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Neuro-pharmacology > Serotonergic Systems and Receptors > Flashcards

Serotonergic Systems and Receptors Flashcards

1
Q

Seratonergic neurons project from a number of locations in the brainstem and innervate the entire forebrain. Most interesting are located in the

A

raphe nuclei (~165,000 seratonergic cells

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2
Q

Caudal raphe nuclei Seratonergic projections to

A

the cerebellum and descending projections to the spinal cord.

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3
Q

Seratonergic projections to the cerebellum and descending projections to the spinal cord. mediate

A

sensory, motor, and autonomic functions of 5-HT

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4
Q

Rostral raphe nuclei Ventral projections to

A

basal ganglia, substantia nigra, VTA, limbic system and cortex.

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5
Q

Rostral raphe nuclei Dorsal projections to

A

midbrain (tegmentum and tectum).

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6
Q

Rostral raphe nuclei Cerebellar projections to

A

cerebellar cortex and deep cerebellar nuclei

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7
Q

para-chloroamphetamine, MDMA both have

A

neurotoxic effects selectively on seratonergic pathways

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8
Q

MDMA is

A

neurotoxic at high doses or via microinjection

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9
Q

5,7-dihydroxytryptamine (5,7-DHT) is a

A

BBB impermeable selective toxin that can induce robust serotonergic injury

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10
Q

Seratonergic lesions produce

A

deficits in food intake, reproductive behaviour, pain sensitivity, anxiety, learning, memory, and motor function

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11
Q

Microelectrodes implanted into the dorsal raphe nuclei in free moving cats

A

While awake a steady firing pattern is observed Sudden sensory stimulus causes an abrupt cessation of output from the dorsal raphe nuclei

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12
Q

Seratonergic firing patterns in the dorsal raphe suggests

A

activity during repetitive movement, Proposed to suppress sensory processing and facilitate repetitive tasks

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13
Q

5-HT is colloquially thought to contribute to

A

happiness, Antidepressants target 5-HT reuptake and improve mood

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14
Q

5-HT binding capacity has been suggested to correlate with tendency towards

A

spirituality

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15
Q

5-HT1 – GPCR – Gi

A

(↓ cAMP, GIRK)

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16
Q

5-HT2 – GPCR – Gq/11

A

(PLC, ↑ Ca2+)

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17
Q

5-HT3

A

Ligand gated Na+ and K+ channel

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18
Q

5-HT4 – GPCR – Gs

A

(↑ cAMP)

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19
Q

5-HT5 – GPCR – Gi

A

(↓ cAMP , GIRK)

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20
Q

5-HT6 – GPCR – Gs

A

(↑ cAMP)

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21
Q

5-HT7 – GPCR – Gs

A

(↑ cAMP)

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22
Q

5-HT1A Agonists

A

Buspirone, Cannabidiol - partial agonist)

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23
Q

Agonists at 5-HT1A cause

A

hyperphagia

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24
Q

Agonists decrease 5-HT release
Prevents

A

attenuation of appetite

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25
Q

5-HT1A Concentrated in

A

hippocampus, amygdala, and septum

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26
Q

Agonists at 5-Inhibitory neurotransmitter

A

Signals through Giα to inhibit adenylate cyclase
Signals through Gβγ to specialized inhibitory K+-channels (GIRK – G-protein coupled inward rectifying K+-channel)

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27
Q

WAY-100,635

A

Experimental selective 5HT1A receptor agonist

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28
Q

WAY-100,635 used as

A

as a PET ligand to identify 5HT1A receptors in the human brain

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29
Q

Spirituality

A

Proposed 5-HT system was the source of individual variation in spiritual zeal

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30
Q

5-HT1B and 1D

A

Inhibitory through cAMP and GIRK

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31
Q

1B not expressed in

A

humans, instead there are two 1D variants (1Dα and 1Dβ)

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32
Q

5-HT1B and 1D are found

A

on intracranial blood vessels

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33
Q

5-HT1B and 1D Agonists include

A

anti-migraine medicationq

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34
Q

anti-migraine medication

A

Sumatripan (Imitrex) agonized 1B and 1D receptors

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35
Q

Migraine pathogenesis

A

Cortical spreading depression Expanding pulse of activity followed by hypoactivity

36
Q

migraines often originate

A

originates in occipital cortex (causing perception of auras)

37
Q

Migraine pathogenesis - Cortical spreading depression accompanied by

A

constrictions in blood flow

38
Q

Reactive vasodilation causes

A

pain

39
Q

Reactive vasodilation causes pain

A

Sensory fibers release vasodilating peptides
Peptides promote a sterile inflammatory response
Inflammation causes sensitization of sensory fibers of the dura mater and meningeal blood vessels which are well innervated by pain fibers

