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Serotonin is synthesized from ___________
Tryptophan
Tryptophan is obtained from _________
diet protein
Gut —> Tryptophan —> _____ (via TPH2) —> 5-HT (via ______)
5-HTP, AADC
What is used as a serotonergic neuron marker?
TPH2
What is the rate limiting step in serotonin synthesis?
TPH2
What prevents tryptophan from passing through the BBB into the brain?
Large amino acid competitors
How can 5-HTP aid in tryptophan passing through the BBB into the brain?
5-HTP does not have to go through TPH2 which is rate limiting
90% of tryptophan is converted to __________ pathway during stress.
kynurenine
How is kynurenine synthesized?
Tryptophan —> Stress stimulates IDO —> kynurenine
What can 5-HT be converted into which explains the connection of sleepiness?
Melatonin
What is a commonality between catecholamine and serotonin synthesis?
AADC
AADC converts _____ and _____ to serotonin and dopamine.
5-HTP, DOPA
Why is dopamine not created with AADC conversion in serotonin synthesis?
DOPA is not the precursor in serotonin synthesis, 5-HTP is
What neurotransmitters do VMAT2 package into vesicles?
Serotonin, dopamine, and norepinephrine
Serotonin _________ is stimulated from drugs like MDMA (“ecstasy”)
release
Serotonin release can be inhibited by which two things?
Autoreceptors (negative feedback loop)
Dendrite autoreceptor activation
What is SERT responsible for?
Reuptake of 5-HT
What is MAO responsible for?
Metabolizing serotonin
What would happen to serotonin levels if we agonized autoreceptors?
Decrease serotonin and increase negative feedback loop
What would happen to serotonin levels if we antagonized autoreceptors?
Increase serotonin and decrease negative feedback loop
What would happen to serotonin levels if we agonized SERT?
Decrease serotonin and increase reuptake
What would happen to serotonin levels if we antagonized SERT?
Increase serotonin and decrease reuptake
______ increases serotonin
MDMA
What are the 3 ways MDMA increases serotonin levels?
Interfering with VMAT2 packaging of serotonin into vesicles
Antagonism of SERT
Agonism of 5-HT receptors
Serotonergic neurons are found in _______ nuclei
raphe
90-95% of serotonin in the body is found in the _____
gut
Serotonin receptors are ___________
metabotropic
There are _________ of serotonin receptor.
more than one type
What happens when serotonin binds with a receptor?
Hyperpolarization with K+ efflux and effects on gene expression
Increase aggression, increase impulsivity, increase compulsivity, and decrease social behaviors are all effects of _______ serotonin.
decreasing
Decreasing anxiety is an effect of ________ serotonin.
increasing
Decrease in ____ in knockout mice caused increased aggression.
TPH2
Increase in _____ caused decreased anxiety and more time in _______ over cliff in mice.
5-HT, open-arm