Neurotransmitter Systems III : Monoamines Flashcards

1
Q

What are the CNS systems that control behaviour?

A

→ Autonomic nervous system
→ Hypothalamic-pituitary neurohormones
→ Diffuse monoamine systems

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2
Q

What are examples of monoamines?

A

→ Noradrenaline
→ Serotonin
→ Dopamine
→ ACh

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3
Q

What neurons project from the central core?

A

→ Adrenergic
→ Serotonergic
→ Dopaminergic
→ Cholinergic

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4
Q

What are the four systems with common principles?

A

→ Small set of neurons at the core
→ Arise from the brain stem
→ One neuron influences many others
→ Synapses release transmitter molecules into extracellular fluid

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5
Q

What is the main source of noradrenergic neurons in the brain?

A

→ Locus Coeruleus

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6
Q

What is the main source of serotonergic neurons in the brain?

A

→ Raphe Nuclei

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7
Q

What are the main sources for the dopaminergic neurons in the brain?

A

→ Substantia nigra

→ Ventral tegmental area

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8
Q

What are the main sources for cholinergic neurons in the brain?

A

→ Basal forebrain and brain stem complexes

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9
Q

What 3 things are involved in fast point-to-point signalling? (type of channel and transmitter)

A

→ Neurotransmitters producing excitatory or inhibitory potentials
→ Ligand gated ion channels
→ Glutamate, GABA, ACh

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10
Q

What 3 things are involved in slow transmission?

A

→ Neurotransmitters and neuromodulators
→ G-Protein coupled receptors
→ Monoamines, peptides, ACh

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11
Q

Where do noradrenergic neurons project from?

A

→ Central core

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12
Q

What 5 areas of the brain do noradrenergic neurons project to?

A
→ Cortex
→ Amygdala
→ Hypothalamus
→ Spinal cord
→ Cerebellum
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13
Q

What is the locus coerulus involved in?

A

→ Making the brain more responsive

→ Information processing

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14
Q

What is noradrenaline involved with?

A

→ Gambling

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15
Q

What are withdrawal symptoms driven by?

A

→ Hyperexcitability from noradrenaline

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16
Q

What receptors does noradrenaline act on?

A

→ G coupled post-synaptic receptors

→ activates presynaptic alpha 2 receptors

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17
Q

What are noradrenergic alpha 2 receptors also called and why?

A

→autoreceptors

→ When noradrenaline binds it inhibits the release of noradrenaline

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18
Q

What do low levels of noradrenaline lead to?

A

→ Depression like behaviour

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19
Q

How is the action of noradrenaline terminated?

A

→ Inside the membrane there are NET transporters
→ Uptake excess noradrenaline inside the neuron
→ Once inside they get broken down by monoamine oxidase

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20
Q

How do amphetamines work?

A

→ They enter vesicles and displace the NA into the cytoplasm which causes NA leakage out of the neuron

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21
Q

What does cocaine do?

A

→ Blocks NA reuptake

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22
Q

What is the main action of noradrenaline?

A

→ Inhibitory ( alpha 2)

→ Also excitatory (alpha/beta)

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23
Q

How is noradrenaline terminated?

A

→ Neuronal uptake

→ MAO

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24
Q

What is the main cell body of noradrenaline?

A

→ Locus coerulus

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25
Q

When are noradrenergic neurons active?

A

→ When awake

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26
Q

Where are high densities of noradrenergic neurons found?

A

→ Brainstem
→ Hypothalamus
→ Medial temporal lobe

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27
Q

What are the functions of noradrenergic neurons?

A

→ Arousal
→wakefulness
→ mood
→ Blood pressure regulation

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28
Q

Describe the nigrostriatal pathway?

A

→ Dopaminergic neurons project from the substantia nigra to the striatum

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29
Q

Why does Parkinsons occur?

A

→ Dopaminergic neurons become degenerated

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30
Q

Describe the mesolimbic pathway?

A

→ Dopaminergic neurons project from the ventral TA to
→ amygdala
→ Hippocampus
→ Nucleus Accumbens

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31
Q

What is the function of the nucleus Accumbens?

A

→ Rewards and pleasure

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32
Q

What is schizophrenic behaviour due to?

A

→ Hyperactivity of the mesolimbic pathway

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33
Q

Describe the mesocortical pathway?

A

→ Dopaminergic neurons projecting from the VTA to the cortex

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34
Q

Describe the tuberohypophyseal pathway?

A

→ Dopamine is released from the hypothalamus directly to the circulation

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35
Q

In what situation does dopamine act as a neurohormone?

A

→ It goes to the anterior pituitary and inhibits the release of prolactin

36
Q

What receptors are activated during emesis?

A

→ D2 receptors

37
Q

Describe the formation of dopamine?

A

→Tyrosine gets metabolised by tyrosine hydroxylase
→ this forms DOPA
→ DOPA gets metabolised by DOPA decarboxylase to form dopamine

38
Q

What receptors does dopamine act on?

A

→ D1 and D2

39
Q

What kind of receptors are D2 receptors and where are they found?

A

→ Pre and post synaptically

→ Autoreceptors

40
Q

What is the function of D2 receptors?

A

→ WHen dopamine binds to the autoreceptors they inhibit the release of dopamine

41
Q

What breaks down dopamine?

A

→ Monoamine oxidase

42
Q

What do low and high levels of dopamine lead to?

A

→ High - Schizophrenia

→ Low - Depression

43
Q

What is a way to treat parkinsons?

