Neurophysiology of Drug Addiction

Question 1

drug addiction is the result of?

Answer 1

act of normal neurophysiological events/systems by the drugs of addiction:

• pleasure/reward systems
• learning and memory

Question 2

Producing pleasure- core system

Answer 2

VTA (Ventral tegmental area)-> inc dopamine–> NA

Question 3

VTA receives input from?

Answer 3

• prefrontal cortex- EAA
• lateral hypothalamus- Orexin
• Laterodorsal tegmental nucleus- ACH

Question 4

Nucleus Accumbens

Answer 4

• third nucleus in the striatum

- referred to as ventral striatum

Question 5

NA- receives input from?

Answer 5

• VTA (dopamine)

- excitatory inputs (EAA)- prefrontal cortex, amygdala, hippocampus

Question 6

NA- output to?

Answer 6

prefrontal cortex (GABA)
-also back to VTA (GABA)

Question 7

opioid inputs to?

Answer 7

-VTA- inhibit GABA interneurons- inc dopamine release in NA

Question 8

Producing pleasure- system

Answer 8

• VTA- inc dopamine
• NA- dec GABA
• prefrontal cortex- pleasure!!!

Question 9

Producing pleasure- activation

Answer 9

• prefrontal cortex, laterodorsal tegmental nucleus- inc EAA
• lateral hypothalamic nucleus- inc orexin
• EAA and orexin–> VTA- inc dopamine
• NA- dec GABA
• prefrontal cortex

Question 10

Preventing pleasure

Answer 10

Activation of NA:

• prefrontal cortex, amygdala, hippocampus- inc EAA
• NA- inc GABA
• prefrontal cortex- absence of pleasure

Question 11

opioids- major action?

Answer 11

• inhibit GABA interneuron in VTA
• VTA releases more dopamine in NA
• pleasure

Question 12

to produce pleasure:

Answer 12

• act VTA
• inhibit NA
• less GABA in prefrontal cortex
• experience pleasure

Question 13

to inhibit pleasure:

Answer 13

• act NA
• more GABA in prefrontal cortex
• prevent pleasure

Question 14

Drugs of abuse- act what systems

Answer 14

• pleasure/reward systems

- learning and memory- permanent neurophysiological changes

Question 15

drugs that act GPCRs

Answer 15

• Opiates- Gi

- cannabis- CB-1R- dopamien release

Question 16

Drugs that alter ion channels

Answer 16

• nicotine- influx of sodium

- ethanol/PCP- antagonist at NMDA Rs

Question 17

DRugs that interfere w re-uptake mechanisms

Answer 17

• Cocaine- inhibit reuptake of dopamine

- Amphetamines- reversal of dopamine reuptake transporters

Question 18

PCP and ethanol- do what

Answer 18

disrupt EAA inputs to NA- so less GABA released

Question 19

agents that inc activity of VTA dopaminergic neurons

Answer 19

• cocaine
• amphetamines
• cannabis

Question 20

nicotine- act what?

Answer 20

-act nACHR on VTA neurons- release dopamine

Question 21

Drugs do what?

Answer 21

• VTA- inc dopamine release to NA

- euphoria!!

Question 22

drug addiction

Answer 22

• LTP in VTA dopaminergic neurons

- if NMDA R in VTA blocked- blocks effects of these drugs

Question 23

long-term changes in neurons as a result of addictive drugs

Answer 23

CREB induction (cAMP response element binding protein)

• neuropeptides
• enzymes for making NTs
• R’s

Question 24

what does CREB do to produce effects of drugs?

Answer 24

in NA:

• inc prod of dynorphin!! (opioid substance, binds to Kappa-Rs)
• NA sends a GABA-ergic and dynorphin-ergic input back to VTA
• dynorphin released from NA- turns input from the VTA off: desensitization!!

Question 25

Act of CREB in locus ceruleus and periaqueductal gray assoc w?

Answer 25

-physical dependence

Question 26

changes in CREB are?

Answer 26

• temporary!

- return to normal within a wk of drug abstinee

Question 27

long term response to drug addiction

Answer 27

delta-FosB (regulator of transcription)

-in NA, leads to prod of proteins that remodel dendrites (inc synapses)