Serotonergic Transmission

Question 1

What type and subtype of NT is 5-HT?

Answer 1

Amine –> indolamine.

Question 2

What is an indolamine?

Answer 2

Tryptophan-derived specialised metabolites belonging to the indole alkaloids group.

Question 3

What are the four similarities between 5-HT and catecholamines?

Answer 3

Closely related functions.
Shared mechanisms of clearance from synapses.
Shared metabolic pathways.
Jointly targeted by psychomotor stimulants, tricyclic antidepressants, MAOIs, and SSRIs.

Question 4

How do we obtain the amino acid tryptophan?

Answer 4

Solely from our diet.

Question 5

How is tryptophan converted into 5-HTP?

Answer 5

Tryptophan hydroxylase removes a hydroxyl group from tryptophan.

Question 6

How is 5-HTP converted into 5-HT?

Answer 6

5-HTP decarboxylase removes a carboxyl group from 5-HTP.

Question 7

Describe the process of 5-HT removal from the synapse.

Answer 7

Reuptake into terminal via SERT (serotonin transporter).
Enzymatic degradation by MAO.

Question 8

How is tryptophan transported into the brain?

Answer 8

Actively transported across the BBB.

Question 9

What is the rate-limiting enzyme for 5-HT biosynthesis?

Answer 9

Tryptophan hydroxylase.

Question 10

Which transporter loads 5-HT into vesicles?

Answer 10

VMAT (vesicular monoamine transporter).

Question 11

How can drugs alter levels of 5-HT in the brain?

Answer 11

Drugs, e.g. PCPA, can irreversibly inhibit TPH to produce a long-lasting depletion of 5-HT in the brain.

Question 12

How can diet alter levels of 5-HT in the brain?

Answer 12

A low-tryptophan diet can lead to a dramatic reduction in blood tryptophan levels and a substantial reduction of 5-HT in the brain.

Question 13

How many families of 5-HT receptors are there?

Answer 13

Seven.
5-HT(1-7).

Question 14

Which 5-HT receptors are postsynaptic metabotropic receptors?

Answer 14

5-HT(1E-1F) and 5-HT(2A-2C).

Question 15

Which 5-HT receptors are presynaptic metabotropic receptors?

Answer 15

5-HT(1A), 5-HT(1B) and 5-HT(1D).

Question 16

Which 5-HT receptor is a postsynaptic ionotropic receptor?

Answer 16

5-HT(3).

Question 17

What specific type of receptor is 5-HT(1A)?

Answer 17

Somatodendritic autoreceptor.

Question 18

Where in a neuron is 5-HT(1A) found?

Answer 18

Soma and dendrites.

Question 19

Which two 5-HT receptors regulate the synthesis and release of 5-HT?

Answer 19

5-HT(1A).
5-HT(1D).

Question 20

In which six regions of the brain is 5-HT receptor expression high?

Answer 20

Cortex.
Nucleus accumbens.
Striatum.
Hippocampus.
Substantia nigra.
VTA.

Question 21

Where is the majority of the body’s 5-HT produced?

Answer 21

In the intestines.

Question 22

What is the role of intestinal 5-HT?

Answer 22

Mediates hormonal, autocrine, paracrine and endocrine functions.

Question 23

What is the peristaltic reflex?

Answer 23

Mechanical stimulation of the sensory neurons results in the simultaneous activation of both excitatory and inhibitory motor neurons.

Question 24

What is the role of excitatory motor neurons in the peristaltic reflex?

Answer 24

Cause contraction of the circular muscles behind the bolus, propelling it along the GI tract.

Question 25

What is the role of inhibitory motor neurons in the peristaltic reflex?

Answer 25

Cause relaxation of the circular muscles in front of the bolus, allowing it to pass unimpeded.

Question 26

Why are drugs targeting 5-HT transmission often used to treat IBS?

Answer 26

IBS has been linked to dysfunctional SERTs in the gut.

