Serotonin

Question 1

Synthesis of Serotonin from L-Tryptophan.

• 2 steps.

Which one is the rate-limiting step?

Answer 1

L-Tryptophan——->(via Tryptophan hydroxlase)

—-> L-5-Hydroxytryptophan(5-HTP)——(_Aromatic L-amino acid decarboxylase( AADC)_)

—–>5-Hydrozytryptamine(5-HT;Serotonin).

• Conversion of tryptophan—>5-HT, is the rate-limiting step.

Question 2

Function of Para-chlorophenylamine(PCPA)?

Answer 2

• Blocks 5-HT synthesis,

via irreversibly inhibiting tyrosine hydroxylase.

Question 3

L-tryptophan : amino acid and the blood-brain barrier?

Answer 3

• Ratio determines is serotonin is synthesised or not in the brain.

Question 4

Consequences of a low protein diet,and a high carbohydrate meal?

Answer 4

• increase levels of tryptophan relative to ratio.
• allowing more tryptophan to pass BBB and more serotonin to be made.

Question 5

How is serotonin transported into vesicles?

Function of reserpine?

Answer 5

• Transported via VMAT2( vesicular monoamine transporters).
• Reserpine:
  • blocking VMAT, depletes 5-HT.

Question 6

The difference in function between terminal autoreceptors and somatodendritic autoreceptors?

Answer 6

• Terminal Autoreceptors: inhibit 5-HT release directly.
• Somaticautodendritic autoreceptors:
  • inhibit release indirectly by slowing the rate of neuronal firing.

Question 7

Physiology of MDMA(3,4-methylenedioxymethamphetamine)?

Answer 7

• Stimulates the release of 5-HT.
• Results in:
  • low doses: leading to treatment of chronic PTSD.
  • High doses: leading to neuropsychiatric impairment.

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Question 8

Function of SSRIs and examples?

Function of 5-HT transporters and SERT?

How is 5-HT broken down?

Effects of cocaine and MDMA?

Answer 8

SSRIs: Fluoxetine(prozac)

• block 5-HT transporters and SERT.
  
  • prevents serotonin reuptake.

Broken down via MAO.

• Cocaine and MDMA block SERT but also DA transporters.

Question 9

Function of 5-HT_1A receptors?

Where are these receptors concentrated?

what type of receptors are they in the dorsal and median raphe nuclei?

What are the actions of these receptors?

Answer 9

Function:

• inhibitory, reducing AP potential.

Locations:

• hippocampus, septal area, amygdala, and Dorsal raphe nucleus.

Type of receptor:

• Somatodendritic autoreceptors in the dorsal and median raphe nuclei.

Actions:

• inhibits adenylyl cyclase, reducing cAMP synthesis.
• Increase K+ channel opening leading to membrane hyperpolarisation.

Question 10

What is the function of Buspirone, Ipsapirone and 8-OHDPAT?

Answer 10

• Are 5-HT_1A receptor agonists.
• Antidepressant and anxiolytic.

Question 11

5-HT_2A receptors:

• area of high abundance of these receptors?
• Result of activation?
• Difference in function between LSD and Clozapine and risperidone?

Answer 11

• HIgh abundance within the Cortex.
• Activation:
  • activates phosphoinositide second-messenger system.
  • increase levels of Ca2+ and activates PKC.

LSD:

• Hallucinogenic, stimulates 5-HT_2A receptors.

Clozapine and Risperidone:

• block 5-HT_2A.
• Used to treat schizophrenia, as it also blocks DA receptors.