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B&B Week 7 Flashcards > Lecture 35: Serotonin > Flashcards

Lecture 35: Serotonin Flashcards

1
Q

What is the mechanism of serotonin synthesis?

A

Serotonin synthesized in cell body
Tryptophan  5-HTP (hydroxytryptophan)  5-HT
-tryptophan is an essential amino acid

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2
Q

What is the characteristic of serotonin?

A

It is involved in many physiological processes, but is not associated with just one!

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3
Q

What is serotonin?

A

5-hydroxytryptamin
8-10% present in platelets
80% in eneterochromaffin cells in GI track (duodenum)
20% produced in CNS

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4
Q

What does serotonin do to platelets?

A

Causes platelet aggregation via actions of 5-HT receptors

  • important in clotting
  • healthy vessels with 5HT lead to vasodilation
  • damaged vessels with 5HT leads to constriction
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5
Q

What does serotonin do in GI tract?

A

Widespread distribution of SERT (serotonin transporter) in gut
Regulations motility and digestion of GI tract
Initiate secretory and peristaltic reflexes

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6
Q

Where is serotonin produced?

A

In nuclei of the midbrain
Primarily in the RAPHE nuclei
Caudal body cell body groups vs. rostral cell body groups

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7
Q

What is the inactivation process of 5-HT?

A

MAO degradation

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8
Q

What is the significance of tryptophan hydroxylase?

A

Rate limiting step

Tryptophan to 5-hydroxyTRYPTOPHAN (not tryptamine)

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9
Q

What is the significance of serotonin in the pineal gland?

A

It is the precursor to melatonin

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10
Q

What is the common byproduct of serotonin?

A

5-HIAA (5 hydroxyindoleacetic acid)

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11
Q

What are the two genes that regulate 5-HT synthesis?

A

By tryptophan hydroxylase periphery (Tph1)
And
Tph2 (in the brain)
Serotonin is regulated SEPARATELY in brain and periphery

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12
Q

What is Tph2 regulated by?

A 
Short term:
-phosphorylation leads to increased enzymatic activity
	-PKA
	-Ca/CamKII
	-PKC
Long term:
-exogenous signals (cAMP) can up or down regulate total amount of protein via gene regulation
	-neural activity
Stress hormones and ovarian steroids
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13
Q

Can you increase/decrease serotonin through diet?

A

Yes you can through taking tryptophan hydroxylase
e.g. spaghetti
(5-HTP) is used as an aid for sleep to increase serotonin

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14
Q

How do you decrease serotonin?

A

Take drink with NEUTRAL amino acids

  • takes away tryptophan
  • decreases serotonin
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15
Q

How is serotonin stored?

A

Serotonin transport (SERT)
-responsible for removal of serotonin from synaptic cleft
-inhibited by SSRIs
-inhibited by fenfluramine
Vesicular monamine transporter 1 and 2
-responsible for vesicular concentration of catecholamines and serotonin
-inhibted by reserpine
-inhibted by fenfluramine
There is some evidence that people with short/short serotonin transporter has a higher risk of developing depression

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16
Q

What does fenfluarmine do? Significance

A 
Blocks VMAT (vesicular monoamine transport) and SERT
-this increases the active extrusion of serotonin
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17
Q

What are antidepressants?

A

Substrates for pre-synaptic transporters

-stimulates RELEASE of serotonin in synapse

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18
Q

What is the significance of increased intracellular 5-HT?

A

Favors release of 5-HT by REVERSE action of the SERT and acts as substrate for SERT to inhibit the transport of 5-HT INTO cells

19
Q

What does MDMA (3,4-methylenedioxy-N-methamphetamine; ecstasy) do?

A

Reverses direction of SERT (so 5-HT now flows OUT and blocks reuptake)

20
Q

Reverses direction of SERT (so 5-HT now flows OUT and blocks reuptake)

A

Reserpine

Fenfluramine

21
Q

What is the difference between Serotonin RELEASERS vs. serotonin TRANSPORT INHIBITOR?

A

Releasing agent releases 5-HT by 10 fold
SSRI releases 5-HT by 4 fold
Releasers = destroy serotonin neurons

22
Q

What are examples of serotonin releasers?

A
  1. PCA (p-chloroamphetamine)
    • neurotoxin that destroys serotonin neurons to release serotonin
  2. Fenfluramine (because 5-HT is released when increased cytoplasmic concentration)
  3. MDMA (reverses SERT)
23
Q

What does MAO (monoamine oxidase) do to serotonin?

