Serotonin

Question 1

____________ are a group of NTs/hormones that share a common single AMINE functional group.

Answer 1

monoamines

Question 2

90% of the 5HT in your body is found in the ______.

Answer 2

gut

Question 3

5-HT is a major NT in the _________________ and is released by ______________ cells.

Answer 3

enteric nervous system; enterochromaffin

Question 4

5HT stimulates ________ and secretion into the intestines.

Answer 4

peristalsis

Question 5

5HT is massively released in response to chemical, physical, and pathological stimuli and can activate __________ __________ to signal the brain in generation of nausea & act at the ________ ___________ (chemoreceptor trigger zone).

Answer 5

vagal afferents; area postrema

Question 6

What is the area postrema?

Answer 6

chemoreceptor trigger zone

Question 7

________ _______________ is transported into the brain where it is converted to 5HT by _______ _____________.

Answer 7

dietary L-tryptophan; tryptophan hydroxylase

Question 8

What is the rate limiting enzyme in the production of 5HT?

Answer 8

tryptophan hydroxylase

Question 9

5HT is deaminated by ____________ ___________ to _______________ ____________ in the cytoplasm of _____________ neurons.

Answer 9

monoamine oxidase; 5-hydroxyindoleacetic acid; serotonergic

Question 10

In contrast to the catecholamines, 5HT breakdown occurs only through ________.

Answer 10

MAO

Question 11

Describe the enzymes and pathway of 5HT synthesis and catabolism

Answer 11

L-tryptophan –tryptophan hydroxylase–> 5-HTP –decarboxylase–> 5HT –MAO–> 5-HIAA

Question 12

REVIEW slide 5 diagram

Answer 12

slide 5

Question 13

_________________ (__________) is used in animals to rapidly deplete 5HT.

Answer 13

para-chlorophenylalanine (PCPA)

Question 14

TRUE or FALSE: PCPA is a reversible antagonist of tryptophan hydroxylase.

Answer 14

FALSE: irreversible inhibitor

Question 15

PCPA is an irreversible inhibitor of ________________.

Answer 15

tryptophan hydroxylase

Question 16

1-2 doses of PCPA depletes 5HT by up to _____% for up to ___ weeks.

Answer 16

90; 2

Question 17

______________ also depletes 5HT by inhibiting VMAT.

Answer 17

reserpine

Question 18

Tryptophan can be depleted in humans by administering an amino acid mix devoid of ____________.

Answer 18

tryptophan

Question 19

How does an amino acid mix devoid of tryptophan deplete tryptophan in humans?

Answer 19

• boost of AAs triggers protein synthesis in liver, depleting previous supply of tryptophan
• neutral AAs compete for BBB transporters

Question 20

Which substances can be used for tryptophan/5HT depletion? What is the mechanism?

Answer 20

• PCPA - irreversible inhibitor of tryptophan hydroxylase
• reserpine - inhibit VMAT
• AA mix w/o tryptophan - protein synthesis depletes previous supply of tryptophan

Question 21

TRUE or FALSE: tryptophan-containing mixture will lead to a more sad mood, in comparison to a tryptophan-free mixture

Answer 21

FALSE: no tryptophan = more sad

Question 22

review sllide 8 diagram

Answer 22

slide 8

Question 23

What are some 5-HT releasers? What are they typically used for?

Answer 23

• fenfluramine - weight loss in obesity
• para-chloroamphetamine - experimental amphetamine analogue
• 3,4-methylenendioxymethamphetamine (MDMA) - psychoactive recreational drug (Ecstasy)

Question 24

TRUE or FALSE: fenfluramine is a 5HT depleter

Answer 24

FALSE: 5HT releaser

Question 25

Which 2 NTs are directly opposed in regulating appetite?

Answer 25

dopamine and 5HT

Question 26

How does dopamine regulate appetite?

Answer 26

- stimulate appetite - released in response to food stimuli (smell)

Question 27

How does 5HT regulate appetite?

Answer 27

- decrease appetite - released in response to eating - inhibits dopamine release

Question 28

___________________ suppresses appetite through effects on catecholamines (psychostimulant like amphetamine)

Answer 28

phentermine

Question 29

__________ came into use in the 1990s as an off-label prescription for obesity.

Answer 29

Fen-Phen (fenfluramine-phentermine)

Question 30

Why is phentermine used with fenfluramine in treating obesity?

Answer 30

co-treatmen avoided DROWSINESS and ADVERSE MOOD effects associated with fenfluramine

Question 31

review graph on slide 11

Answer 31

slide 11

Question 32

TRUE or FALSE: Fen-Phen is FDA approved for weight loss

Answer 32

FALSE: never FDA approved

Question 33

What severe adverse consequences are linked with long-term Fen-Phen use?

Answer 33

- heart valve abnormalities - primary pulmonary hypertension - increased BP between heart and lungs (often fatal)

Question 34

Both fenfluramine and dexfenfluramine removed from clinical used in late __________.

Answer 34

1997

Question 35

What class of transporters is responsible for inactivation of 5HT signalling by reuptake?

Answer 35

5HT transporters (SERT)

Question 36

SERT is similar to _____ and ________.

Answer 36

DAT; NAT

Question 37

TRUE or FALSE: many drugs jave effects at all 3 transporters (SERT, DAT, NET)

Answer 37

TRUE

Question 38

SERT also found in __________, ___________, and _____________.

Answer 38

lungs, placenta, platelets

Question 39

SERT pumps systemic 5HT into ___________.

Answer 39

platelets

Question 40

TRUE or FALSE: SERT functions in clotting cascades as a vasodilator.

Answer 40

FALSE: vasoconstrictor

Question 41

TRUE or FALSE: SERT is a popular drug target

Answer 41

TRUE

Question 42

Which drug classes target SERT? Which ones are selective/non-selective?

Answer 42

- TCA antidepressants (non-selective for SERT, NET) - SSRI antidepressants (selective for SERT) - SNRI antidepressants (non-selective for SERT, NET) - SNDRI antidepressants (SERT~NET>DAT) - psychoactive drugs (non-selective for SERT, NET, DAT)

Question 43

What class of drugs does imipramine belong to?

Answer 43

TCA antidepressants

Question 44

What class of drugs does fluoxetine belong to?

Answer 44

SSRI antidepressants

Question 45

What class of drugs does venlafaxine belong to?

Answer 45

SNRI antidepressants

Question 46

What class of drugs do cocaine, amphetamines, MDMA belong to?

Answer 46

psychoactive drugs