Lecture 6 - Dopamine

Question 1

What is the mechanism of action of cocaine?

Answer 1

Increases the spatial (distance) and temporal (time) distribution of dopamine
By antagonising the 
norepinephrine transporter (NET),
serotonin reuptake transporter (SERT)
and dopamine transporter (DAT)

Does not increase dopamine release
Does not bind to the receptors themselves

Question 2

How do neurotransmitter reuptake transporters work?

Answer 2

Co transport the neurotransmitter with sodium, making using of the sodium electrochemical gradient

Question 3

What is the mechanism of action of amphetamines?

Answer 3

Competitive antagonist of the
norepinephrine transporter (NET),
dopamine transporter (DAT)
and vesicular monoamine pump (VMAT-2)

Question 4

Why does amphetamine have different effects from cocaine in terms of mood and addiction?

Answer 4

Doesn’t act on SERT so has less effect on mood than cocaine

Possibly reverses NET and DAT, causing dopamine release, making it more addictive than cocaine?

Question 5

How can cocaine be administered?

Answer 5

Nasally/injected as hydrochloride salt
Mixed with sodium bicarbonate and smoked as crack cocaine
Freebased - mixed with ammonia or other base, then evaporated

Question 6

How is dopamine synthesised?

Answer 6

Tyrosine converted into DOPA by tyrosine hydroxylase
Dopa converted into dopamine by dopa decarboxylase

Dopamine can go on to become noradrenaline and then adrenaline

Question 7

What are the dopamine receptors?

Answer 7

All GPCRs
D1 like: D1 and D5, coupled to Gs
D2 like: D2, D3 and D4, coupled to Gi

Question 8

Why do people respond differently to the same drug on different occasions?

Answer 8

Drug response mediated by effect on receptors

Receptor profile can change over time

Question 9

What are the 5 main dopamine pathways in the brain and what is each involved in?

Answer 9

1. Nigrostriatal - motor function
2. Mesolimbic - learning, motivation and desire
3. Mesocortical - reward anticipation and consumption
4. Tuberoinfundibular - prolactin release
5. No name - possibly pain

Question 10

What regions of the brain does the mesolimbic pathway pass between?

Answer 10

From the ventral tegmental area (midbrain) to the nucleus accumbens (in the striatum)

Question 11

Describe how electrophysiological recordings of dopamine release were used to demonstrate the function of dopamine in the mesolimbic pathway

Answer 11

Monkeys given a reward (e.g. juice), dopamine neurons fire 100ms after
Monkeys learn to associate a predictor (e.g. bell) with the juice
Dopamine neurons fire after the bell, but not when they get the juice
If the bell sounds but they get no juice, dopamine firing decreases

Question 12

What are the short term and long term functions of dopamine?

Answer 12

Short term: sustains behaviour that leads to the reward (motivation)
Long term: Allows you to predict reward based on a cue (reward prediction)

Question 13

What is a theory for why some people are more susceptible to drug addiction?

Answer 13

Variability in D2 receptor density
Those with low levels experience less reward based conditioning
Upon taking drugs they experience huge reward based conditioning
Long term, D2 receptors may become down regulated, diminished capacity for new associations