A

→ Blocking the reuptake of dopamine

→ Stopping monoamine oxidase

44
Q

What is a way to treat schizophrenia?

A

→ Blocking dopamine receptors

45
Q

What is the D1 receptor coupled with?

A

→ Gs couples receptors

46
Q

What is the D2 receptor coupled with?

A

→ Gi coupled receptor

47
Q

Where are D1 and D2 receptors found?

A

→Striatum
→ Limbic system
→ Thalamus
→ Hypothalamus

48
Q

Where are D3 receptors found?

A

→ Limbic system

49
Q

Where are D4 receptors found?

A

→ cortex and limbic system

50
Q

What are the functions of dopamine?

A

→ Movement
→ Addiction
→ Hormone release
→ Vomiting

51
Q

Where do serotonergic neurons project from?

A

→ Raphe Nuclei

52
Q

Where do serotonergic neurons project to?

A
→ Cortex
→ Cerebellum
→ Striatum
→ Hypothalamus
→ Hippocampus
→ Amygdala
53
Q

What does serotonin increase in the cortex lead to?

A

→ Heightened perception

54
Q

What does serotonin increase in the hypothalamus lead to?

A

→ Reduced appetite

55
Q

What does serotonin increase in the amygdala lead to?

A

→ Elevated mood and emesis

56
Q

What drugs increase serotonin?

A

→ Antidepressants

→ Ecstasy

57
Q

Describe the formation of Serotonin?

A

→ Tryptophan gets metabolised by tryptophan hydroxylase
→ this forms 5 hydroxytryptophan
→ 5 hydroxytryptophan gets metabolised into serotonin

58
Q

What does too much serotonin lead to?

A

→ Psychotic like effects

59
Q

What does too little serotonin lead to?

A

→ Depression effects

60
Q

What do antidepressants block?

A

→ SERT reuptake

61
Q

What does activation of 5-HT 1D receptor lead to?

A

→ Inhibition of serotonin

→ Autoreceptor

62
Q

What metabolizes serotonin?

A

→ MAO

63
Q

How many serotonin receptor subtypes are there?

A

→ 14

64
Q

What is the 5-HT1 receptor for?

A

→ mood
→ Migraine
→ autoreceptor

65
Q

What are the excitatory serotonin receptors?

A

→ 5HT2

→ 5HT3

66
Q

What is the function of serotonin?

A
→ Mood
→ Psychosis 
→ Sleep/wake
→ Feeding behaviour
→ Pain
→ Migraine
67
Q

What are the 3 cholinergic neuron pathways?

A

→ Nucleus basalis to the cortex
→ Septum to the hippocampus
→ Substantia nigra to the thalamus

68
Q

Where are cholinergic interneurons found?

A

→ in the striatum

69
Q

Why do people suffer from memory impairment?

A

→ Degeneration of cholinergic neurons

70
Q

What are the two kinds of Ach receptors?

A

→ Nicotinic

→ Muscarinic

71
Q

How is ACh formed?

A

→ Acetyl CoA and choline join

72
Q

Where are ACh receptors found in the brain?

A

→ Basal forebrain
→ Hippocampus
→ Striatum

73
Q

What is the function of Ach?

A

→ Arousal
→ Epilepsy
→ Learning and memory
→ Motor control

74
Q

What are the functions of histamine?

A

→ sleep
→ Wake
→ vomiting

75
Q

What are the functions of purines?

A
→ Sleep
→ pain
→ Neuroprotection
→ Addiction
→ Seizures 
→ anti convulsant
76
Q

What are the functions of neuropeptides?

A

→ Pain

77
Q

What is melatonin involved in?

A

→ sleep regulation

→M1 and M2

78
Q

What are the effects of amphetamine?

A

→ Alertness
→ Euphoria
→ Anorexia
→ Confidence / lack of tiredness

79
Q

What does prolonged use of amphetamines cause?

A

→ Neurotoxicity
→ Degeneration of amine containing nerve terminals
→ Cell death

80
Q

What does cocaine increase?

A

→ Dopamine
→ Noradrenaline
→ Serotonin

81
Q

What happens to transporters when you take cocaine?

A

→ blockades of dopamine transporters

→ accumulates in the cleft

82
Q

What are the metabotropic receptors for the monoamines?

A
→ noradrenaline 
- beta - stimulates adenylyl cyclase
-alpha 1 - stimulates PLC
-alpha 2 - inhibits adenylyl cyclase
→ dopamine 
D1- stimulates adenylyl cyclase
D2 inhibits adenylyl cyclase
→ Serotonin
5-HT1 - inhibits adenylyl cyclase
5-HT2 stimulates pLC
83
Q

What is the effect of reserpine?

A

→ Depletes NA stores by inhibiting vesicular uptake

84
Q

What are the 5-HT receptor functions? (1-7)

A
→ 5HT1 - inhibitory - limbic system - mood
→ 5HT2 - excitatory - limbic
→ 5HT3 - excitatory- medulla - vomiting
→ 5HT4 - presynaptic faciliation
→ 5HT 6 -7 - sleep
85
Q

What are the neurotransmitter transporter?

A
→ dopamine - DAT
→ 5-HT - SERT
→ NA - NET
→ glutamate - EAAT1 
→ dopamine - VMAT2 (vesciles)
86
Q

What are the functions of ACh receptors (M1-M3)

A

→ M1 - excitatory
→ M2 presynaptic inhibition
→ M3 - excitatory glandular/smooth muscle effects