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Fundamental Neuroscience > Serotonin > Flashcards

Serotonin Flashcards

1
Q

Is serotonin a monoamine or catecholamine?

A

Monoamine

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2
Q

What is the other name given to Serotonin?

A

5-hydroxytryptophan (5-HTP)

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3
Q

What is tryptophan converted into and by what?

A

5-Hydroxtryphtophan by Tryptophan hydroxylase

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4
Q

What does the aromatic amino acid decarboxylase (AADC) convert 5-HTP into?

A

5-HT

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5
Q

What are the two versions of tryptophan hydroxylase and where are they expressed?

A

TPH2 - expressed in serotonergic neurons

TPH1 - expressed by non-neuronal cells e.g. 5-HT secreting cells in the gut

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6
Q

What is the rate limiting step for the synthesis of 5-HT?

A

Conversion of tryptophan into 5-HTP

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7
Q

How does para-chlorophenyl amine block (PCPA) block the synthesis of 5-HT?

A

By irreversibly inhibiting tryptophan hydroxylase

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8
Q

How is tryptophan taken into the body?

A

Through the diet

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9
Q

How do we know that 5-HT plays a role in mood?

A

By manipulating the concentration of 5-HT in the brain. Found that tryptophan depletion in brains of depressed individuals on antidepressants showed a relapse in their symptoms. Shows that serotonergic dedication is dependent on the functioning of the serotonin neurotransmitter system

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10
Q

How is serotonin transported to the vesicles and what can block this transportation?

A

By VMAT2 (vesicular monoamine transporter) and blocked by Reserpine (VMAT blocker) depletes 5-HT which is broken down when not protected in vesicles

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11
Q

What do terminal auto-receptors do?

A

Directly inhibit 5-HT release

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12
Q

What do somatodendritic receptors do?

A

Indirectly inhibit release by showing the rate of neuron firing

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13
Q

What drugs stimulate the release of 5-HT and what family of drugs are their structures related?

(4 marks)

A

Para-chloroamphetamine - mainly used experimentally

Fenfluramine - mainly prescribed for appetite suppression in obese patients

3,4-methylenedioxymethamphetamine (MDMA) - recreational drug

All drug structures relate to amphetamine

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14
Q

Outline the process of inactivation of 5-HT.

A
  • After release, 5-HT rapidly removed from synaptic cleft via reuptake by 5-HT transporter/ SERT
  • Transporters are then blocked by selective serotonin uptake inhibitors (SSRIs) e.g. fluoxetine
  • Breakdown of 5-HT is catalysed by MAO to yield 5-hydroxyindonucleatic acid (5-HIAA)
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15
Q

What nuclei are serotonergic nuclei associated with in the brainstem?

A

Raphe nuclei - dorsal and median raphe nuclei give rise to most of the serotonergic fibres in the forebrain

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16
Q

How many different receptor subtypes are there for 5-HT and which ones are metabotropic?

A

14 different subtypes and all are metabotropic apart from 5-HT3

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17
Q

Where are 5-HT1A receptors found?

A

Located postsynaptically in the forebrain. Concentrated in the hippocampus, septal area, amygdala and dorsal raphe nuclei

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18
Q

What is the function of the 5-HT1A receptor?

3 marks

A

Functions as a somatodendritic autoreceptor in the dorsal and median raphe nuclei.

Reduce cAMP synthesis by inhibiting adenyl cyclase.

Increases the opening of K+ channels and membrane hyper polarization

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19
Q

Name a 5-HT receptor agonist.

A

Buspirone and Ipsapirone (antidepressants)

20
Q

Name a 5-HT receptor antagonist.

A

WAY 100635

21
Q

Where are a large number of 5-HT2A receptors located?

A

Cortex

22
Q

What do 5-HT2A receptors do?

A

Activate phosphoinositide secondary messenger system.

23
Q

What does the phosphoinositide secondary messenger system do?

A

Increases Ca2+ levels in postsynaptic cells and also activates protein kinase c (PKC)

24
Q

Name a 5-HT2A antagonist and agonist.

A

Agonist: DOI (hallucinogenic drugs e.g. LSD)
Antagonist: Ketanserin

25
Q

What drug can block serotonin?

A

Clozapine and risperidone - also block D2 receptors and can be used to treat schizophrenia

26
Q

Name an agonist of 5-HT1B/D and what does it do?

A

Triptans - cause constriction of vessels which eases pain

27
Q

Where are 5-HT3 receptors located?

A

In peripheral terminals of vagus nerve

28
Q

How does chemotherapy and radiation in cancer patients affect receptor 5-HT3 and how are these effects counteracted?

A

Chemotherapy and radiation stimulate release of 5-HT in the gut which stimulates vagal 5-HT3 receptors and induces vomiting. But antagonists i.e. ondansetron counteract nausea and vomiting associated with the cancer treatments

29
Q

What ways has serotonin been studied in humans?

A

Comparing levels of 5-HIAA in CSF or 5-HT levels in postmortem brain regions and comparing that with psychiatric disorders. Or identifying associations between psychiatric disorders and polymorphisms in gens for SERT or serotonergic receptors

30
Q

What can lesions in the serotonergic system lead to?

A

Changes in hunger and eating behaviour, anxiety, pain sensitivity, learning and memory

31
Q

What kind of behaviour can lesions in the cortical areas and subcortical limbic structures lead to?

A

Aggression - both cortical and subcortical limbic areas express many different types of 5-HT receptors

32
Q

What is low serotonergic activity typically associated with?

A

Increased aggression but varies depending on genetic background and drug treatment regimes

33
Q

What are high serotonergic levels typically associated with?

A

Reduced aggressive behaviour

34
Q

What is hypophagia and how are 5-HT receptors implicated in it?

A

A feeling of reduced food intake - hypophagia is produced by 5-HT1B 5HT2C receptor agonists and 5-HT6 antagonist. May lead to development of anti-obesity drugs

35
Q

What is the most common treatment for anxiety disorders?

A

SSRIs - receptor 5-HT1A and partial 5-HT1A agonist buspirone can be prescribed

36
Q

What was found in 5-HT1A knockout in mice?

A

Absence of 5-HT1A receptor in forebrain during early post-natal development showed increased risk of developing anxiety as an adult

37
Q

Expression of which receptors were found to increase anxiety in rodents?

A

5-HT2A/2C agonist m-chlorophenylpiperazine (mCPP)

38
Q

How is serotonin linked to pain?

A

5-HT plays a role in the processing of pain - can produce inhibitory or excitatory modulation

39
Q

How is activation of 5-HT1A receptors in the hippocampus linked to memory impairment?

A

Due to the action of the receptor to hyperpolarise and inhibit post synaptic cells

40
Q

Where are 5-HT4 receptors expressed the most?

A

Basal ganglia and hippocampus

41
Q

What do 5-HT4 receptors do?

A

Depolarise post synaptic cells and have an excitatory effect.

42
Q

What may be a function of partial 5-HT4 agonists?

A

Enhancing memory and learning

43
Q

Where are the highest levels of 5-HT6 receptors found?

  • Sun -
A

In the striatum, nucleus acuumbens and olfactory tubercules

44
Q

What happens when 5-HT6 is activated?

A

Leads to stimulation of cAMP synthesis and in some cells has been shown to increase cell excitability and improve memory

45
Q

What do 5-HT6 antagonists do?

A

Improve performance on novel object recognition tasks and supposedly enhance memory consolidation

Fundamental Neuroscience (19 decks)

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