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Cellular Neuroscience > Serotonergic Transmission > Flashcards

Serotonergic Transmission Flashcards

1
Q

What type and subtype of NT is 5-HT?

A

Amine –> indolamine.

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2
Q

What is an indolamine?

A

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

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3
Q

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

A

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

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4
Q

How do we obtain the amino acid tryptophan?

A

Solely from our diet.

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5
Q

How is tryptophan converted into 5-HTP?

A

Tryptophan hydroxylase removes a hydroxyl group from tryptophan.

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6
Q

How is 5-HTP converted into 5-HT?

A

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

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7
Q

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

A

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

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8
Q

How is tryptophan transported into the brain?

A

Actively transported across the BBB.

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9
Q

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

A

Tryptophan hydroxylase.

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10
Q

Which transporter loads 5-HT into vesicles?

A

VMAT (vesicular monoamine transporter).

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11
Q

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

A

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

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12
Q

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

A

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

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13
Q

How many families of 5-HT receptors are there?

A

Seven.
5-HT(1-7).

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14
Q

What are the subtypes of 5-HT(1) receptors?

A

5-HT(1A-1F).

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15
Q

What are the subtypes of 5-HT(2) receptors?

A

5-HT(2A-2C).

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16
Q

What are the subtypes of 5-HT(5) receptors?

A

5-HT(5A-5B).

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17
Q

Which 5-HT receptors are postsynaptic metabotropic receptors?

A

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

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18
Q

Which 5-HT receptors are presynaptic metabotropic receptors?

A

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

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19
Q

Which 5-HT receptors are postsynaptic ionotropic receptors?

A

5-HT(3).

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20
Q

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

A

Somatodendritic autoreceptor.

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21
Q

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

A

Soma and dendrites.

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22
Q

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

A

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

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23
Q

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

A

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

24
Q

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

A

In the intestines.

25
Q

What is the role of intestinal 5-HT?

A

Mediates hormonal, autocrine, paracrine and endocrine functions.

26
Q

What is the peristaltic reflex?

A

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

27
Q

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

A

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

28
Q

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

A

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

29
Q

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

A

IBS has been linked to dysfunctional SERTs in the gut.

30
Q

Where is 5-HT synthesised in the brain?

A

Group of brainstem nuclei called the raphe nuclei.

31
Q

Where do caudal raphe nuclei project to?

A

The spinal cord.

32
Q

Where do rostral raphe nuclei project to?

A

Almost everywhere.

33
Q

What is unipolar depression?

A

Individuals experience episodes of depression only.

34
Q

What is bipolar disorder?

A

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

35
Q

What are the symptoms of mania?

A

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

36
Q

Name three examples of unipolar depression.

A

Major depression.
Postnatal depression.
Seasonal effective disorder.

37
Q

What are affective disorders?

A

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

38
Q

What is the neurological basis of sleep disturbances?

A

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

39
Q

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

A

Abnormalities in various hypothalamic nuclei.

40
Q

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

A

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

41
Q

What is the neurological basis of anxiety?

A

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

42
Q

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

A

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

43
Q

What is the neurological basis of alterations in thought content?

A

Abnormal functioning of the cerebral cortex.

44
Q

Why is it so difficult to treat affective disorders?

A

An overwhelming number of brain structures are involved.

45
Q

What predicts responsiveness to treatment with antidepressant drugs?

A

Increased activity in the anterior cingulate cortex.

46
Q

When is DBS used for depression?

A

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

47
Q

What is the monoamine hypothesis of depression?

A

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

48
Q

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

A

There have widespread projections and a role in antidepressant action.

49
Q

Define antidepressant drugs.

A

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

50
Q

Name the five categories of antidepressant drugs.

A

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

51
Q

Which monoaminergic system has the most massive and diffuse projections?

A

Serotonergic system.

52
Q

Where in the brain is noradrenaline synthesised?

A

In several brainstem nuclei, mainly the locus coeruleus.

53
Q

What is the requirement for effective antidepressants?

A

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

54
Q

How do SRIs act on monoamines?

A

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

55
Q

How do SNRIs act on monoamines?

A

Moderate affinity for both NA and 5-HT transporters.

56
Q

How do MAOIs act on monoamines?

A

Prevent the degradation of all monoamines.

Cellular Neuroscience (10 decks)

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