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PHYS - NEURO > 5. MONOAMINES > Flashcards

5. MONOAMINES Flashcards

1
Q

What are 4 monoamine systems & their neuronal cell bodies?

A
  1. Noradrenergic - locus coerculus
  2. Dopaminergic - VTA (ventral tegmental area) & Substantia Nigra
  3. Serotonin - Raphe nuclei
  4. Acetlylcholine - Basal forebrain, brain stem complexes
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2
Q

What is the diffuse modulatory system?

A
  • The monoamine systems have a diffuse-modulatory effect
  • This means that the effect is modulatory rather than direct inhibition or excitation like GABA & Glycine
  • They have a slower, widespread effect compared to point to point communication . Neurotransmitters are released & then diffuse out to their receptors
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3
Q

What is the noradrenergic system?

A
  • The noradrenergic system uses the neurotransmitter Noradrenaline or norepinephrine
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4
Q

What are the functions of noradrenaline?

A
  1. Mood
  2. Arousal
  3. Wakefulness
  4. Exploration
  5. Blood pressure regulation
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5
Q

What’s the neuronal cell body for the noradrenergic system & it’s projections?

A
  • The neuronal cell body is located in the LOCUS COERCULUS

- It projects to cortical regions, hypothalamus, amygdala, spinal cord, cerebellum etc.

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6
Q

Describe the synthesis & storage of noradrenaline

A
  • Noradrenaline is synthesised from dopamine
  • Tyrosine -> L-DOPA -> Dopamine -> Noradrenaline
  • DOPAMINE BETA HYDROXYLASE is the enzyme involved in converting Dopamine to Noradrenaline
  • NA is stored in vesicles by the transporter VMAT
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7
Q

Describe the re-uptake & degradation of Noradrenaline

A
  • Re-uptake by of NA NERT/NET (Noradrenaline re-uptake transporters) into pre-synaptic neurone
  • Can be metabolised by MONOAMINE OXIDASE which terminates NA activity
  • Can also be degraded by Catechol-O-methyltransferase
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8
Q

Where can noradrenaline receptors be found & what are the three types?

A
  • Noradrenaline receptors are G-protein coupled receptors
  • They can be located post-synaptically & pre-synaptically
    1. Alpha 1
    2. Alpha 2
    3. Beta
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9
Q

What are the effects of the alpha 1 NA receptor?

A
  • Alpha 1 receptors = PLC
  • Converts PIP2 -> DAG + IP3
  • Increase in intracellular Ca2+ = smooth muscle contraction
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10
Q

What are the effects of the alpha 2 NA receptor?

A
  • Alpha 2 can act as an autoreceptor, meaning it can have an inhibitory effect
  • Alpha 2 is negatively coupled to Adenylate cyclase = decreased cAMP & Ca2+. Inhibits NA release
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11
Q

What are the effects of the beta NA receptor?

A
  • The beta receptor is positively linked to adenylate cyclase = increased cAMP & Ca2+
  • Causes smooth muscle relaxation & contraction of cardiac muscle
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12
Q

What do reserpine & amphetamine do?

A
  • Both reserpine & amphetamine are drugs affecting the noradrenergic system
  • Reserpine - blocks NA re-uptake, depletes NA stores causing an accumulation of NA
  • Amphetamine - enters vesicles & displaces NA, leading to NA accumulation
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13
Q

What is the dopaminergic system & it’s neuronal body ?

A
  • The dopaminergic system uses the neurotransmitter dopamine which is a monoamine & catecholamine
  • The cell body of dopaminergic neurones is located in the VTA (Ventral Tegmental area) & the Substantia Nigra which project to various areas of the brain forming 4 pathways
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14
Q

What are the four pathways of the dopaminergic system?

A
  1. NIGRO-STRIATAL
  2. MESOLIMBIC
  3. MESOCORTICAL
  4. TUBERO-HYPOPHYSEAL PATHWAY
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15
Q

What is the nigrostriatal pathway of the dopaminergic system?