A

They cleave 5-HT to 5-HIAA
Also cleaves NE
Encoded for by MAO-A and MAO-B

24
Q

What is the common feature of serotonin receptors?

A 
14 families that are very HETEROGENEOUS
Can be pre synaptic and postsynaptic
5HT2 use calcium
5HT3-7 use cAMP
5HT1 is at presynaptical terminal
25
Q

What is 5-HTT?

A

SERT

Reuptake transporter

26
Q

What are the physiological functions associated with serotonin?

A
  1. Temperature regulation
  2. Sleep
  3. Eating and body weight regulation
  4. Sexual behavior
  5. Pain sensitivity
  6. Aggression
  7. Blood pressure
  8. Respiration
  9. Learning and memory
  10. Depression and anxiety
  11. General behavioral functions
    • behavioral inhibition and impulsivity
    • facilitates spinal motor reflexes
27
Q

What are the medical illnesses associated with serotonin?

A
  1. depression
  2. anxiety
  3. OCD
  4. Schizophrenia
  5. Alzheimer’s
  6. Obesity
  7. Migraine
  8. IBS
  9. Neuroprotection
28
Q

What are examples of SSRIs?

A

Fluoxetine
Sertraline
Paroxetine
Citalopram

29
Q

What is Citalopram?

A

SSRI

30
Q

What is Paroxetine?

A

SSRI

31
Q

What are tricyclic antidepressants?

A

Blocks 5-HTT (SERT) but with more side effects

Unlike SSRI for side effects

32
Q

What is the key characteristic of SSRIs? Reason for popularity?

A
  1. Sertraline and Paroxetine are more SELECTIVE for serotonin than for norepinephrine
    Selectivity = selectivity for serotonin OVER NE
  2. Lack affinity for receptors of other antidepressants
  3. FEWER SIDE EFFECTS
33
Q

What is phenelzine?

A

A MAOI

34
Q

What is Serotonin Syndrome?

A

Over secretion of serotonin
Occurs when SWITCHING among SSRIs or to other drug classes MAOIs)
-potential overactivation of serotonin receptors
Symptoms:
-SYMPATHETIC DISCHARGE
-ab pain, diarrhea,
-sweating, fever,
-tachycardia, increased blood pressure and altered mental state

35
Q

What is trazodone? Significance?

A

SSRI Antidepressant

Has a metabolite m-chlorophenylpeperazin (mCPP) that leads to serotonin syndrome

36
Q

Can you get serotonin syndrome from just SSRI metabolism?

A

Yes

Due to mCPP metabolite from Trazodone

37
Q

What is the half-life of SSRIs? Significance?

A

Fluoxetine can be present WEEKS after you take them off

Need to wait before subscribing next drug because you can get serotonin syndrome if you don’t wash out

38
Q

How does SSRI produce antidepressant effect?

A
  1. increased serotonin in synapse
  2. increased CREB
  3. increased BDNF
  4. increased neurogenesis
39
Q

What’s the difference of depleting serotonin from individual with depression to individual without depression?

A

Individual WITH prior depression will relapse with serotonin depletion
Individual WITHOUT depression will not get depressive symptoms

40
Q

What anxiety disorders are treated with SSRIs?

A
  1. Generalized anxiety disorder
  2. panic disorder
  3. OCD
  4. Social phobia
  5. PTSD
41
Q

What is the mechanism of ANXIOLYTIC effects of SSRIs (reduce anxiety)?

A
  1. Increased serotonin
  2. down regulation of 5-HT2C receptors
  3. Increased GABA release in forebrain regions
    -regulation of GABA-A receptor subunits
  4. Increased production of neurosteroids
    Example: allopregnanolone (sedative effect)
42
Q

What is 5-HT2C? Significance?

A

Stimulation of 5-HT2C leads to ANXIETY
-located in amygdala
Blocked by SSRI

43
Q

How do serotonins help migraines?

A
  1. Increase in 5-HIAA in urin during migraine attack
  2. Reversal of vasodilation
    Sumatriptan in 5-HT1D
  3. Prevention of neuroinflammation
    5-HT2 antagonists (cyproheptadine)
  4. Inhibits CGRP release
    “Calcitonin gene-related peptide)
44
Q

What is sumatriptan?

A

A 5-HT1D agonist that helps with migraine

Lead to vasoconstriction

B&B Week 7 Flashcards (16 decks)

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