Fluoxetine - serotonin system

Question 1

5-hydroxytryptamine

Answer 1

5-HT or serotonin

Question 2

90% of serotonin found in…

Answer 2

gut

enterochromatin cells

Question 3

10% of 5-HT found in…

Answer 3

CNS (mainly mid-brain)

Question 4

biosynthesis of serotonin

Answer 4

tryptophan –> 5-hydroxytryptophan –> 5-hydroxytryptamine

Question 5

5-HT in diet

Answer 5

tryptophan found in meat and dairy products

Question 6

degradation of 5-HT

Answer 6

monoamine oxide enzyme

Question 7

enzyme in 5-HT biosynthesis

Answer 7

tryptophan hydroxylase

Question 8

how are serotonin receptors classified

Answer 8

by their pharmacology and their signal transduction mechanisms

Question 9

how many 5-HT receptor subtypes

Answer 9

7

Question 10

which 5-HT receptor is an autoreceptor

Answer 10

5-HT1

Question 11

main function of fluoxetine

Answer 11

SSRI

blocks serotonin transporter

Question 12

SSRI stands for

Answer 12

serotonin selective re-uptake inhibitor

Question 13

SERT

Answer 13

serotonin transporter

sodium-dependent

Question 14

importance of SERTs

Answer 14

recover neurotransmitter

Question 15

if you block SERTs

Answer 15

you increase bioavailability of serotonin in the synaptic cleft

Question 16

clinical uses of SSRIs

Answer 16

treat disorders such as depression, general anxiety, OCD, PTSD, social anxiety, bulimia

Question 17

common side effects of SSRIs

Answer 17

nausea
vomiting
constipation
diarrhoea

Question 18

time delay in serotonin release

Answer 18

therapeutic effect of SSRI not seen until several weeks later
then significant increase in serotonin seen

Question 19

why is there a time delay in serotonin release

Answer 19

inhibitory pre-synaptic receptors
auto-receptor decreases 5-HT release however eventually decreases with more treatment
once desensitised then increase in 5-HT seen

Question 20

clinical use of 5-HT modulators

Answer 20

treatment of migraines

Question 21

mechanism of migraine treatment by 5-HT modulator

Answer 21

5-HT receptor agonists induce vasoconstriction in cerebrovascular smooth muscle

they do this by inhibiting release of vasoactive peptides

Question 22

cause of migraine

Answer 22

cranial vasodilation

Question 23

examples of 5-HT receptor agonist

Answer 23

triptans

ergot alkaloids

Question 24

lorcaserin

Answer 24

5-HT 2C receptor agonist

activation of the receptor suppresses appetite –> potential obesity therapy?

Question 25

why are rats mostly used in evalutating depressive behaviours in pre-clinical studies

Answer 25

they are better than mice as they are less anxious around humans

Question 26

2 tests used to evaluate depressive like behaviours in animals

Answer 26

forced swim test | sucrose preference test

Question 27

process of forced swim test

Answer 27

rats in container full of water swim around until they become immobile --> state of despair more time in immobility --> more depressive rat

Question 28

what is measured in forced swim test

Answer 28

time spent immobile | latency (time until 1st immobility reached)

Question 29

effect of antidepressants on forced swim test

Answer 29

rat spends less time immobile and more time swimming

Question 30

3 methods to induce stress upon a rodent

Answer 30

restraint early-life intruder mechanism

Question 31

tubes in sucrose preference test

Answer 31

tube A = water | tube B = water + sucrose

Question 32

method of sucrose preference test

Answer 32

if the rodent is more depressed it will have less preference for sucrose if a stressed animal is given an anti-depressant, its sucrose preference will icnrease

Question 33

rats self-administration of cocaine

Answer 33

rats with cocaine press lever more for more cocaine

Question 34

effect of fluoxetine on self administration of cocaine

Answer 34

rats with fluoxetine have less reinforcement

Question 35

progressive ratio test

Answer 35

number of times you have to press the lever for the reward increases each time

Question 36

break point in progressive ratio test

Answer 36

when the reward isnt worth the effort of pressing the lever that many times

Question 37

the greater the breakpoint

Answer 37

the more motivation the animal has

Question 38

effect of cocaine on breakpoint

Answer 38

animal never reaches breakpoint increased reinforcement rats keep pressing lever until exhaustion

Question 39

which 5-HT receptor is not a 7TM GPCR

Answer 39

5-HT3

Question 40

ligand for 5-HT3

Answer 40

cation channel Na+ K+

Question 41

another factor that contributes to serotonin related diseases

Answer 41

polymorphisms in the 5-HT receptors

Question 42

5-HT1 signalling pathways

Answer 42

Gi/o | decreases cAMP

Question 43

main functions of 5-HT1 signalling

Answer 43

``` neuronal inhibition behaviour sleep feeding thermoregulation anxiety ```

Question 44

5-HT2 signalling pathways

Answer 44

Gq

Question 45

effects of 5-HT2 signalling

Answer 45

increased IP3 and DAG and Ca2+

Question 46

main function of 5-HT3 and 5-HT4

Answer 46

neuronal excitation

Question 47

5-HT3 receptor type

Answer 47

ligand gated ion channel

Question 48

5-HT4 signalling pathway

Answer 48

Gs increased cAMP stimulatory

Question 49

which 5-HT receptors signal via Gs

Answer 49

5-HT4 5-HT5 5-HT6 5-HT7

Question 50

transporter to get 5-HT into vesicles

Answer 50

VMAT

Question 51

fluoxetine treats

Answer 51

major depressive disorder | bulimia nervosa

Question 52

5-HT2 receptor antagonist used to treat hypertension

Answer 52

ketanserin

Question 53

5-HT3 receptor antagonists prevent nausea and vomiting

Answer 53

ondansetron | tropisetron

Question 54

where are 5-HT2C receptors often located

Answer 54

POMC neurons in hypothalamus

Question 55

what is the POMC

Answer 55

pro-opiomelanocortin neurons

Question 56

Prader-Willi Syndrome

Answer 56

genetic form of obesity | reduced expression of 5-HT2C receptor

Question 57

specific types of animals used to evaluate depressive-like behaviours in pre-clinical drug studies

Answer 57

mice Wistar rats Sprague Dawley rats Long-Evans rats squirrel monkeys rhesus monkeys

Question 58

potentiation of which 5-HT receptor modulates exploratory behaviour of rodents

Answer 58

5-HT5A

Question 59

which 5-HT receptor is found in vascular smooth muscle

Answer 59

5-HT1A