Serotonin Flashcards
Name a variety of processes which involve serotonin
- Anxiety
- Learning
- Vasoldilaton
- Hunger
- Pain
How does serotonin accomplish its varied functions?
- Processes everywhere in the brain despite only manufactured in a few areas
- Variety of receptors, 7 families with specific localisations and functions
- Transmitted in a variety of ways (one-to-one or bulk transmission)
- State dependent effects
How is serotonin synthesised?
- Is made from an essential amino acid L-Tryptophan
- Undergoes hydrosylation by tryaptophan hydroxylase
(type 1 is non neuronal, type 2 is neuronal) - Then decarboxylated to serotonin by L-aromatic acid decarboxylase
How is serotonin degraded?
- By monoamine oxidase through the substitution of NH2 with OH
- Acted on by aldehyde dehydrogenase to form -COO gorup
- Otherwise addition of glucose where it is processed by the kidneys and excreted
Why does an increased protein diet not necessarily result in higher brain serotonin levels?
- Dietary tryptophan faces competition with other neural amino acids to cross blood brain barrier
- Therefore high protein diet increases competition
How is serotonin released at the synapse?
- Taken into vesicles by transporter VMAT2 where it is then released into the post synaptic cleft
- 5-HT transporters reuptake serotonin from the cleft
How do serotonin depletion drugs work?
Para-chlorophenylamine blocks tryptophan hydroxylase
How do serotonin agonists work?
- SSRIs block serotonin transporters and therefore increase levels in the cleft
- MDMA (para-chloranphetamine) induces synaptic release however this results in a long term depletion of serotonin release
What are the 4 different positions of serotinergic synapses?
- Axo-dendritic (classic)
- Axo-somatic - closer to where the action potential is generated so generating a more significant response
- Axo-axonic - affect only one axon terminal
- Dendro-dendritic - mad shit
What are the properties of 5-HT1A receptors?
- G-coupled
- Inhibits adenyl cyclase, reduced cAMP which inhibits cAMPk
- Enhancement of K+ channels and therefore an inhibitory effect
What are 5-HT1A receptors implicated in?
Anxiety and depression, high levels in hippocampus, amygdala and dorsal raphe nucleus
What polymorphism is associated with depression?
Single nucleotide change in promotor region of 5HT1A autoreceptors in dorsal ralphe
C/C or C/G
- Less autoreceptor
- High levels of activity and release therefore less depression
G/G
- Enhanced autoreceptor
- Less serotonin activity due to negative feedback
- Insensitivity to antidepressants such as fluoxetine
What are the properties of the receptor 5-HT2A?
- G-coupled receptor which activates PLC
- Cleaves PIP2 to form IP3 which can cause Ca release
- Ca and DAG then activate PKC
What is the 5-HT2A receptor implicated in?
- Schizophrenia
- High levels in neocortex and striatum
- Agonists are hallucinogens (LSD)
What are the properties of the 5-HT3 receptor?
- Ionotropic, causes depolarisation
- Found in CNS and PNS in noicireceptive neurons
- Chemo can cause GI damage, causing release of 5-HT on 5-HT3 receptors causing vomiting
What are the properties of 5-HT1B and 5-HT1D receptors?
- Usually autoreceptors
- Can create homeostasis, if they sense high ammounts of transmitter in the cleft signal for less release (decrease effect of antidepressants)
Give an example of the state dependent effects of serotonin
- Somatogastric ganglion (STG) in crabs is very well studies, contains 30 large neurons
- Computational monitoring of circuits medulatingn gastric (slow) and pyloric (fast) outputs which compete with eachother
- Different levels of input from the 2 channels: small differences can have big effects and big differences can have small effects s
What is the role of serotonin on the GI tract?
- Enterochromaffin cells produce the most 5-HT
- Regulates gut motility and vasoconstiction
- Transmits information on the state of the gut (satiety, pain, nausea)
What is the role of serotonin in the smooth muscle?
Uterus contracts with increasing concentrations of 5-HT
What function does serotonin play in blood platelet aggrgation?
Increases with 5-HT secretion from EC cells
Where is serotonin secreted from in the brain?
- In small number of ‘raphe’ nuclei found in the midline of the brain
- As shown by modified rabies virus which can jump synapses they are innervated by most major brain areas
What does serotonin regulate in the brain?
“Behavioural states” - state which changes how an animal reacts to certain stimuli
Implicated in cognitive processes
How are sensory systems modulated by behavioural states?
- Response of neurons to odours changes with serotonin
- Adjusts perception to circumstances e.g hunger
How does serotonin modulate vision?
Serotonin levels modulare light sensitivity according to circadian rhythms (found through the application of 5HT to locust photoreceptors)
What effect does serotonin have on locusts?
Behavior and appearance change dependent on whether ‘solitary’ or ‘gregarious’ with more serotonin in ‘gregarious’ state
- Serotonin activated by mechanosensory stimulation and through the sight/smell of other locusts
- Application of 5HT antagonists inhibits gregarious state
Give an example of 5-HT modulating motor systems
- Zebrafish rythmic movements decrease in frequency with application of 5HT
- Believed to be involved with monitoring whether behaviour executed is correct, responding to visual axes and choosing the next movement accordingly
What role does 5HT have in learned helplessness?
Levels decrease when rat left to swim in tank it can’t escape (model of depression-like hopelessness/fatalism)
How can depression be linked to 5HT and glucocorticoids?
- Stress induces promotion of glucorticoids
- downregulates BDNF causing atrophy and decreased cell survival
- Anti-depressants upregulate NE and 5-HT in order to upregulate BDNF
How is the anterior hippocampus required for anxiety behaviour?
- From recording potentials in mice in elevated T maze, found that ventral hippocampus activates mPFC to induce anxiety
- Inhibition of vHPC caused less anxiety behaviour
How does serotonin modulate the anxiety response?
- Application of serotonin dampens mPFC response
- Same effect when 5-HTB agonist applied (inhibitory autoreceptors)
Theory - In low 5-HT from dorsal raphe low activation of 5-HTB receptors on vHPC neurons, releases glutamate on PFC causing anxiety - In high 5-HT, 5-HTB receptors are filled and inhibit vHPC input on PFC, decreasing anxiety
