on NT modulation?

Answer 10

Enters presynaptic terminal
Causes intracellular DA release from vesicles - via VMAT
Released into synaptic cleft - via monoamine transporters

Question 11

What is the non-contingent method of studying the effects of cocaine in rodents?

Answer 11

Experimenter-administered
Place rodent in enclosure
Measure increased locomotion, conditioned place preference (for box paired with cocaine administration than neutral box)
Easiest

Question 12

What is the contingent method of studying the effects of cocaine in rodents?

Answer 12

Self-administered
Give IV cocaine when presses lever/nose poke
Increase fixed ratio over time
More representative of real substance abuse - must work to obtain drug
Technically difficult

Question 13

What is a fixed ratio?

Answer 13

Number of lever presses required to receive drug

Question 14

What are the synaptic effects of non-contingent cocaine in the NAc?

Answer 14

Shortly after administration - increased number of silent synapses, increased number of dendritic spines
Long-term - silent synapses filled with AMPARs - increased number of functional synapses - maintenance of increased number of spines

Question 15

What are the synaptic effects of prolonged cocaine withdrawal in contingent vs. non-contingent methods?

Answer 15

Contingent - no change in rectification - no change in Ca-permeable AMPARs
Non-contingent - increased rectification - increased GluA2-lacking AMPARs
In both - increased AMPAR/NMDAR ratio, increased silent synapses, increased spine density