A
  • Projects from substantia nigra to the striatum of the basal ganglia
  • Involved in motor control
  • Disorders e.g Parkinsons - degradation of nigro striatal neurones
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16
Q

What is the mesolimbic pathway of the dopaminergic system?

A
  • Mesolimbic pathway projects from the ventral tegmental area to the nucleus accumbens of the basal ganglia
  • Involved in pleasure & reward
  • Hyperactivity of mesolimbic pathway is associated with positive symptoms of schizophrenia
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17
Q

What is the mesocortical pathway of the dopaminergic system?

A
  • Mesocortical pathway projects from the ventral tegmental area to the prefrontal cortex
  • Involved in motivation, emotion & other cognitive functions
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18
Q

What is the tubero-hypophyseal pathway of the dopaminergic system?

A
  • Dopamine is released from the hypothalamus & transported to pituitary via circulation
  • Acts to inhibit prolactin release
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19
Q

What are the functions of dopamine?

A
  1. Movement
  2. Reward
  3. Vomiting
  4. Addiction
  5. Inhibition of prolactin release
20
Q

Give some examples of disorders of the dopaminergic system?

A
  • Parkinson’s, ADHD, Schizophrenia, Emesis
21
Q

Describe dopamine synthesis & storage

A
  • Dopamine is synthesised from Tyrosine
  • Tyrosine -> L-DOPA -> Dopamine
  • Tyrosine -> L-DOPA by Tyrosine hydroxylase
  • L-DOPA -> Dopamine by Dopa decarboxylase
  • Store in vesicles by VMAT (Vesicular Monoamine transporter)
22
Q

What are the two classes of dopamine receptor?

A
  1. D1-like receptor - stimulate AC

2. D2-like receptor - inhibit AC

23
Q

What are the sub-types of the Dopamine receptors?

A
  • D1-like receptors have two sub-types: D1 & D5

- D2-like receptors have three sub-types: D2, D4, D3

24
Q

What is the mechanism of action for D1-like receptors?

A
  • D1 like receptors are Gs protein receptors that stimulate adenylate cyclase
  • Adenylase cyclase increases cAMP formation.
  • cAMP activates PKA (Protein Kinase A) which phosphorylates a dopamine signalling molecule called DARPP-32
25
Q

What is the mechanism of action for D2-like receptors?

A
  • D2 like receptors can be located post & pre-synaptically
  • D2 like receptors are coupled to Gi/o so they inhibit adenylate cyclase to decrease DA by causing K+ efflux leading to hyperpolarisation
  • D2 & D3 receptors can act as autoreceptors
26
Q

Describe the re-uptake & degradation of dopamine

A
  • Dopamine re-uptake occurs by DAT
  • Dopamine can be metabolised by an isoenzyme of monoamine oxidase known as MONOAMINE OXIDASE B
  • Dopamine can also be degraded by CATECHOL-O-METHYLTRANSFERASE
27
Q

Give three ways in which dopamine levels can be increased e.g to treat a disorder

A
  1. Administer a pre-cursor of dopamine such as L-DOPA which can be metabolised into dopamine
  2. Block the dopamine re-uptake transporters (DAT) to cause dopamine accumulation
  3. Inhibit monoamine oxidase B to prevent the degradation of dopamine
28
Q

What are the neuronal cell bodies of the serotonergic system & it’s projections?

A
  • The serotonergic system uses serotonin as it’s neurotransmitter
  • Serotonergic neurones project from the raphe nuclei to areas such as the cortex, striatum, thalamus, hypothalamus, spinal cord etc.
29
Q

**Describe the synthesis & storage of serotonin?

A
  • Serotonin is synthesised from L-tryptophan
  • L-tryptophan -> 5-hydroxL-tryptophan -> Serotonin
  • L-tryptophan -> 5-hydroxyL-tryptophan by TRYPTOPHAN HYDROXYLASE
  • 5-hydroxyl-L-tryptophan -> Serotonin by DOPA DECARBOXYLASE or L-AROMATIC ACID DECARBOXYLASE
  • Serotonin is transported into vesicles by VMAT
30
Q

Describe the re-uptake & degradation of serotonin

A
  • Serotonin is taken up from the synaptic cleft by SERT (Serotonin re-uptake transporters)
  • Serotonin is degraded by Monoamine oxidase
31
Q

What are the functions of serotonin?

