Serotonin Flashcards
What is the chemical name for serotonin?
5-Hydroxytrypamine (5-HT)
What is the primary role of serotonin?
To regulate blood pressure
Describe the synthesis of 5-HT
It is synthesized from tryptophan, which is found in our diet
- tryptophan gets brought into the brain via a BBB transporter
- Tryptophan is then transformed into 5-hydroxytyrptophan (5-HTP) via tryptophan hydroxylase
- tryptophan needs two cofactors, O2 and BH4 in order to synthesize 5-HTP - 5-HTP gets converted into 5-HT via aromatic amino acid decarboxylase (AADC)
What is the primary method of serotonin signal termination?
Through reuptake via serotonin transporter (SERT)
What is the other method of terminating serotonin’s signal? Name both enzymes and their metabolites.
- it is primarily metabolized by MAO, which transforms 5-HT into 5-HIAA
- in the pineal gland, a different enzyme, 5-HT-N-acetylase converts 5-HT into melatonin
Where are the cell bodies of serotonin neurons primarily located?
In the raphe nucleus
- serotonin projects throughout the brain
What is serotonin implicated in?
Sleep, sexual function, mood, among other things
What are the two types of serotonin neurons found in the raphe nucleus?
Dorsal neurons and median neurons
Describe the dorsal serotonin neurons?
They have fine axons and have very small variscocities (bumps)
Describe the median neurons?
They have larger, more beaded axons
Which drug is a selective SERT reuptake inhibitor?
MDMA (ecstacy)
- this drug increases serotonin release
What do high doses of MDMA cause?
It damages the fine axons of the dorsal 5-HT neurons
Name the serotonin receptors.
- 5-HT1 (1a, 1b, 1d, 1f)
- 5-HT2(2a, 2b, 2c)
- 5-HT3
- 5-HT4 (5-HT5, 5-HT7)
- 5-HT6
Which serotonin receptor is the only one that is ligand-gated?
5-HT3
What is the general net effect of serotonin?
It is modulatory; it controls both excitatory as well as inhibitory responses
What is the hypothesized cause of the positive symptoms of schizophrenia?
There is an excessive amount of dopamine transmission in the ventral striatum
What are the negative and cognitive symptoms of schizophrenia caused by?
both of these symptom clusters arise from not enough dopamine transmission in the prefrontal cortex
Which receptor do all typical antipsychotics effect?
D2 receptors
Where is there a higher concentration of dopamine receptors?
in the dorsal striatum
How do typical antipsychotics work on the dopamine pathways?
Typical antipsychotics block the D2 receptors in all dopamine pathways (pfc, dorsal and ventral striatum), but since there aren’t a lot of receptors found in the PFC, the typical antipsychotics only really alleviate the positive symptoms of schizophrenia effectively)
What is one major downfall of the typical antipsychotics?
They all have very severe side effects (extrapyramidal/parkinsonian side effects)
Why do typical antipsychotics cause parkinsonian like symptoms?
Because there is a good amount of DA in the dorsal striatum, but typical antipsychotics decrease the amount of dopamine transmitted in this area, which equals a negative net effect
Why are typical antipsychotics more likely to produce these negative side effects?
Because in order to be effective, they need a 60-80% occupancy of D2 receptors, which means that the dose required to alleviate symptoms is much higher compared to atypical antipsychotics
Why is one of the effects of taking antipsychotics sedation?
Because they are also histamine antagonists
What is the affinity of atypical antipsychotics?
35-45% occupancy in the dorsal striatum
What is the main difference in the mechanics of atypical antipsychotics vs. typical ones?
Atypical are also 5-HT antagonists, alongside the regular D2R antagonism
How are the negative and cognitive symptoms treated better with atypical antipsychotics?
Because they act as 5-HT antagonists, and 5-HT inhibits the release of DA in the dorsal striatum and PFC, this means that more dopamine is being transmitted in areas where there is a lack; this lack is thought to be the cause of negative and cognitive symptoms of schizophrenia
- they also block D2R receptors in all DA projection pathways, so that dopamine levels overall are more regulated
