T3L1 reward and addiction

Question 1

addiction/dependence def

Answer 1

a persistent order of brain function in which compulsive drug use occurs despite serious negative consequences for the afflicted individual

both physical and psychological

Question 2

withdrawal symptoms def

Answer 2

negative physiological and emotion features that occur when the drug is not taken

generally the opposite effect of the positive that the drug makes

Question 3

tolerance

Answer 3

diminished response to the effects of a given amount of drug following repeated exposures to the drug

larger dose for same effect

Question 4

where do drugs act on the brain

Answer 4

the reward system:

the mesocorticolimbic pathway is formed of:

1. mesolimbic system
2. mesocortical system

also involves

• amygdala
• prefrontal cortex
• hippocampus

Question 5

anticipation of reward involves the __

Answer 5

nucelus accumbens (NAcc)

Question 6

neurotransmitter of reward

Answer 6

dopamine - DA

• has an error signal
• the reinforcement system is activated by unexpected stimuli, and by presence of reward relative to prediction

anticipation releases more dopamine than actual reward
unexpected reward also releases a lot

unpredictable - nucleus accumbens (needs to be learned)
predictable - temporal lobe (has been learned)

Question 7

function of reinforcement system

Answer 7

detect reinforcing stimulus:

• recognise something good has happened
• learning

strengthen neural connections:

• between neurons that detect stimulus and neurons that produce response
• LTP

Question 8

drug induced synaptic plasticity

Answer 8

• in NAcc (early reinforcement)
• dorsal striatum (caudate, putamen- instrumental conditioning)

consolidate:

• drug wanting
• drug seeking
• drug taking

Question 9

mesocorticolimbic dopamine system - natural

Answer 9

• pathway for reward and reinforcement
  s15

natural reinforcers eg sex, food cause extracellular DA release into NAcc (into synapse)

• the behaviours activating system is reinforced, so more likely to be repeated
• addictive drugs cause more powerful and reliable activation than natural stimuli

Question 10

effects of drugs on DA system

pshycostimulants

opiates

alcohol

nicotine

Answer 10

psychostimulants - direct action on dopaminergic neurons in NAcc

opiates- indirectly inhibit GABAergic interneurons in VTA (disinhibition of VTA DA neurons)

alcohol - disinhibition of VTA DA neurons

nicotine- increases NACC DA, stimulates nicotinic cholinergic receptors on mesocorticolimbic DA neurons

maybe check out s20 that pretty cool huh B)

Question 11

cocaine and amphetamines -

Answer 11

DA AGONISTS
- potentiate monoaminergic transmission by inhibition of DA, 5HT, NA reuptake inhibitors

(coke inhibits reuptake transporter, amphetamine reverses it)

coke:

• psychotic behaviour
• long term decrease in DA transporters and receptors
• hypofrontality

Question 12

all drugs of abuse cause

Answer 12

increase in AMPA/NMDA ratio

- increase in basal excitatory synaptic strength

Question 13

associative learning

Answer 13

cells that fire together wire together

coincidence firing between sensory pathways and mesocorticolimbic pathway induce LTP
- thus sensory information, people, places, emotions etc. present at the time when drug induced DA release occurs will become associated with taking the drug

DOPAMINE ENHANCES LTP:

• modifies glutamatergic transmission in LTP
• synaptic remodelling- more spines and dendritic branches
• long term changes even after months of absetenance

ie higher risk of doing coke at a club if you’ve done it there before, even years later

Question 14

opiates

Answer 14

action:

• on endogenous opioid receptors
• inhibitory
• many receptors (m, k, d)
• morphine works on mu receptors

reward:

• disinhibition of DA neurons in VTA
• action at opiate receptors in NAcc independent of DA release

see s35 for mechanism

physical dependence to opiates:
- chronic activation of opiate receptors leads to homeostatic mechanism that compensates for changes leading to physical dependence

acute morphine: inhibits LC firing
chronic treatment: LC neurons return to normal firing rate
withdrawal: dramatic increase in LC firing s38,39

Question 15

alcohol

Answer 15

1. GABAa agonist (inhibitory)
2. NMDA antagonist (blocks excitation)

large doses inhibit functioning of most voltage gated channels

increase DA release in NAcc

opiate system also involved: naltrexons (an opiate antagonist) stops craving in alcohols

physical dependence:
chronic alcohol leads to downregulation of GABAa receptors, upregulation of NMDA
- in presence of alcohol, firing balance returns to normal
- in withdrawal, balance shifts to excitation
s40

Question 16

nicotine

Answer 16

acts as nicotinic acetylcholine receptors (nAChRs) (ligand gated ion channels)

• release DA into NAcc

due to:

• activation of receptors on cell body to increase firing in VTA
• facilitation of DA release by presynaptic receptors in NAcc

opiate involvement system
- both opiate and DA antagonists can block nicotine induced behaviours and self administration