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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
Q

What is included in the D1 like receptor family?

A
  • D1

- D5

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26
Q

What’s included in the D2 like receptor family?

A
  • D2
  • D3
  • D4
27
Q

What is the structure of dopamine receptors?

A
  • Have 7 transmembrane domains
  • They’re GPCR’s
  • N terminus found extracellularly
  • C terminus found intracellularly
28
Q

How are D1 like receptors coupled and what’s the cascade involved in order to increase excitability?

A

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
Q

How are D2 receptors coupled and what do they do?

A

Gi coupled receptors

-Inhibit adenylyl cyclase

30
Q

What can D1 and D2 receptors do?

A

Can come together to form heterodimers

31
Q

How are the D1 and D2 heterodimer coupled and what does it lead to?

A

Gq coupled

-Lead to activation of phospholipase C

32
Q

What is serotonin released from and where is it projected from?

A

Released from serotonergic neurons which project from the raphe nuclei

33
Q

What happens when serotonin levels increase in the cortex?

A

Heightened preception

34
Q

What happens when serotonin levels increase in the hypothalamus?

A

Reduced appetite

35
Q

What happens when serotonin levels increase in the amygdala?

A

Elevated mood

36
Q

How is serotonin synthesised?

A
  • 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
Q

What happens with serotonin at the synapse?

A
  • Serotonin in vesicles are released and bind to postsynaptic receptors
  • There are also 5HT1D autoreceptors inhibit release of serotonin
38
Q

What happens if serotonin levels are too low?

A

Depression

39
Q

What happens if serotonin levels are too high?

A

Psychosis

40
Q

How is serotonin regulated at the synapse?

A

-Excess serotonin transported into neuron by serotonin transporter and is metabolised by MAO

41
Q

How can we treat depression?

A
  • Block serotonin transporter

- Block MAO

42
Q

How many types of serotonin receptors are there and what are they?

A

7 types

  • 6 GPCR
  • Only 5HT3 is not GPCR as its an ion channel receptor
43
Q

LOOK AT SLIDE FOR ALL SEROTONIN RECEPTORS AND THERE FUNCTIONS

A

LOOK AT SLIDE FOR ALL SEROTONIN RECEPTORS AND THERE FUNCTIONS

44
Q

What do autoreceptors do?

A

Inhibit cell firing and transmitter release at the terminal regions

45
Q

When are autoreceptors not autoreceptors?

A

If found postsynaptically, they aren’t autoreceptors

46
Q

What do transporters usually do?

A

Usually take the neurotransmitter back up into the presynaptic terminal

47
Q

Structure of transporters

A
  • Have 12 transmembrane domains

- C terminus and N terminus found intracellularly

48
Q

What neurons release acetylcholine?

A

Cholinergic neurons release acetylcholine

49
Q

What cholinergic pathways are there and where do they project to?

A
  • 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
Q

What neurons are found in the striatum and what do they release?

A

There are cholinergic interneurons which are found in the striatum and they release Ach

51
Q

What is Ach important in?

A

Important in learning and memory

52
Q

How is Ach synthesised?

A

Acetyl CoA and choline come together to form acetylcholine

53
Q

What happens to Ach at the synapse?

A

-Ach in vesicles and released into the cleft
-Ach act on postsynaptic receptors(nAchR, mAchR)
-

54
Q

How is Ach regulated?

A

Regulated by acetylcholinesterase which break down acetylcholine into acetate and choline which are recycled

55
Q

What happens in alzheimer’s?

A

Cholinergic receptors become degenerative

56
Q

How do you treat alzheimer’s?

A

To treat you increase acetylcholine by inhibiting acetylcholinesterase

57
Q

What does amphetamine cause the release of?

A

Release cytosolic amines

58
Q

What does prolonged use of amphetamine cause?

A

Prolonged use causes degeneration of amine containing nerve terminals

59
Q

What does amphetamine do?

A

Increases alertness and locomotor stimulations

60
Q

What are the therapeutic uses of amphetamine?

A

Are ADHD and appetite suppressants

61
Q

What does cocaine block?

A

Blocks catecholamine reuptake

62
Q

What does cocaine increase the levels of?

A

Increases dopamine

63
Q

What can cocaine cause?

A

Can cause euphoria

64
Q

What does nasal inhalation of cocaine lead to?

A

Leads to necrosis of nasal mucosa

NEEUUUUUURRRRRRROOOOO (20 decks)

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