lecture 11 LOs Flashcards

1
Q

where are serotonergic neurons in the CNS found

A

along the midline of the brain stem associated with the raphe nuclei

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

where else does serotonin exist (besides the raphe nuclues)

A

the gut

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

is serotonin a monoamine

A

yes, similar to both DA and NE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is the molecular type of serotonin

A

indolamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is serotonin synthesized from

A

the amino acid tryptophan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are the steps of the synthesis of serotonin

A

tryptophan hydroxylase converts tryptophan to 5-hydroxyl-tryptophan (5-HTP) (rate limiting step)
aromatic amino acid decarboxylase (AADC) converts 5-HTP to serotonin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

where can tryptophan be found

A

only in serotonergic neurons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what does para-chlorophenylalnine (PCPA) do

A

irreversibly inhibits tryptophan hydroxylase to block serotonin synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what stimulates serotonin synthesis

A

administration of large doses of precursor (either tryptophan or 5-HTP)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how easily does tryptophan get across the blood brain barrier

A

it competes with other amino acids for transport across the BBB
the ratio of tryptophan determines the stimulation of serotonin synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how can the levels of serotonin in humans be temporarily decreased

A

giving an amino acid ‘cocktail’ without the tryptophan in it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what does the tryptophan reducing cocktail do (how does it work?)

A

it decreases the concentration of tryptophan which decreases the amount of serotonin that can be made
it stimulates synthesis of proteins in the liver which also reduces levels of plasma tryptophan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what does reducing tryptophan through the cocktail result in

A

reappearance of symptoms in previously depressed patients
behavioural changes like increased impulsivity in healthy subjects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what transports serotonin into vesicles

A

VMAT2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is VMAT2 sensitive to

A

reserpine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what do serotonin autoreceptors on presynaptic terminals do

A

inhibit release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what do somatodendritic autoreceptors (on raphe central bodies) do to serotonin neurons

A

slows the firing rates of them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

after release, how is serotonin removed from the synapse

A

reuptake by the serotonin transporter (SERT)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

how is the breakdown of serotonin catalyzed

A

by MAO (mono amine oxidase) to make 5-HIAA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what 5-HIAA used as

A

a measure in the CSF for the activity of serotonin neurons

21
Q

what does fenfluramine do

A

enhances serotonin release via amphetamine like mechanisms
supresses appetite

22
Q

what does MDMA do

A

enhance serotonin release via amphetamine like mechanisms
low controlled doses can be beneficial in PTSD

23
Q

what does MDMA work on

A

DAT and NET but higher affinity for SERT

24
Q

what do SSRIs like fluoxetine do

A

selective serotonin reuptake inhibitor

25
Q

how many serotonin receptors are there

A

at least 14

26
Q

where does the serotonin receptor 5-HT1A reside

A

postsynaptically: in forebrain regions
somato-dendritic autoreceptor: on the cell bodies in the raphe nucleus. inhibits cAMP and/or increases the opening of K+ channels

27
Q

what is a serotonin receptor 5-HT1A agonist and antagonist

A

full agonist: 8-OHDPAT
partial agonist: buspirone
antagonist: WAY-100635

28
Q

what do serotonin 5-HT1B and 5-HT1D receptors do

A

serve as presyanptic autoreceptor on serotonin terminal

29
Q

where is serotonin receptor 5-HT2A found and what does it do

A

distributed widely in cortex and in striatum/nucleus accumbens
activates phosphoinositide second messenger system (inc ca2+ levels and activates protein kinase C)

30
Q

what is a serotonin receptor 5-HT2A agonist and antagonist

A

agonist: DOI. hallucinogenic in humans
antagonist: ketanserin

31
Q

how to investigate serotonin function in humans

A

compare CSF levels of 5-HIAA or postmortem 5-HT/5-HIAA levels w behavioural traits or neuropsychiatric disorders
assess responses to SSRIs or receptor agonists/antagonists
correlate psychiatric disorders and genetic polymorphisms of SERT or 5-HT receptors

32
Q

how to investigate serotonin function in animals

A

lesion serotonin neurons with selective neurotoxins
genetically engineer KO mice lacking certain serotonin receptors or delete the enzyme that makes serotonin

33
Q

which serotonin medications and receptors reduce food intake

A

SSRIs or 5-HT1B or 5-HT2C

34
Q

how do serotonin medications like SSRIs and serotonin receptors like 5-HT1B or 5-HT2C reduce food intake

A

reducing amount of food consumer per meal (but not number of meals)
shift food preference away from fatty foods

35
Q

what do serotonin receptor 5-HT1A agonists do

A

stimulate somatodendritic autoreceptors which reduces serotonin release, leading to hyperphagia (over eating/lack of satiety)

36
Q

what can serotonin receptors do to anxiety

A

regulate it in opposing manners

37
Q

how do h-HT1A agonists do to anxiety

A

reduce it

38
Q

how do h-HT1A KO mice react to elevated plus maze

A

increased anxiety

39
Q

effects of 5-HT1A agonist on reducing anxiety happens where

A

postsynaptically

40
Q

activation of other postsynaptic serotonin receptors (with 5-HT2A/2C agonists) does what to anxiety like beh

A

increases it

41
Q

what do 5-HT2A/2C KO mice show

A

reduced anxiety

42
Q

what is low serotonin activity associated with

A

increased aggression

43
Q

what do 5-HT1A/1B agonists do to aggressive beh in mice

A

decrease it
due to action on post synaptic receptors

44
Q

depletion of what can cause aggression in humans in lab test

A

tryptophan

45
Q

what is an assay for impulsivity in mice

A

light flahses, rat presses L lever, light does not flash rat presses R lever
during the intertrial, the rat must not press any levers

46
Q

what do 5-HT selevtive lesions impair

A

waiting
does this by increse premature responses

47
Q

what do 5HT2C antagonists do

A

impair impulsivity

48
Q

what do 5-HT2C agonists do

A

reduce impulsivity