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Neuropharmacology > Fluoxetine - serotonin system > Flashcards

Fluoxetine - serotonin system Flashcards

1
Q

5-hydroxytryptamine

A

5-HT or serotonin

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2
Q

90% of serotonin found in…

A

gut

enterochromatin cells

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3
Q

10% of 5-HT found in…

A

CNS (mainly mid-brain)

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4
Q

biosynthesis of serotonin

A

tryptophan –> 5-hydroxytryptophan –> 5-hydroxytryptamine

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5
Q

5-HT in diet

A

tryptophan found in meat and dairy products

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6
Q

degradation of 5-HT

A

monoamine oxide enzyme

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7
Q

enzyme in 5-HT biosynthesis

A

tryptophan hydroxylase

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8
Q

how are serotonin receptors classified

A

by their pharmacology and their signal transduction mechanisms

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9
Q

how many 5-HT receptor subtypes

A

7

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10
Q

which 5-HT receptor is an autoreceptor

A

5-HT1

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11
Q

main function of fluoxetine

A

SSRI

blocks serotonin transporter

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12
Q

SSRI stands for

A

serotonin selective re-uptake inhibitor

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13
Q

SERT

A

serotonin transporter

sodium-dependent

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14
Q

importance of SERTs

A

recover neurotransmitter

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15
Q

if you block SERTs

A

you increase bioavailability of serotonin in the synaptic cleft

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16
Q

clinical uses of SSRIs

A

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

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17
Q

common side effects of SSRIs

A

nausea
vomiting
constipation
diarrhoea

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18
Q

time delay in serotonin release

A

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

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19
Q

why is there a time delay in serotonin release

A

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

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20
Q

clinical use of 5-HT modulators

A

treatment of migraines

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21
Q

mechanism of migraine treatment by 5-HT modulator

A

5-HT receptor agonists induce vasoconstriction in cerebrovascular smooth muscle

they do this by inhibiting release of vasoactive peptides

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22
Q

cause of migraine

A

cranial vasodilation

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23
Q

examples of 5-HT receptor agonist

A

triptans

ergot alkaloids

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24
Q

lorcaserin

A

5-HT 2C receptor agonist

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

25
Q

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

A

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

26
Q

2 tests used to evaluate depressive like behaviours in animals

A

forced swim test

sucrose preference test

27
Q

process of forced swim test

A

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

28
Q

what is measured in forced swim test

A

time spent immobile

latency (time until 1st immobility reached)

29
Q

effect of antidepressants on forced swim test

A

rat spends less time immobile and more time swimming

30
Q

3 methods to induce stress upon a rodent

A

restraint
early-life
intruder mechanism

31
Q

tubes in sucrose preference test

A

tube A = water

tube B = water + sucrose

32
Q

method of sucrose preference test

A

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

33
Q

rats self-administration of cocaine

A

rats with cocaine press lever more for more cocaine

34
Q

effect of fluoxetine on self administration of cocaine

A

rats with fluoxetine have less reinforcement

35
Q

progressive ratio test

A

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

36
Q

break point in progressive ratio test

A

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

37
Q

the greater the breakpoint

A

the more motivation the animal has

38
Q

effect of cocaine on breakpoint

A

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

39
Q

which 5-HT receptor is not a 7TM GPCR

A

5-HT3

40
Q

ligand for 5-HT3

A

cation channel
Na+
K+

41
Q

another factor that contributes to serotonin related diseases

A

polymorphisms in the 5-HT receptors

42
Q

5-HT1 signalling pathways

A

Gi/o

decreases cAMP

43
Q

main functions of 5-HT1 signalling

A 
neuronal inhibition
behaviour
sleep
feeding
thermoregulation
anxiety
44
Q

5-HT2 signalling pathways

A

Gq

45
Q

effects of 5-HT2 signalling

A

increased IP3 and DAG and Ca2+

46
Q

main function of 5-HT3 and 5-HT4

A

neuronal excitation

47
Q

5-HT3 receptor type

A

ligand gated ion channel

48
Q

5-HT4 signalling pathway

A

Gs
increased cAMP
stimulatory

49
Q

which 5-HT receptors signal via Gs

A

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

50
Q

transporter to get 5-HT into vesicles

A

VMAT

51
Q

fluoxetine treats

A

major depressive disorder

bulimia nervosa

52
Q

5-HT2 receptor antagonist used to treat hypertension

A

ketanserin

53
Q

5-HT3 receptor antagonists prevent nausea and vomiting

A

ondansetron

tropisetron

54
Q

where are 5-HT2C receptors often located

A

POMC neurons in hypothalamus

55
Q

what is the POMC

A

pro-opiomelanocortin neurons

56
Q

Prader-Willi Syndrome

A

genetic form of obesity

reduced expression of 5-HT2C receptor

57
Q

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

A

mice

Wistar rats
Sprague Dawley rats
Long-Evans rats

squirrel monkeys
rhesus monkeys

58
Q

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

A

5-HT5A

59
Q

which 5-HT receptor is found in vascular smooth muscle

A

5-HT1A

Neuropharmacology (14 decks)

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