Question 27

Where is 5-HT synthesised in the brain?

Answer 27

Raphe nuclei.

Question 28

Where do caudal raphe nuclei project to?

Answer 28

The spinal cord.

Question 29

Where do rostral raphe nuclei project to?

Answer 29

Almost everywhere.

Question 30

What is unipolar depression?

Answer 30

Individuals experience episodes of depression only.

Question 31

What is bipolar disorder?

Answer 31

Individuals experience at least one episode of mania as well as depression.

Question 32

What are the symptoms of mania?

Answer 32

Feelings of happiness and creativity. Experiencing loss of appetite, insomnia, rapid speech and irritability.

Question 33

Name three examples of unipolar depression.

Answer 33

Major depression. Postnatal depression. Seasonal affective disorder.

Question 34

What are affective disorders?

Answer 34

Characterised by disturbances in mood rather than disturbances in thought or cognition.

Question 35

What is the neurological basis of sleep disturbances?

Answer 35

Alterations in brainstem monoamine or cholinergic nuclei. Disruptions in the suprachiasmatic nucleus (SCN) of the hypothalamus.

Question 36

What is the neurological basis of changes in appetite and energy?

Answer 36

Abnormalities in various hypothalamic nuclei.

Question 37

What is the neurological basis of depressed mood, anhedonia or mania?

Answer 37

Opposing abnormalities in the nucleus accumbens, medial prefrontal cortex, or amygdala.

Question 38

What is the neurological basis of anxiety?

Answer 38

Abnormalities in the functioning of the amygdala and bed nucleus of the stria terminalis (BNST).

Question 39

What is the neurological basis of the release of stress hormones?

Answer 39

Hyperfunctioning of the paraventricular nucleus (PVN). Hyperfunctioning of the amygdala, which activates the PVN.

Question 40

What is the neurological basis of alterations in thought content?

Answer 40

Abnormal functioning of the cerebral cortex.

Question 41

Why is it so difficult to treat affective disorders?

Answer 41

An overwhelming number of brain structures are involved.

Question 42

What predicts responsiveness to treatment with antidepressant drugs?

Answer 42

Increased activity in the anterior cingulate cortex.

Question 43

When is DBS used for depression?

Answer 43

When patients do not respond to drugs, psychotherapy or electroconvulsive therapy.

Question 44

What is the monoamine hypothesis of depression?

Answer 44

Most drug treatments for depression act on targets within monoaminergic synapses, enhancing transmission by NA, 5-HT or both.

Question 45

Why are monoaminergic systems thought to play an important role in the pathophysiology of affective disorders?

Answer 45

They have widespread projections and a role in antidepressant action.

Question 46

Define antidepressant drugs.

Answer 46

A heterogeneous group of compounds that are effective in the treatment of depression.

Question 47

Name the five categories of antidepressant drugs.

Answer 47

Tricyclic. Selective serotonin reuptake inhibitors (SSRIs). Selective noradrenaline reuptake inhibitors (NRIs). Serotonin and noradrenaline reuptake inhibitors (SNRIs). Monoamine oxidase inhibitors (MAOIs).

Question 48

Which monoaminergic system has the most massive and diffuse projections?

Answer 48

Serotonergic system.

Question 49

Where in the brain is noradrenaline synthesised?

Answer 49

In several brainstem nuclei, mainly the locus coeruleus.

Question 50

What is the requirement for effective antidepressants?

Answer 50

They enhance release and/or availability, or prevent the degradation of monoamines.

Question 51

How do SRIs act on monoamines?

Answer 51

High selectivity for the 5-HT transporter. Weak affinity for the NA transporter.

Question 52

How do SNRIs act on monoamines?

Answer 52

Moderate affinity for both NA and 5-HT transporters.

Question 53

How do MAOIs act on monoamines?

Answer 53

Prevent the degradation of all monoamines.