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NEEUUUUUURRRRRRROOOOO > Neurotransmitter systems III:Monoamines > Flashcards

Neurotransmitter systems III:Monoamines Flashcards

1
Q

How many systems of the monoamine modulating systems of the brain and what is there common principle?

A

4 systems with common principles:

  • Small set of neurons at core
  • Arise from the brain stem
  • One neuron influence many others
  • Synapses release transmitter molecules into extracellular fluid
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2
Q

Metabotropic receptors and their effect on AC or PLC

A 
5HT1-Inhibits AC
5HT2-Stimulates PLC
Dopamine 1-Stimulates AC
Dopamine 2-Inhibits AC
Noradrenaline beta-Stimulates AC
Noradrenaline alpha1-Stimulates PLC
Noradrenaline alpha2-Inhibits AC

AC=adenylyl cyclase
PLC=Phospholipase C

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3
Q

What does noradrenaline consist of?

A

Consist of noradrenergic neurons which project from the locus coeruleus to different parts of the brain

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4
Q

What nervous system is noradrenaline important in?

A

Important in CNS

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5
Q

What is noradrenaline involved in?

A

Involved in hyperarousal in flight or fight situation

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6
Q

What can Noradrenaline activate on the presynaptic membrane?

A

NA can also activate presynaptic alpha 2 adrenergic receptors(autoreceptor) which inhibits release of noradrenaline

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7
Q

How is NA modulated?

A

Modulated by reuptake of excess NA into neuron and broken down by monoamine oxidase A

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8
Q

What does reserpine do to NA?

A

Depletes NA stores by inhibiting vesicular uptake

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9
Q

What does amphetamine do to NA?

A

Amphetamine enters vesicles displacing NA into cytoplasm, increasing NA leakage out of neuron

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10
Q

What does cocaine do to NA?

A

Cocaine blocks NA re-uptake

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11
Q

What is dopamine released from?

A

Released from dopadrenergic neurons

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12
Q

How many pathways are involved in the movement of dopamine and what are they?

A

4 pathways involved in movement:

  • Mesocortical pathway
  • Tuberohypophyseal pathway
  • Nigrostriatal pathway
  • Mesolimbic pathway
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13
Q

What does the nigrostriatal pathway involve?

A

Involve neurons that project from the substantia nigra to striatum of the brain where dopamine gets released

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14
Q

What does the mesolimbic pathway involve?

A

Involve neurons that project from the VTA to different regions of the brain such as amygdala, hippocampus as well as the nucleus accumbens

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15
Q

What does the mesolimbic pathway have a role in?

A

Has an important role in reward

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16
Q

What is psychotic like behavior due to?

A

Psychotic like behaviour is due to large hyperactivity of the mesolimbic pathway

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17
Q

What does the mesocortical pathway involve?

A

Involve neurons that project from the VTA to the cortex

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18
Q

What happens in the tuberohypophyseal pathway?

A

DA is released from neurons to activate adjacent neurons but also can act as a neurohormone

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19
Q

What does hyperactivity of dopamine receptors in CT2 help with?

A

Hyperactivation of dopamine receptors in regions of the brain involved in vomiting such as the CT2 helps with emesis

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20
Q

How is dopamine synthesised?

A
  • Precursor molecule of DA is tyrosine
  • Tyrosine converted to DOPA via tyrosine hydroxylase
  • DOPA gets metabolised to dopamine via DOPA decarboxylase
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21
Q

What happens to DA at the synapse?

A
  • DA is in vesicles and get released
  • DA acts in D1 and D2 receptors post-synaptically
  • D2 also found presynaptically and inhibit DA
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22
Q

How is the action of DA terminated?

A

Termination of DA:

-DA taken up again into neuron and is broken down by monoamine oxidase B

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23
Q

What are the ways we can increase the levels of DA?

A
  • Could block the reuptake of DA and it will accumulate
  • Block the monoamine oxidase B
  • Can use L-DOPA which is a precursor of DA
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24
Q

How do we treat the symptoms of schizophrenia?

