Serotonergic Neurotransmission

This set of flashcards is designed to aid in the review of key concepts surrounding serotonin and melatonin, their synthesis, function, implications on health, and receptor interactions based on lecture content.

What is the molecular structure of serotonin?

5-hydroxytryptamine (5-HT)

Indole ring structure with a substituted amine group

How is serotonin synthesised?

Tryptophan

• hydroxylated by tryptophan hydroxylase

5-hydroxytryptophan

• decarboxylated by L-aromatic amino acid decarboxylase

Serotonin

How is the biosynthesis of melatonin carried out?

Stimulated by circadian variations

1. Acetyl group is added to serotonin by N-acetyltransferase.

2. N-acetyl serotonin is methylated by 5-hydroxyindole-O-methyltransferase

3. This results in the production of melatonin

What does the 5-HT1A receptor do

• 5-HT1A - autoreceptor on the presynaptic neurone and also postsynaptic receptors (transmitting a signal)

• links to reduced anxiety, and emotional stability

Which receptor type does melatonin primarily act on in the CNS?

Melatonin receptors (MT1 and MT2).

What is the primary metabolic product of serotonin?

5-hydroxyindoleacetic acid (5-HIAA), which is excreted by the kidneys.

Formed via a two-step oxidation process.

What is the role of serotonin transporter protein (SERT)?

It reuptakes serotonin from the synaptic cleft back into the synaptic terminals.

(A polymorphism in the promoter region of the SERT gene can lead to less transcription of the gene and is associated with anxiety)

What type of receptor is 5-HT3?

A ligand-gated ion channel.

What role does melatonin play in relation to cognitive function in Alzheimer's disease?

Melatonin reduces A-beta load and has antioxidant properties. Those with Alzheimers have lower melatonin levels

Which receptor is primarily responsible for serotonin's inhibitory effects on neurotransmitter release?

5-HT1A autoreceptor.

What is the significance of biased agonism in relation to serotonin receptors?

Ligand structure allows selective activation of certain signalling pathways, not all. Each agonist stabilises a different receptor shape, leading to different downstream signals.

It contributes to the psychoactive differences between hallucinogens and non-hallucinogens acting at the same receptor (e.g. 5-HT2A)

What are the major effects of psychedelics on 5-HT2A receptors?

They promote enhanced neuroplasticity and reduce rigid thinking.

How is ATD used as evidence that depletion of neuronal 5-HT may contribute to depression

Acute tryptophan depletion (can be caused by dietary manipulation where remaining tryptophan is used in protein synthesis) leads to reduced serotonin synthesis

leads to increased irritability, aggressiveness and temporary relapse of depressive symptoms from those who have recovered following SSRI treatment

Describe the subtypes of serotonin receptors

All are G-protein coupled receptors, apart from 5-HT3

• 5-HT1 - inhibitory, regulates mood and anxiety.

• 5-HT2 - excitatory, involved in perception and hallucinations.

• 5-HT3 (ion channel) mediates nausea, anxiety and gut function

• 5-HT4 - facilitates gut motility

• 5-HT5 - may have a role in circadian rhythms and cognitive functions.

• 5-HT6 - important in mood and learning (target for depression + Alzheimer’s research)

• 5-HT7 - involved in mood regulation and circadian rhythms

Why are 5-HT4 receptors targets for memory disorder research

They are found in high density in the hippocampus (area of the brain essential for learning and memory)

• activation enhances neurotransmitter release and promotes synaptic plasticity

• this can boost memory performance and consolidation