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Flashcards in Serotonin Deck (43):
0

What groups make up serotonin ?

Indole group and an amine group

1

Why is serotonin called serotonin ?

Because it was found in blood serum during clotting
"Ser" for it being in serum
"Tonin" for its vascular effects

2

Where is serotonin present ?

As a neurotransmitter in PNS and CNS
As a local hormone in peripheral vascular system

90% is in the wall of the intestine
In blood
Only 1-2% in the CNS - midbrain
Also in pineal gland as it is a precursor melatonin

3

What amino acid can be converted into serotonin and how do we get it?

Tryptophan
L-tryptophan is the only substance in normal diet
Found in bananas, milk and chocolate

4

What is eosinophilia myalgia ?

Caused by taking dietary supplements of l-tryptophan
Incurable and sometimes fatal neurological syndrome

5

How is serotonin made ?

L-tryptophan converted by L-tryptophan -5-mo oxygenase tryptophan hydroxylase to 5-hydroxy-L-tryptophan
Then it's converted to serotonin by 5-hydroxytryptophan decarboxylase

6

How is serotonin stored ?

Stored on small clear vesicles in presynaptic vesicle
25% is in ready releasable pool
75% is in storage pool

7

After the release of serotonin what happens to it ?

Taken up by the nerve terminal by SERT transporter which is dependent upon sodium gradient and have a 12 transmembrane domain
Protonated serotonin, sodium ion and chloride ion bind to the transporter and induces a conformational ch age causing serotonin molecule to be inserted into cytoplasm
Potassium ion in the cytoplasm binds to the tranpsorter to reorient ate the transporter

8

What is the effect of P-chloroamphetamine and fenfluramine on the uptake transporter ?

They can bind to it and cause the release of any serotonin in the cytosol

9

What effect do SSRIs have on the uptake transporter ?

Prevent the reuptake of serotonin to enhance its effects
E.g reserpine and tetrabenazine

10

What is fenfluramine used for and why ?

Weight control drug
Because increased levels of serotonin rescue appetite

11

What does ecstasy do to the body ?

Inhibits uptake of serotonin in the brain
Causes increased heart beat, emotional high and increased energy levels- euphoria

12

How is serotonin metabolised ?

Converted to 5-HIA by MAO
5-HIA converted to 5-HIAA by aldehyde dehydrogenase
5-HIAA is excreted in CSF
Serotonin can also be converted to melatonin by methylation or acetylation

13

Is MAO-A or MAO-B more effective at metabolising. Serotonin and which is present in serotonin neurones ?

MAO-A is more effective yet MAO-B is present in serotonergic neurones

14

What are examples of serotonin neurotoxins ?

5,6- DHT- used in research
5,7-DHT- taken up by SERT

15

What is the purpose of amphetamines in the serotonin system ?

Act as highly selective serotonin neurotoxins following chronic admin of PCA, fenfluramine and ecstasy

16

What are the 2 main ascending serotonergic pathways from midbrain raphe nuclei ?

Dorsal periventricular pathway
Ventral tegmental pathway

17

Explain the dorsal paraventricular pathway ?

From dorsal raphe nuclei
Mainly innervate striatum, inferior/superior colliculi
Courses its way to forebrain and sends projections to neocortex
Axons are very fine and have small pleomorphic variscocities

18

Explain the ventral tegmental pathway ?

From median raphe nuclei
Innervates hippocampus, septum, hypothalamus, basal ganglia, diencephalon, midbrain and Cortez
Courses it way to forebrain and sends projections to neocortex
Axons are large with no variscocities

19

Where do the 2 ascending pathways join ?

Caudal hypothalamus forming median forebrain bundle

20

What are the 3 important descending serotonergic pathways to the spinal cord ?

These are caudal to the ascending pathways
1- from raphe Magnus nucleus to laminae 1+2 of dorsal horn
2- from raphe obscurus nucleus to laminae 9 of ventral horn
3- from raphe pallidus to intermediolateral cell column

21

What effect does serotonin have at receptors ?

