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PN3312 > Serotonin > Flashcards

Serotonin Flashcards

1
Q

Name a variety of processes which involve serotonin

A
  1. Anxiety
  2. Learning
  3. Vasoldilaton
  4. Hunger
  5. Pain
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2
Q

How does serotonin accomplish its varied functions?

A
  1. Processes everywhere in the brain despite only manufactured in a few areas
  2. Variety of receptors, 7 families with specific localisations and functions
  3. Transmitted in a variety of ways (one-to-one or bulk transmission)
  4. State dependent effects
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3
Q

How is serotonin synthesised?

A
  • Is made from an essential amino acid L-Tryptophan
  • Undergoes hydrosylation by tryaptophan hydroxylase
    (type 1 is non neuronal, type 2 is neuronal)
  • Then decarboxylated to serotonin by L-aromatic acid decarboxylase
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4
Q

How is serotonin degraded?

A
  • By monoamine oxidase through the substitution of NH2 with OH
  • Acted on by aldehyde dehydrogenase to form -COO gorup
  • Otherwise addition of glucose where it is processed by the kidneys and excreted
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5
Q

Why does an increased protein diet not necessarily result in higher brain serotonin levels?

A
  • Dietary tryptophan faces competition with other neural amino acids to cross blood brain barrier
  • Therefore high protein diet increases competition
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6
Q

How is serotonin released at the synapse?

A
  • Taken into vesicles by transporter VMAT2 where it is then released into the post synaptic cleft
  • 5-HT transporters reuptake serotonin from the cleft
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7
Q

How do serotonin depletion drugs work?

A

Para-chlorophenylamine blocks tryptophan hydroxylase

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8
Q

How do serotonin agonists work?

A
  • SSRIs block serotonin transporters and therefore increase levels in the cleft
  • MDMA (para-chloranphetamine) induces synaptic release however this results in a long term depletion of serotonin release
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9
Q

What are the 4 different positions of serotinergic synapses?

A
  • Axo-dendritic (classic)
  • Axo-somatic - closer to where the action potential is generated so generating a more significant response
  • Axo-axonic - affect only one axon terminal
  • Dendro-dendritic - mad shit
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10
Q

What are the properties of 5-HT1A receptors?

A
  • G-coupled
  • Inhibits adenyl cyclase, reduced cAMP which inhibits cAMPk
  • Enhancement of K+ channels and therefore an inhibitory effect
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11
Q

What are 5-HT1A receptors implicated in?

A

Anxiety and depression, high levels in hippocampus, amygdala and dorsal raphe nucleus

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12
Q

What polymorphism is associated with depression?

A

Single nucleotide change in promotor region of 5HT1A autoreceptors in dorsal ralphe
C/C or C/G
- Less autoreceptor
- High levels of activity and release therefore less depression
G/G
- Enhanced autoreceptor
- Less serotonin activity due to negative feedback
- Insensitivity to antidepressants such as fluoxetine

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13
Q

What are the properties of the receptor 5-HT2A?

A
  • G-coupled receptor which activates PLC
  • Cleaves PIP2 to form IP3 which can cause Ca release
  • Ca and DAG then activate PKC
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14
Q

What is the 5-HT2A receptor implicated in?

A
  • Schizophrenia
  • High levels in neocortex and striatum
  • Agonists are hallucinogens (LSD)
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15
Q

What are the properties of the 5-HT3 receptor?

A
  • Ionotropic, causes depolarisation
  • Found in CNS and PNS in noicireceptive neurons
  • Chemo can cause GI damage, causing release of 5-HT on 5-HT3 receptors causing vomiting
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16
Q

What are the properties of 5-HT1B and 5-HT1D receptors?

A
  • Usually autoreceptors
  • Can create homeostasis, if they sense high ammounts of transmitter in the cleft signal for less release (decrease effect of antidepressants)
17
Q

Give an example of the state dependent effects of serotonin

A
  • Somatogastric ganglion (STG) in crabs is very well studies, contains 30 large neurons
  • Computational monitoring of circuits medulatingn gastric (slow) and pyloric (fast) outputs which compete with eachother
  • Different levels of input from the 2 channels: small differences can have big effects and big differences can have small effects s
18
Q

What is the role of serotonin on the GI tract?

A
  • Enterochromaffin cells produce the most 5-HT
  • Regulates gut motility and vasoconstiction
  • Transmits information on the state of the gut (satiety, pain, nausea)
19
Q

What is the role of serotonin in the smooth muscle?

A

Uterus contracts with increasing concentrations of 5-HT

20
Q

What function does serotonin play in blood platelet aggrgation?

A

Increases with 5-HT secretion from EC cells

21
Q

Where is serotonin secreted from in the brain?

A
  • In small number of ‘raphe’ nuclei found in the midline of the brain
  • As shown by modified rabies virus which can jump synapses they are innervated by most major brain areas
22
Q

What does serotonin regulate in the brain?

A

“Behavioural states” - state which changes how an animal reacts to certain stimuli
Implicated in cognitive processes

23
Q

How are sensory systems modulated by behavioural states?

A
  • Response of neurons to odours changes with serotonin

- Adjusts perception to circumstances e.g hunger

24
Q

How does serotonin modulate vision?

A

Serotonin levels modulare light sensitivity according to circadian rhythms (found through the application of 5HT to locust photoreceptors)

25
Q

What effect does serotonin have on locusts?

A

Behavior and appearance change dependent on whether ‘solitary’ or ‘gregarious’ with more serotonin in ‘gregarious’ state

  • Serotonin activated by mechanosensory stimulation and through the sight/smell of other locusts
  • Application of 5HT antagonists inhibits gregarious state
26
Q

Give an example of 5-HT modulating motor systems

A
  • Zebrafish rythmic movements decrease in frequency with application of 5HT
  • Believed to be involved with monitoring whether behaviour executed is correct, responding to visual axes and choosing the next movement accordingly
27
Q

What role does 5HT have in learned helplessness?

A

Levels decrease when rat left to swim in tank it can’t escape (model of depression-like hopelessness/fatalism)

28
Q

How can depression be linked to 5HT and glucocorticoids?

A
  • Stress induces promotion of glucorticoids
  • downregulates BDNF causing atrophy and decreased cell survival
  • Anti-depressants upregulate NE and 5-HT in order to upregulate BDNF
29
Q

How is the anterior hippocampus required for anxiety behaviour?

A
  • From recording potentials in mice in elevated T maze, found that ventral hippocampus activates mPFC to induce anxiety
  • Inhibition of vHPC caused less anxiety behaviour
30
Q

How does serotonin modulate the anxiety response?

A
  • Application of serotonin dampens mPFC response
  • Same effect when 5-HTB agonist applied (inhibitory autoreceptors)
    Theory - In low 5-HT from dorsal raphe low activation of 5-HTB receptors on vHPC neurons, releases glutamate on PFC causing anxiety
  • In high 5-HT, 5-HTB receptors are filled and inhibit vHPC input on PFC, decreasing anxiety

PN3312 (11 decks)

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