Lecture 5: Dopamine - reward & addiction

What is dopamine?

neuromodulator

aids in movement, attention, learning and addiction

How is dopamine synthesised?

Tyrosine (food - almonds, avocado, cheese) → L-DOPA → Dopamine

(1) tyrosine hydroxylase

(2) amino acids/DOPA decarboxylase

an additional step → noradrenaline (beta-hydroxylase)

What are the two reigons of the brain that synthesise dopamine?

Substantia Nigra (SN) for motor control

Ventral Tegmental Area (VTA) for motivation, emotional response, rewards, desire & addiction

these have axons projecting to the pre-frontal cortex, striatum, nucleus accumbends, amygdala and hippocampus

What causes Parkinson’s

• death of dopamine cells in substantia nigra

What are symptoms of Parkinson’s disease + why

lack of SN dopamine thus decreased motor control

motor tremors; inert + rigid motion → cognitive impairment, demenita, often reduced executive function

What is a morphological feature associated with parkinsons

typically due to DA breakdown area is stained black

whereas in parkinson people - pale

What is the cure for parkinsons’

• there is no cure only treatment to reduce symptoms

• L-DOPA (can cross BBB unlike DA)+ other to increase DA synthesis

• deep brain stimulation

• side effects → hypersexuality, gambling, addiction, impulsivity (relates to reward effects of DA VTA system)

What are the roles of dopamine in reward + motivation briefly

(1) codes for reward relative to expectation

(2) codes effort costs - balances cognitive effort with reward

Describe dopamine’s role in reward prediction error

• if a reward is unexpectedly recived → DA release peaks

• when a stimulus is repeatedly preceded by a reward → DA release peaks in response to stimulus rather than reward

• if a reward is expected by not recieved → following stimulus DA still released but when reward not given, DA neurons supressed

Thus, things are only rewarding if the reward is MORE than expected

• (if a reward is expected, DA not released)

Also, DA codes if the predicted outcome was corrected

What are some common rewards

• real - food + sex - biological/tangiable

• symbolic - money = value (so gain = reward)

• virtual - game points

Describe how dopamine helps motor control

• similar to reward, tells brain if e.g. did the limb move correctly

• provides the feedback

Describe what the Value-modulated attentional capture task informs regarding dopamine

• Performing experiment where task asks whether the line in the diamond is horizontal or vertical

• Circles are distractors but encode reward related cues

• People with higher propensity to addiction will readily learn the reward cue (immediate gratification) opposed to pursue the adaptive functioning goal

  • Chose the distractor at the expense of the goal

• rats choose opiod over food

Describe DA’s role in effort costs + and what skews this?

effort cost = cognitive effort = aversive feeling + opportunity cost

• DA balances how worthwile it is to engage

• cognitive effort/task persistence only justifiable when progress outpaces cost

• thus tasks with low sucess, reward → disengaging

• lack of episodic future thinking - unable to hold long-term goals in working memory - thus unable to recongise future value

• leads to choosing immediate gratification

What is episodic future thinking + how does it relate to dopamine + can we fix?

• Poor EFT ability is linked to an inability to appreciate the benefits of a task + delaying gratification

  • Lower working memory means cannot hold long-term outcomes + poorer DA balance of opprotunity cost

• Can train EFT by imagery training - practice holding a visual image

Describe why gambling is so addictive

• dopamine → released only when reward more than expected

• gambling rewards ALWAYS unpredictable

• while avergae loss is consistent - cannot guess when will win/lose (not in a repeating pattern)

What is drug addiction?

• chronic relapsing disorder consiting of compulsive pattern of drug seeking and taking behaviour

• cues → craving → behaviour

• distressing not to obey craving

• occurs at the expense of other goals + persists despite aversive consequence

• initially substance is rewarding however later anticipation gives high instead

what are DA drugs + brieft describe mode of action

• cocaine - blocks reuptake

• amphetamine - reverses reuptake (push out) + thus prevents reuptake

Describe the action of cocaine

blocks reuptake → increases DA concentration in cleft → artifically makes everything more rewarding (DA consistently present)

What are the two forms of amphetamines

• ice/meth - most pure

• speed - less pure

What is the structure of amphetamines? + consequence

mirror image of cocaine - ampethamine has longer effect once taken than cocaine

Describe the action of amphetamines

• Stimulant

• Mirror image of cocaine - longer effect after taken

• Reverses reuptake transporters - actively expells DA and NA out of neuron + thus prevents DA uptake

  • Things not usually rewarding are again more rewarding

  • Leads to long term brain changes due to addiction + overstimulation causing cell death

Describe the risk of stimulants

overstimulate the brain → neuron damage

Describe the dopaminergic mechanisms of addictive drugs

make everything artificially more rewarding than expected

normally when reward expected, no DA release during reward (only during stimuli). Due to artificial action of drug → DA always higher → always rewarding

the more DA released due to drugs - the greater the high

Compare intravenous, oral and nasal intake of drugs

• the faster the effects the more addictive - as more immediately associate reward with drug

intravenous > nasal > oral

Describe the problem with addiction recovery

1. drugs initiate wanting causing craving

2. dysregulation of top-down control

i.e. bottom-up approach overtakes top-down

this means behaviour is guided by stress + stimuli opposed to pre-frontal cortex / cognitive control

thus, struggle to resist craving → allows craving to control behaviour

Compare bottom-up and top-down approaches to behaviour

top-down = brain controls behaviour

bottom-up = stress/stimuli drives behaviour

Why does top-down approach fail in addiction?

• excess DA release damages pre-frontal cortex

• adolescence → underdeveloped pre-frontal cortex

• stress

Are all addictive drugs dopaminergic?

• no, some drugs can be enjoyable without DA or be addictive with less DA

• proposed that while DA controls behaviour modulation, something else may control the high/pleasure e.g. opiod system

note: Addiction can exist beyond drugs too → e.g. real, symbolic etc,