Stahl's - Serotonin and Psychosis

Question 1

Psychoses associated with more visual hallucinations is the result of which neurotransmitter imbalance?

Answer 1

Serotonin

Question 2

Psychoses associated with more auditory hallucinations is the result of which neurotransmitter imbalance?

Answer 2

Dopamine

Question 3

Synthesis of serotonin begins with what amino acid?

Answer 3

Tryptophan

Question 4

How is serotonin action terminated?

Answer 4

Enzymatically destroyed by monoamine oxidase (MAO) or via presynaptic transport pump, serotonin transporter (SERT)

Question 5

What are the three presynaptic 5HT receptors located on the serotonin neuron itself?

Answer 5

1. 5HT-1A
2. 5HT-1B/D
3. 5HT-2B

Question 6

What is the function of presynaptic 5HT receptors on serotonin neurons?

Answer 6

Regulate presynaptic serotonin neuron directly, especially its firing and how it releases and stores its own serotonin

Question 7

Where are presynaptic 5HT-1A receptors found?

Answer 7

Dendrites and cell bodies of serotonin neurons in the midbrain raphe

Question 8

What is the function of 5HT-1A receptors and what role does this play in regulating the serotonin neuron?

Answer 8

Detects serotonin released from the dendrites;
Causes slowing of neuronal impulse flow through serotonin neuron which leads to a reduction of serotonin released from axon terminal

Question 9

What is the function of 5HT-2B receptors and what role does this play in regulating the serotonin neuron?

Answer 9

Act in opposition to the 5HT-1A receptors by activating the serotonin neuron;
Causes more impulse flow and increased serotonin release from presynaptic terminals

Question 10

Where are presynaptic 5HT-1B/D receptors found on serotonin neurons?

Answer 10

Axon terminals

Question 11

What is the function of 5HT-1B/D receptors and what role does this play in regulating the serotonin neuron?

Answer 11

Act as negative-feedback autoreceptors to detect presence of serotonin;
Causes shutdown of further serotonin release and neuronal impulse flow

Question 12

Are 5HT-1A receptors inhibitory, excitatory, or both?

Answer 12

Inhibitory

Question 13

Where are 5HT-1A receptors frequently localized and what effect does this cause?

Answer 13

On postsynaptic GABA neurons;
Inhibits GABA function on downstream neurotransmitters, facilitating further neurotransmitter release

Question 14

Are 5HT-1B receptors inhibitory, excitatory, or both?

Answer 14

Inhibitory

Question 15

Besides serotonin, on which 4 other presynaptic neurotransmitter neurons’ terminals can 5HT-1B be found as a “heteroreceptor” and what effect does this cause?

Answer 15

1. Norepinephrine; 2. Dopamine; 3. Histamine; 4. Acetylcholine; Inhibits further neurotransmitter release

Question 16

Are 5HT-2A receptors inhibitory, excitatory, or both?

Answer 16

Excitatory

Question 17

How do 5HT-2A receptors promote the release of other neurotransmitters?

Answer 17

As a heteroreceptor on glutamate neurons where they lead to excitatory glutamate release on downstream targets

Question 18

How do 5HT-2A receptors inhibit the release of other neurotransmitters?

Answer 18

As a heteroreceptor on GABA interneurons that innervate glutamate neurons, stimulate further GABA release on those glutamate neurons which stops the “neurotransmitter chain” from going downstream

Question 19

Are 5HT-2C receptors inhibitory, excitatory, or both?

Answer 19

Excitatory

Question 20

As postsynaptic heteroreceptors, where are 5HT-2C receptors mostly present?

Answer 20

GABA interneurons

Question 21

What is the net effect of 5HT-2C action?

Answer 21

Stimulates GABA release which leads to net inhibitory effects

Question 22

Are 5HT-3 receptors inhibitory, excitatory, or both?

Answer 22

Excitatory

Question 23

As postsynaptic heteroreceptors, where are 5HT-3 receptors mostly present?

Answer 23

GABA interneurons

Question 24

How does serotonin attaching to postsynaptic 5HT-3 receptors modulate further serotonin output?

Answer 24

When located on GABA interneurons that innervate glutamate neurons, which in turn innervate serotonin neurons

Question 25

Are 5HT-7 receptors inhibitory, excitatory, or both?

Answer 25

Excitatory

Question 26

5HT-7 receptors generally inhibit the release of what neurotransmitter at the cortical level?

Answer 26

Glutamate (via GABA interneurons)

Question 27

What is the function of 5HT-7 receptors within the brainstem raphe nuclei when serotonin release is high?

Answer 27

Via a recurrent collateral from the serotonin neuron that is activated when serotonin release is high, which loops backwards to innervate a GABA neuron with 5HT-7 receptors, which in turn innervates the original serotonin neuron cell body

Question 28

Which serotonin receptor is hypothesized to play a key role in psychosis?

Answer 28

5HT-2A

Question 29

What is hypothesized by the dopamine hypothesis linked to hallucinations and delusions?

Answer 29

Dopamine hyperactivity at D2 receptors in the mesolimbic/mesostriatal pathway, which extends from the VTA/mesostriatum integrated hub to the ventral striatum

Question 30

What is hypothesized by the glutamate hypothesis linked to hallucinations and delusions?

Answer 30

NMDA receptor hypoactivity at GABAergic interneurons with loss of GABAergic inhibition in the prefrontal cortex

Question 31

What is hypothesized by the serotonin hypothesis linked to hallucinations and delusions?

Answer 31

Serotonin hyperactivity/imbalance at 5HT-2A receptors on glutamate neurons in the cerebral cortex

Question 32

How are the dopamine, glutamate, and serotonin hypotheses linked to hallucinations and delusions linked?

Answer 32

Actions of both the serotonin and glutamate hypothesized pathways can lead to downstream dopamine hyperactivity in the mesolimbic pathway