Serotonin

Question 1

What is the chemical name for serotonin?

Answer 1

5-Hydroxytrypamine (5-HT)

Question 2

What is the primary role of serotonin?

Answer 2

To regulate blood pressure

Question 3

Describe the synthesis of 5-HT

Answer 3

It is synthesized from tryptophan, which is found in our diet

1. tryptophan gets brought into the brain via a BBB transporter
2. 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
3. 5-HTP gets converted into 5-HT via aromatic amino acid decarboxylase (AADC)

Question 4

What is the primary method of serotonin signal termination?

Answer 4

Through reuptake via serotonin transporter (SERT)

Question 5

What is the other method of terminating serotonin’s signal? Name both enzymes and their metabolites.

Answer 5

1. it is primarily metabolized by MAO, which transforms 5-HT into 5-HIAA
2. in the pineal gland, a different enzyme, 5-HT-N-acetylase converts 5-HT into melatonin

Question 6

Where are the cell bodies of serotonin neurons primarily located?

Answer 6

In the raphe nucleus

- serotonin projects throughout the brain

Question 7

What is serotonin implicated in?

Answer 7

Sleep, sexual function, mood, among other things

Question 8

What are the two types of serotonin neurons found in the raphe nucleus?

Answer 8

Dorsal neurons and median neurons

Question 9

Describe the dorsal serotonin neurons?

Answer 9

They have fine axons and have very small variscocities (bumps)

Question 10

Describe the median neurons?

Answer 10

They have larger, more beaded axons

Question 11

Which drug is a selective SERT reuptake inhibitor?

Answer 11

MDMA (ecstacy)

- this drug increases serotonin release

Question 12

What do high doses of MDMA cause?

Answer 12

It damages the fine axons of the dorsal 5-HT neurons

Question 13

Name the serotonin receptors.

Answer 13

• 5-HT1 (1a, 1b, 1d, 1f)
• 5-HT2(2a, 2b, 2c)
• 5-HT3
• 5-HT4 (5-HT5, 5-HT7)
• 5-HT6

Question 14

Which serotonin receptor is the only one that is ligand-gated?

Answer 14

5-HT3

Question 15

What is the general net effect of serotonin?

Answer 15

It is modulatory; it controls both excitatory as well as inhibitory responses

Question 16

What is the hypothesized cause of the positive symptoms of schizophrenia?

Answer 16

There is an excessive amount of dopamine transmission in the ventral striatum

Question 17

What are the negative and cognitive symptoms of schizophrenia caused by?

Answer 17

both of these symptom clusters arise from not enough dopamine transmission in the prefrontal cortex

Question 18

Which receptor do all typical antipsychotics effect?

Answer 18

D2 receptors

Question 19

Where is there a higher concentration of dopamine receptors?

Answer 19

in the dorsal striatum

Question 20

How do typical antipsychotics work on the dopamine pathways?

Answer 20

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)

Question 21

What is one major downfall of the typical antipsychotics?

Answer 21

They all have very severe side effects (extrapyramidal/parkinsonian side effects)

Question 22

Why do typical antipsychotics cause parkinsonian like symptoms?

Answer 22

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

Question 23

Why are typical antipsychotics more likely to produce these negative side effects?

Answer 23

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

Question 24

Why is one of the effects of taking antipsychotics sedation?

Answer 24

Because they are also histamine antagonists

Question 25

What is the affinity of atypical antipsychotics?

Answer 25

35-45% occupancy in the dorsal striatum

Question 26

What is the main difference in the mechanics of atypical antipsychotics vs. typical ones?

Answer 26

Atypical are also 5-HT antagonists, alongside the regular D2R antagonism

Question 27

How are the negative and cognitive symptoms treated better with atypical antipsychotics?

Answer 27

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