Week 5- Dopamine

Question 1

what is dopamine?

Answer 1

-Catecholamine neurotransmitter

Question 2

what is dopamine synthesised from and via what pathway?

Answer 2

Synthesised from tyrosine via tyrosine hydroxylase and DOPA decarboxylase

Question 3

what is dopamine metabolised by?

Answer 3

Metabolism by MAO-B in the

synaptic terminal

Question 4

what happens to dopamine once it is in the synaptic terminal?

Answer 4

• the action potential comes in to the terminal
• this causes the release of the neurotransmitter
• the neurotransmitter then acts on post synaptic receptor
• the action is then terminated by removing it from the synaptic cleft either back into the pre-synaptic terminal through the dopamine transporter or into non-neuronal cells via EMT

Question 5

what drives the dopamine transporter?

Answer 5

a dopamine-Na+
symporter
-sodium moves down its gradient and dopamine moves up against its gradient

Question 6

When dopamine is taken up by non-neuronal cells what metabolises it?

Answer 6

Metabolised by MOA-A and –B and COMT

Question 7

how many sub types of dopamine receptors is there? also what are they then further divided down to?

Answer 7

5

divided into D1-like and D2-like

Question 8

what members are in D1-like receptors?

Answer 8

D1 and D5

Question 9

what members are in D2-like receptors?

Answer 9

D2,3,4

Question 10

what type of receptor are dopamine receptor?

Answer 10

GPCRs

Question 11

what is the different downstream signalling for D1-like? what type of effect and found where?

Answer 11

-D1-like act via Gαs to increase cAMP.
PKA phosphorylates DARPP-32 which inhibits protein phosphatase-1
-these are excitatory and found at post-synapitc

Question 12

what is the different downstream signalling for D2-like? what type of effect and found where?

Answer 12

-D2-like act via Gαi/o to decrease cAMP.
The βγ subunits open K+
channels and inhibit voltage-gated Ca2+ channels
-Inhibitory
• Post-synaptic-decreaced excitability due to increase K leaving causing hyperpolarisation
-pre-synaptic- inhibit calcium channels which decreases amount in cell leading to presynaptic inhibition leading to less neurotransmitter being released

Question 13

how does dopamine have a potential dual effect?

Answer 13

it can be excitatory or inhibitory depending on which type of receptor it binds to

Question 14

what are the agonists at the dopamine receptors?

Answer 14

• Dopamine
• Bromocriptine (non-selective)
• Apomorphine (non-selective)
• Cabergoline (D2>D1)
• Pergolide (D2>D1)
• Pramipexole (D2-like selective)
• Ropinirole (D2-like selective)
• Aripiprazole (PA; D2-like)

Question 15

what are the antagonists at the dopamine receptors?

Answer 15

Haloperidol (non-selective)
Sulpiride (D2-like)
Domperidone (D2-like)
Metoclopramide (D2-like)

Question 16

what are the different 4 pathways that dopamine works on?

Answer 16

• Nigrostriatal pathway
• Mesolimbic pathway
• Mesocortical pathway
• Tuberohypophyseal (tuberoinfundibular)

Question 17

what does the nigrostriatal pathway include?

Answer 17

– 75% of DA in the brain
– Cell bodies in substantia nigra (midbrain),
projecting to the striatum

Question 18

what does the Mesolimbic pathway pathway include?

Answer 18

– VTA to limbic areas, notably the nucleus
accumbens, hippocampus and amygdala
– Behavioural - reward pathways
– Schizophrenia (+ve symptoms)
– Drugs of abuse (cocaine, amphetamine)

Question 19

what does the Mesocortical pathway pathway pathway include?

Answer 19

– VTA to frontal cortex
– Cognition and thought
– Schizophrenia (-ve symptoms)

Question 20

what does the Tuberohypophyseal (tuberoinfundibular) pathway pathway pathway include?c

Answer 20

– Hypothalamus to pituitary
– Control of secretion
• DA inhibits prolactin secretion

Question 21

what is the D1-like receptors expression like?

Answer 21

• D1 receptors are the most abundant. Expressed at high density in nigrostriatal,
mesolimbic and mesocortical pathways
– D5 more restricted distribution (limbic)

Question 22

what is the D2-like receptors like?

Answer 22

• D2 receptors highest density in nigrostriatal, mesolimbic and tuberohypophyseal
pathways; also in the CTZ (medulla)
– D3 more restricted and weaker expression
– D4 weaker expression