Has both inhibitory and excitatory effects, it depends on the receptors present

22

What type of receptor is 5-HT3 ?

Only ionotropic ones

23

Describe 5-HT 1 receptors ?

1a,b,d,e and f
Coupled to either Gi or Go G protein
Causes inhibition of cAMP formation
Leading to hyperpolarisation mediated by GIRK channels - activation increases potassium efflux
Located pre or post synaptically -autoreceptor on pre

24

Explain the 5-HT 1 somatodendritic autoreceptors?

5-HT1a receptors are mainly autoreceptors present on somata and dendrites
Stimulation reduces firing rate in serotonergic neurons - probably does this by hyper polarising the cell via GIRK channels

25

What is the function of busprione?

It is a 5-HT 1a partial agonist
Used to treat generalised anxiety disorders

26

What is the function of lysergic acid diethylamide (LSD) ?

Acts on 5-HT1a autoreceptors causing potent inhibition of firing an decreasing release of serotonin

27

What is LSd?

Potent hallucinogenic
Most commonly used hallucinogenic
Nearly always taken orally but nowadays found in form of small squares of paper called blotters

28

Explain the 5-HT1 presynaptic autoreceptors?

5-HT 1b and 1d
Control synthesis and release of serotonin but don't influence firing rate therefore they don't affect GIRK channels but actually decrease amount of calcium so decrease release
- could decrease calcium influx by inhibiting adenylate Cyclase

29

What is sumatriptan ?

Non selective 5-HT 1b/d receptor agonist
Used to alleviate migraines

30

How does sumatriptan relieve migraines and what other drugs are also used ?

Migraines are thought to be caused by dilation of extracranial blood vessels so sumatriptan constricts the dilated vessels and relives the headache
- zolmitriptan, donitriptan and almotriptan

31

Describe 5-HT 3 receptors

Ionotropic
Present in CNS: hippocampus, entorhinal cortex, nucleus of solitary tract and area postrema
Present in PNS: pre and post ganglionic autonomic neurons
Activation causes depolarisation by influx of sodium and calcium and efflu of potassium

32

What is ondansetron ?

Selective 5-HT 3 receptor antagonist
Anti-emetic agent against drug induced radiation and vomiting

33

What are the links with serotonin and hunger ?

Increased levels of serotonin reduce your appetite fenfluramine is used to control weight by suppressing appetite but SSRIs such as fluoxetine have the opposite effect by increasing cravings of carbs
It is thepathwaybto the hypothalamus that has been implicated

34

What are the links between serotonin and aggression ?

Reduced levels have been linked to violence and suicide
Low levels of 5-HIAA in CSF have been seen in depressed patients and those with aggressive and impulsive behaviours

35

What is teh predatory aggression pathway ?

Corticomedial nuclei of amygdala to
Lateral hypothalamus to
Ventral tegmentum

36

What is the affective aggression pathway ?

Basolateral nuclei of amygdala to
Lateral hypothalamus to
PAG

37

What are the links between serotonin and depression/OCD/anxiety ?

Depression is treated its SSRIs to increase serotonin levels
OCD is treated with SSRIs or tricyclics antidepressants

38

What is the link between serotonin and sleep-wake cycle ?

Sleep onset is reduced by taking tryptophan which is why it is a good thing to take milk before bed

39

Where is serotonin present in the GIT ?

In the chromaffin cells

40

Why is it important to have sufficient tryptophan in your diet ?

Because it has to be taken up by a transporter to cross the BBB but leucine also uses this transporter and therefore they have to compete for it

41

What is the link between serotonin and neuroendoctrine function ?

Involved in controlling release of hormones from the hypothalamus which controls release from pituitary gland
May also affect anterior pituitary and adrenal cortex

42

What is the link between serotonin and circadian rhythm ?

Suprachiasmatic nucleus maintains the electro physiological outputs which repeat every 24hours and it receives a dense Input from serotonergic neurons
Serotonin is also involved in modulating light effects which will contribute to circadian rhythms