A
  • Block the DA receptors

- Antipsychotics block D2 receptors

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25
What is included in the D1 like receptor family?
- D1 | - D5
26
What's included in the D2 like receptor family?
- D2 - D3 - D4
27
What is the structure of dopamine receptors?
- Have 7 transmembrane domains - They're GPCR's - N terminus found extracellularly - C terminus found intracellularly
28
How are D1 like receptors coupled and what's the cascade involved in order to increase excitability?
Are Gs coupled - Activate adenylyl cyclase - Increase cAMP - PKA will add a phosphorous group to DARPP-32 - This will induce other second messenger systems to increase excitability
29
How are D2 receptors coupled and what do they do?
Gi coupled receptors | -Inhibit adenylyl cyclase
30
What can D1 and D2 receptors do?
Can come together to form heterodimers
31
How are the D1 and D2 heterodimer coupled and what does it lead to?
Gq coupled | -Lead to activation of phospholipase C
32
What is serotonin released from and where is it projected from?
Released from serotonergic neurons which project from the raphe nuclei
33
What happens when serotonin levels increase in the cortex?
Heightened preception
34
What happens when serotonin levels increase in the hypothalamus?
Reduced appetite
35
What happens when serotonin levels increase in the amygdala?
Elevated mood
36
How is serotonin synthesised?
- Precursor molecule for serotonin is tryptophan - Tryptophan comes from our diet - Tryptophan hydroxylase converts it to 5-hydroxytryptophan - Then converted to serotonin via DOPA decarboxylase
37
What happens with serotonin at the synapse?
- Serotonin in vesicles are released and bind to postsynaptic receptors - There are also 5HT1D autoreceptors inhibit release of serotonin
38
What happens if serotonin levels are too low?
Depression
39
What happens if serotonin levels are too high?
Psychosis
40
How is serotonin regulated at the synapse?
-Excess serotonin transported into neuron by serotonin transporter and is metabolised by MAO
41
How can we treat depression?
- Block serotonin transporter | - Block MAO
42
How many types of serotonin receptors are there and what are they?
7 types - 6 GPCR - Only 5HT3 is not GPCR as its an ion channel receptor
43
LOOK AT SLIDE FOR ALL SEROTONIN RECEPTORS AND THERE FUNCTIONS
LOOK AT SLIDE FOR ALL SEROTONIN RECEPTORS AND THERE FUNCTIONS
44
What do autoreceptors do?
Inhibit cell firing and transmitter release at the terminal regions
45
When are autoreceptors not autoreceptors?
If found postsynaptically, they aren't autoreceptors
46
What do transporters usually do?
Usually take the neurotransmitter back up into the presynaptic terminal
47
Structure of transporters
- Have 12 transmembrane domains | - C terminus and N terminus found intracellularly
48
What neurons release acetylcholine?
Cholinergic neurons release acetylcholine
49
What cholinergic pathways are there and where do they project to?
- one projects from the nucleus basalis to the cortex where Ach is released - The other projects from the septum to the hippocampus and important in memory
50
What neurons are found in the striatum and what do they release?
There are cholinergic interneurons which are found in the striatum and they release Ach
51
What is Ach important in?
Important in learning and memory
52
How is Ach synthesised?
Acetyl CoA and choline come together to form acetylcholine
53
What happens to Ach at the synapse?
-Ach in vesicles and released into the cleft -Ach act on postsynaptic receptors(nAchR, mAchR) -
54
How is Ach regulated?
Regulated by acetylcholinesterase which break down acetylcholine into acetate and choline which are recycled
55
What happens in alzheimer's?
Cholinergic receptors become degenerative
56
How do you treat alzheimer's?
To treat you increase acetylcholine by inhibiting acetylcholinesterase
57
What does amphetamine cause the release of?
Release cytosolic amines
58
What does prolonged use of amphetamine cause?
Prolonged use causes degeneration of amine containing nerve terminals
59
What does amphetamine do?
Increases alertness and locomotor stimulations
60
What are the therapeutic uses of amphetamine?
Are ADHD and appetite suppressants
61
What does cocaine block?
Blocks catecholamine reuptake
62
What does cocaine increase the levels of?
Increases dopamine
63
What can cocaine cause?
Can cause euphoria
64
What does nasal inhalation of cocaine lead to?
Leads to necrosis of nasal mucosa

NEEUUUUUURRRRRRROOOOO (20 decks)

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