Serotonin

Question 0

Why is serotonin called serotonin ?

Answer 0

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

Question 1

What groups make up serotonin ?

Answer 1

Indole group and an amine group

Question 2

Where is serotonin present ?

Answer 2

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

Question 3

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

Answer 3

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

Question 4

What is eosinophilia myalgia ?

Answer 4

Caused by taking dietary supplements of l-tryptophan

Incurable and sometimes fatal neurological syndrome

Question 5

How is serotonin made ?

Answer 5

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

Question 6

How is serotonin stored ?

Answer 6

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

Question 7

After the release of serotonin what happens to it ?

Answer 7

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

Question 8

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

Answer 8

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

Question 9

What effect do SSRIs have on the uptake transporter ?

Answer 9

Prevent the reuptake of serotonin to enhance its effects

E.g reserpine and tetrabenazine

Question 10

What is fenfluramine used for and why ?

Answer 10

Weight control drug

Because increased levels of serotonin rescue appetite

Question 11

What does ecstasy do to the body ?

Answer 11

Inhibits uptake of serotonin in the brain

Causes increased heart beat, emotional high and increased energy levels- euphoria

Question 12

How is serotonin metabolised ?

Answer 12

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

Question 13

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

Answer 13

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

Question 14

What are examples of serotonin neurotoxins ?

Answer 14

5,6- DHT- used in research

5,7-DHT- taken up by SERT

Question 15

What is the purpose of amphetamines in the serotonin system ?

Answer 15

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

Question 16

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

Answer 16

Dorsal periventricular pathway

Ventral tegmental pathway

Question 17

Explain the dorsal paraventricular pathway ?

Answer 17

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

Question 18

Explain the ventral tegmental pathway ?

Answer 18

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

Question 19

Where do the 2 ascending pathways join ?

Answer 19

Caudal hypothalamus forming median forebrain bundle

Question 20

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

Answer 20

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

Question 21

What effect does serotonin have at receptors ?

Answer 21

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

Question 22

What type of receptor is 5-HT3 ?

Answer 22

Only ionotropic ones

Question 23

Describe 5-HT 1 receptors ?

Answer 23

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

Question 24

Explain the 5-HT 1 somatodendritic autoreceptors?

Answer 24

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

Question 25

What is the function of busprione?

Answer 25

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

Question 26

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

Answer 26

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

Question 27

What is LSd?

Answer 27

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

Question 28

Explain the 5-HT1 presynaptic autoreceptors?

Answer 28

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

Question 29

What is sumatriptan ?

Answer 29

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

Question 30

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

Answer 30

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

Question 31

Describe 5-HT 3 receptors

Answer 31

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

Question 32

What is ondansetron ?

Answer 32

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

Question 33

What are the links with serotonin and hunger ?

Answer 33

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

Question 34

What are the links between serotonin and aggression ?

Answer 34

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

Question 35

What is teh predatory aggression pathway ?

Answer 35

Corticomedial nuclei of amygdala to Lateral hypothalamus to Ventral tegmentum

Question 36

What is the affective aggression pathway ?

Answer 36

Basolateral nuclei of amygdala to Lateral hypothalamus to PAG

Question 37

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

Answer 37

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

Question 38

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

Answer 38

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

Question 39

Where is serotonin present in the GIT ?

Answer 39

In the chromaffin cells

Question 40

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

Answer 40

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

Question 41

What is the link between serotonin and neuroendoctrine function ?

Answer 41

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

Question 42

What is the link between serotonin and circadian rhythm ?

Answer 42

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