Dopamine

Question 1

What are the primary neurotransmitters?

Answer 1

Glutamate and GABA - the mainworkhorses of the brain. Directly mediate the transition of information between neurons either via activation or inactivation

Question 2

What are neuromodulators?

Answer 2

These affect the response properties of a neuron - don’t carry primary information themselves e.g. dopamine, serotonin, noradrenaline, acetylcholine
if u have these, neuron may fire more, less, or at different frequencies

Question 3

Can neurotransmitters be neuromodulators and vice versa?

Answer 3

Some neurotransmitters act as neuromodulators - GABA at GABAa receporos

some neuromodulators act as neurotransmitters ach at nicotinic ACh receptors

Question 4

What are the diffuse modulatory systems?

Answer 4

Specific populations of neons which project diffusely and modulate the activity of glutamate and gaba in their target areas: dopamine, serotonin, noradrenaline and acetylcholine

Question 5

5 steps of regulation of neurotransmitter

Answer 5

1. Neurotransmitter is synthesized
2. Neurotranmitter is packaged into vesicles
3. Neurotransmitter is released when vesicles fuse
4. Neurotransmitter binds to and activates post synaptic receptors
5. Neurotransmitter diffuses away and is transported back

Question 6

What is dopamine involved n?

Answer 6

Motivation and reward
Addiction
Movement

Question 7

Where are dopamine neurones?

Answer 7

Cell bodies in the midbrain

Project into the forebrain

Question 8

What are the 3 dopamine systems?

Answer 8

Nigrostriatal system
Mesolimbic system
Mesocortical system

Question 9

Where projections occur in the nigrostriatal system?

Answer 9

Substantia nigra projections to neostriatum

Question 10

What is the nigrostriatal system involved in?

Answer 10

Role in movement

Question 11

What does dysfunction of the nigrostriatum system lead too?

Answer 11

Parkinsons disease - destruction of DA projections from SN to basal ganglia

Huntingdons - destruction of DA target neurons in striatum

Question 12

Where projections occur in the mesolimbic system?

Answer 12

Ventral tegmental area projection to the nucleus accumbens

Question 13

What is the mesolimbic system involved in?

Answer 13

Reward

Question 14

What does dysfunction of the msolimbic system result in?

Answer 14

Addiction - most drugs of abuse lead to enhanced DA release in the NaCC

Question 15

What projections occur in the mesocortical system?

Answer 15

VTA projections to the prefrontal cortex

Question 16

What is the mesocortiyal system involved in?

Answer 16

Working memory and planning

Question 17

What does dysfunction in the mesocortical system lead too?

Answer 17

Schizophrenia / depression

Question 18

How is dopamine synthesised?

Answer 18

Tryosine (amino acid which comes from diet) is catalysed (made) by tyrosine hydroxyls (TH) - rate limiting, slowest step
L DOPA is then made, which is catalysed by dopa decarboxylase
Leading to dopamine

Question 19

What happens when dopamine is synthesised?

Answer 19

It is stored in the vesicles

Question 20

How is dopamine controlled?

Answer 20

By regulating tyrosine hydroxlyase activity - controls amount of dopamine available for release

Question 21

What are the 3 ways that dopamine is controlled?

Answer 21

1. Feedback inhibition by end products - dopamine competes for binding with a cofactor, which pushes it out, too much dopamine lowers TH activity - Down regulation of synthesis
2. Presynaptic activity (DA release) leads to phosphorylation of TH (via autoreceptor) which increases its activity - Up regulation
3. Prolonged activity in the presynaptic neuron leads to an increase in transcription of the TH gene leading to more enzyme synthesized - Up regulation

Question 22

What does transcription mean?

Answer 22

Changing RNA to protein

Question 23

What drugs affect dopamine synthesis and storage?

Answer 23

Reserpine - impairs the storage of monoamines (what dopamine comes from) in synaptic vesicles - so they are empty, resulting in no dopamine release

L - DOPA - the precursor of dopamine, bypasses rate limiting TH step, converts it into dopamine so increasing the pool

AMPT - inactivates TH - only used experimentally, not in treatment

Question 24

What can L dopa treat?

Answer 24

Parkinsons disease - most effective drug, but as the disease progresses, give more L dopa - at some point, it will stop working
side effects: can develop gambling issues

Question 25

How did scientists find out about reserpine and L DOPA?

Answer 25

When they gave reserpine (comes from plant) to rabbits, they had trouble moving
Give them L dopa - recovers the process

Question 26

How was the role of some neurotransmitter systems revealed by drugs?

Answer 26

Reserpine was first of all used to treat high blood pressure - but caused depression - started to realise dopamine was also involved in motivation, not just movement

Question 27

How is dopamine released?

Answer 27

Depolarisation of presynaptic membrane, influx of calcium through voltage gated channels. Ca2+ dependent vescicle docking and release

Question 28

How is dopamine reuptaken / metabolised?

Answer 28

Single terminated by reuptake into the axon terminal by transporters powered by electrochemical gradient (dopamine transporters)

in the cytoplasm, it is:
reloaded back into vesicles
enzymatically degraded by monomine axidates or COMT

Question 29

What drugs affect dopamine release and reuptake?

Answer 29

Cocaine, amphetamine and methylphenidate - all block the rupture of monoamines into the terminals - so more dopamine in synaptic clef, extended action of dopamine on post-synaptic neuron

amphetamine reverses transporter, so instead of sucking it, more is released, lasts hours, whereas cocaine is short lived

Selegiline and entacopone - inhibits MAOS and COMT - prevents the breakdown, increases the pool. they have antidepressant activity and can be used to treat Parkinson’s

Question 30

What do mutations in COMT cause?

Answer 30

Linked to psychiatric disorders e.g. schizophrenia and addiction