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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 receptors?

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
When are noradrenergic neurons active?
→ When awake
26
Where are high densities of noradrenergic neurons found?
→ Brainstem → Hypothalamus → Medial temporal lobe
27
What are the functions of noradrenergic neurons?
→ Arousal →wakefulness → mood → Blood pressure regulation
28
Describe the nigrostriatal pathway?
→ Dopaminergic neurons project from the substantia nigra to the striatum
29
Why does Parkinsons occur?
→ Dopaminergic neurons become degenerated
30
Describe the mesolimbic pathway?
→ Dopaminergic neurons project from the ventral TA to → amygdala → Hippocampus → Nucleus Accumbens
31
What is the function of the nucleus Accumbens?
→ Rewards and pleasure
32
What is schizophrenic behaviour due to?
→ Hyperactivity of the mesolimbic pathway
33
Describe the mesocortical pathway?
→ Dopaminergic neurons projecting from the VTA to the cortex
34
Describe the tuberohypophyseal pathway?
→ Dopamine is released from the hypothalamus directly to the circulation
35
In what situation does dopamine act as a neurohormone?
→ It goes to the anterior pituitary and inhibits the release of prolactin
36
What receptors are activated during emesis?
→ D2 receptors
37
Describe the formation of dopamine
→Tyrosine gets metabolised by tyrosine hydroxylase → this forms DOPA → DOPA gets metabolised by DOPA decarboxylase to form dopamine
38
What receptors does dopamine act on?
→ D1 and D2
39
What kind of receptors are D2 receptors and where are they found?
→ Pre and post synaptically | → Autoreceptors
40
What is the function of D2 receptors?
WHen dopamine binds to the autoreceptors they inhibit the release of dopamine
41
What breaks down dopamine?
→ Monoamine oxidase
42
What do low and high levels of dopamine lead to?
→ High - Schizophrenia | → Low - Depression
43
What is a way to treat parkinsons?
→ Blocking the reuptake of dopamine | → Stopping monoamine oxidase
44
What is a way to treat schizophrenia?
→ Blocking dopamine receptors
45
What is the D1 receptor coupled with?
→ Gs couples receptors | →Adenylyl cyclase
46
What is the D2 receptor coupled with?
→ Gi coupled receptor | →Opens up K+ channels and blocks Ca channels.
47
Where are D1 and D2 receptors found?
→Striatum → Limbic system → Thalamus → Hypothalamus
48
Where are D3 receptors found?
→ Limbic system
49
Where are D4 receptors found?
→ cortex and limbic system
50
What are the functions of dopamine?
→ Movement → Addiction → Hormone release → Vomiting
51
Where do serotonergic neurons project from?
→ Raphe Nuclei
52
Where do serotonergic neurons project to?
→ Cortex → Cerebellum → Striatum → Hypothalamus → Hippocampus → Amygdala
53
What does serotonin increase in the cortex lead to?
→ Heightened perception
54
What does serotonin increase in the hypothalamus lead to?
→ Reduced appetite
55
What does serotonin increase in the amygdala lead to?
→ Elevated mood and emesis
56
What drugs increase serotonin?
→ Antidepressants | → Ecstasy
57
Describe the formation of Serotonin?
→ Tryptophan gets metabolised by tryptophan hydroxylase → this forms 5 hydroxytryptophan → 5 hydroxytryptophan gets metabolised into serotonin
58
What does too much serotonin lead to?
→ Psychotic like effects
59
What does too little serotonin lead to?
→ Depression effects
60
What do antidepressants block?
→ SERT reuptake
61
What does activation of 5-HT 1D receptor lead to?
→ Inhibition of serotonin | → Autoreceptor
62
What metabolizes serotonin?
→ MAO
63
How many serotonin receptor subtypes are there?
→ 14
64
What is the 5-HT1 receptor for?
→ mood → Migraine → autoreceptor
65
What are the excitatory serotonin receptors?
→ 5HT2 | → 5HT3
66
What is the function of serotonin?
→ Mood → Psychosis → Sleep/wake → Feeding behaviour → Pain → Migraine
67
Which 5HT receptor is ionotropic?
5HT3
68
What are the 3 cholinergic neuron pathways?
→ Nucleus basalis to the cortex → Septum to the hippocampus → Substantia nigra to the thalamus
69
Where are cholinergic interneurons found?
→ in the striatum
70
Why do people suffer from memory impairment?
→ Degeneration of cholinergic neurons
71
What are the two kinds of Ach receptors?
→ Nicotinic | → Muscarinic
72
How is ACh formed?
→ Acetyl CoA and choline join
73
Where are ACh receptors found in the brain?
→ Basal forebrain → Hippocampus → Striatum
74
What is the function of Ach?
→ Arousal → Epilepsy → Learning and memory → Motor control
75
What are the functions of histamine?
→ sleep → Wake → vomiting
76
What are the functions of purines?
→ Sleep → pain → Neuroprotection → Addiction → Seizures → anti convulsant
77
What are the functions of neuropeptides?
→ Pain
78
What is melatonin involved in?
→ sleep regulation | →M1 and M2
79
What are the effects of amphetamine?
→ Alertness → Euphoria → Anorexia → Confidence / lack of tiredness
80
What does prolonged use of amphetamines cause?
→ Neurotoxicity → Degeneration of amine containing nerve terminals → Cell death
81
What does cocaine increase?
→ Dopamine → Noradrenaline → Serotonin
82
What happens to transporters when you take cocaine?
→ blockades of dopamine transporters | → accumulates in the cleft
83
What are the metabotropic receptors for the monoamines?
→ 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
84
What is the effect of reserpine?
→ Depletes NA stores by inhibiting vesicular uptake
85
What are the 5-HT receptor functions? (1-7)
→ 5HT1 - inhibitory - limbic system - mood → 5HT2 - excitatory - limbic → 5HT3 - excitatory- medulla - vomiting → 5HT4 - presynaptic faciliation → 5HT 6 -7 - sleep
86
What are the neurotransmitter transporter?
→ dopamine - DAT → 5-HT - SERT → NA - NET → glutamate - EAAT1 → dopamine - VMAT2 (vesciles)
87
What are the functions of ACh receptors (M1-M3)
→ M1 - excitatory → M2 presynaptic inhibition → M3 - excitatory glandular/smooth muscle effects
88
What is a therapeutic use of amphetamine?
ADHD
89
Name the members of the opioid peptide family
→Proopioimelanocortin →Proenkephalin →Prodynorphin →Pronociceptin
90
What are the opioid receptors?
→MOP (B-endorphin) →DOP (Enkephalins) →KOP (Dynorphins) →NOP (Nociceptin/OFQ)
91
How does cocaine work?
→Blocks catecholamine reuptake | increases DA, stimulant effect
92
What are the pharmacokinetics of cocaine?
→HCl salt, inhaled and i.v. administration →Nasal inhalation less intense, leads to necrosis of nasal mucosa
93
What does loss of 5HT lead to?
exaggerated response to sensory stimuli
94
Where are histamine cell bodies?
hypothalamus

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