A
  1. Mood
  2. Sleep/Wake
  3. Appetite
32
Q

Give two ways to increase serotonin

A
  1. Block the SERT - to prevent re-uptake of serotonin

2. Inhibit Monoamine Oxidase to prevent serotonin breakdown

33
Q

Describe the properties of serotonin receptors

A
  • Serotonin receptors are typically located post-synaptically
  • There are 14 subtypes of the Serotonin receptor, they are all G-protein coupled receptors except for 5HT3 which is LIGR
34
Q

What are the effects of 5HT1-7 receptors?

A
  1. 5HT1 - excitatory, limbic system -> mood, migraine
  2. 5HT2 - excitatory, limbic system & cortex
  3. 5HT3- excitatory, medulla, vomiting - found in teh chemoreceptor trigger zone, blocking it causes anti-emetic effect
  4. 5HT4 - pre-synaptic facilitation
  5. 5HT6&7 - Cognition, sleep
35
Q

What are the autoreceptors for serotonin, dopamine & NA?

A 
Serotonin = 5HT1D
Dopamine = D2 & D3
NA = alpha 2
36
Q

What are the re-uptake transporters for serotonin, dopamine & NA?

A 
Serotonin = SERT
Dopamine = DAT
NA = NERT/NET
37
Q

What are the neuronal cell bodies of the cholinergic neurones & it’s projections?

A
  • The cholinergic system uses acetylcholine as it’s neurotransmitter
  • The neuronal cell bodies are located in the basal forebrain & the brain stem complexes (striatal interneurones), which project out to cortex, hippocampus & hypothalamaus
38
Q

What are the functions of acetylcholine?

A
  1. Memory, learning
  2. Motor control -striatum
  3. Reward
  4. Arousal
  5. Modulation of pain
39
Q

How is acetyl choline synthesised & stored?

A
  • Acetyl choline is synthesized by combing Acetyl CoA & Choline using the enzyme CHOLINE ACETYL TRANSFERASE
  • Acetyl choline is transported into vesicles by VAchT
40
Q

Describe the degradation & re-uptake of acetylcholine

A
  • Acetyl CoA is degraded into acetate & choline by choline esterases
  • The choline is then taken up by choline carriers
41
Q

What are some disorders of the cholinergic system?

A
  • Schizophrenia, epilepsy, ADH, depression, anxiety, addiction
42
Q

Give two ways that disorders of the cholinergic system can be treated?

A
  1. ANTICHOLINESTERASES - inhibit the breakdown of acetylcholine known as Neostigmine
  2. Prevent the re-uptake of choline e.g Hemicholinium
43
Q

What are the two classes of Ach receptors?

A
  1. LIGR/NICOTINIC ACETYLCHOLINE RECEPTOR

2. G-PROTEIN/ MUSCARINIC ACETYCHOLINE RECEPTOR

44
Q

What are the 5-subclasses of muscarinic receptors & what do they do?

A

M1 - excitatory
M2 - pre-synaptic inhibition
M3 - excitatory smooth muscle effects
M4 & M5

45
Q

What are the effects/consequences of amphetamine?

A
  • Increases NA or DA:
  • Increase alertness or aggression
  • Euphoria/excitement
  • Increased confidence or lack of tiredness
  • Anorexia
  • E.g MDMA (ecstasy), methylphenidate
  • Acts as an appetite suppressant & used to treat narcolepsy

PHYS - NEURO (18 decks)

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