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psyc 462 > lecture 11 LOs > Flashcards

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

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2
Q

where else does serotonin exist (besides the raphe nuclues)

A

the gut

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3
Q

is serotonin a monoamine

A

yes, similar to both DA and NE

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4
Q

what is the molecular type of serotonin

A

indolamine

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5
Q

what is serotonin synthesized from

A

the amino acid tryptophan

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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

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7
Q

where can tryptophan be found

A

only in serotonergic neurons

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8
Q

what does para-chlorophenylalnine (PCPA) do

A

irreversibly inhibits tryptophan hydroxylase to block serotonin synthesis

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9
Q

what stimulates serotonin synthesis

A

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

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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

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11
Q

how can the levels of serotonin in humans be temporarily decreased

A

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

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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

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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

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14
Q

what transports serotonin into vesicles

A

VMAT2

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15
Q

what is VMAT2 sensitive to

A

reserpine

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16
Q

what do serotonin autoreceptors on presynaptic terminals do

A

inhibit release

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17
Q

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

A

slows the firing rates of them

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18
Q

after release, how is serotonin removed from the synapse

A

reuptake by the serotonin transporter (SERT)

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19
Q

how is the breakdown of serotonin catalyzed

A

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

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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

psyc 462 (21 decks)

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