40
Q

5-HT modulates

A

neuropeptide release

41
Q

5HT1D receptors are

A

inhibitory

42
Q

Agonists of 5HT1D inhibit release of

A

vasodilating peptides

43
Q

Agonists of 5HT1D inhibit release of vasodilating peptides

A

Promotes vasoconstriction rather than vasodilation

44
Q

Agonists of 5HT1D inhibit release of vasodilating peptides
Promotes vasoconstriction rather than vasodilation Leads to

A

decreased excitation of trigeminal nerve and decreased effect on nausea centres

45
Q

5-HT2 receptor family

A

Gqα signal to PLC resulting in increased Ca2+ and PKC activation

46
Q

5-HT2 receptor family Mostly function as

A

postsynaptic receptors

47
Q

5-HT2 receptor family High densities in

A

nucleus accumbens, striatum, cortex (esp. frontal)

48
Q

5HT2A Experimental agonists DOI

A

DOI administration to rodents leads to a characteristic head twitch (brief and periodic)

49
Q

Antagonists of 5HT2A

A

ketanserin, clozapine (Cozaril) and risperadone (Risperdal)

50
Q

ketanserin

A

antihypertensive and useful as a PET radioligand for 5HT2A receptors

51
Q

Atypical antipsychotics

A

clozapine (Cozaril) and risperadone (Risperdal)

52
Q

Psychedelics affecting 5HT2 receptors

A

LSD, mescaline, psilocybin are all agonists at 5HT2 receptors (particularly 5HT2A)

53
Q

5HT2A agonists are considered

A

potent hallucinogens

54
Q

5-HT2B and 2C receptors affect appetite

A

fenfluramine (norfenfluramine) is an agonist for 5-HT2B and 5HT2C (and 2A at sufficient dose)

55
Q

Lorcaserin (Belviq)

A

is a specific agonist for 5-HT2C and anorectic drug in limited use to treat obesity

56
Q

5-HT2C is also expressed in the

A

choroid plexus and regulates CSF composition and volume in response to 5-HT in the CSF

57
Q

5-HT2C in the amygdala is

A

anxiogenic and proposed to be the cause of acute side effects of SSRIs

58
Q

5-HT3 receptors

A

only 5-HT ligand-gated ion channel

59
Q

5HT3 receptors are expressed in the

A

chemoreceptor trigger zone and in the gut

60
Q

Agonists of 5-HT3 receptors are

A

vomit inducing

61
Q

Agonists of 5-HT3

A

2-methyl-5-HT

62
Q

Antagonists of 5-HT3 receptors are

A

anti-emetic

63
Q

Ondasetron (Zofran)

A

is a prescription anti-emetic used to treat chemotherapy-related nausea

64
Q

Subdivisions of the DRN have been implicated in

A

anxiety, panic, and mood disorders

65
Q

anxiety in the Dorsal Raphe nucleus

A

DRN, dorsal part (DRD)
DRN, caudal part (DRC)

66
Q

Panic in the Dorsal Raphe nucleus

A

DRN, ventrolateral (DRVL)
ventrolateral periaqueductal gray (VLPAG)

67
Q

Serotonergic neurons in the DRN are active in response to

A

anxiogenic stimuli

68
Q

Serotonergic neurons in the DRN are active in response to anxiogenic stimuli Anxiogenic agents

A

(caffeine) increase activity

69
Q

Social defeat paradigms increase

A

DRN activity

70
Q

DRD activated in

A

fear-potentiated startle

71
Q

DRC activated by

A

unpredictable noise stress

72
Q

Antidepressants targeting serotonergic neurotransmission are effective

A

anxiolytics

73
Q

Antidepressants targeting serotonergic neurotransmission are effective anxiolytics

A

MAOI, TCA antidepressants are highly effective but with severe side effects

74
Q

Antidepressants targeting serotonergic neurotransmission are effective anxiolytics ones with fewer side effects

A

SSRI and SNRI are effective and well tolerated

75
Q

5-HT depletion (via tryptophan depletion)

A

increases depressive symptoms

76
Q

5-HT1A receptors function primarily as

A

autoreceptors

77
Q

Autoreceptors

A

drive negative feedback to inhibit 5HT release

78
Q

5-HT1A agonists are effective

A

anxiolytics

79
Q

5-HT1A agonists are effective anxiolytics

A

Cannabidiol (5-HT1A partial agonist)
Buspirone (5-HT1A partial agonist)

80
Q

Polymorphisms of the 5-HT1A receptor gene

A

are implicated in risk of depression and anxiety
Predicts poor response to SSRI therapy

81
Q

In the presence of SSRI antidepressants 5-HT is

A

broadly increased

82
Q

In the basolateral amygdala

A

5-HT activates 5-HT2C receptors

83
Q

5-HT2C activation is

A

anxiogenic

84
Q

5-HT2C receptors are

A

downregulated slowly with SSRI use

85
Q

In the basolateral amygdala 5-HT activates 5-HT2C receptors Proposed to play a role in the

A

early anxiety and depression in initial SSRI use

Neuro-pharmacology (26 decks)

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