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PHS 931 > Block 2 Lecture 2 -- DA, 5HT, and Amino Acids > Flashcards

Block 2 Lecture 2 -- DA, 5HT, and Amino Acids Flashcards

1
Q

What are the 4 major brain DA pathways?

A

1) nigrostriatal
2) mesolimbic
3) mesocortical
4) tuberinfundibular

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2
Q

Describe the anatomy of the mesolimbic pathway.

A

VTA projects to:

    • NAc
    • HP
    • Amy
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3
Q

Describe the anatomy of the mesocortical pathway.

A

VTA projects to PFc

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4
Q

Describe the anatomy of the tuberinfundibular pathway.

A

arcuate nucleus of HT projects to median eminence; median eminence projects to AP to decrease PRL release

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5
Q

What is the function of the mesocortical pathway?

A

executive function

    • decision-making
    • impulsivity
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6
Q

What is the function of the mesolimbic pathway?

A

1) positive reinforcement
2) learning/memory
3) emotional control

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7
Q

How do drugs of abuse cause addiction?

A

increase DA in mesolimbic pathway

– positive reinforcement, learning/memory, emotional control

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8
Q

Describe the anatomy of the nigrostriatal pathway.

A

Substantia nigra projects to striatum

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9
Q

What pathway is affected in PD?

A

nigrostriatal DA pathway

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10
Q

For what conditions are DAr agonists used?

A

1) PD
2) ADHD
3) hyper-PRL
4) RLS

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11
Q

For what conditions are DAr antagonists used?

A

1) anti-emetics
2) anti-psychotics
3) movement disorders (Huntingtons, Tourettes, dystonias)

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12
Q

What are the main receptor classes of DAr’s?

A

1) Gs (D1 and D5-like)

2) Gi (D2-, 3, and 4-like)

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13
Q

What is the function of D1/D5 Gs receptors?

A
    • in CNS
    • typically post-synaptic
    • increase cAMP
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14
Q

What is the function of D2/3/4-like Gi receptors?

A
    • in CNS
    • pre and postsynatpic (like a2 and M2)
    • decrease cAMP
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15
Q

Which DAr is cloned?

A

D5-like

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16
Q

What are the peripheral roles of 5-HT?

A

1) platelet aggregation (storage granules of platelets)
2) peristalsis, n/v (enterochromaffin)
3) blood vessels and cardiac valves

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17
Q

What are the central roles of 5-HT?

A

1) mood
2) appetite
3) sleep
4) n/v
5) nociception

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18
Q

In what conditions is 5-HT dysregulation implicated?

A

1) migraine
2) anxiety
3) schizophrenia
4) depression
5) n/v
6) aggression/hostility
7) OCD/phobias

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19
Q

Where is 5-HT synthesized?

A

from Trp in Raphe Nucleus

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20
Q

How is 5-HT broken down?

A

1) MAOb

2) synthesized into melatonin

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21
Q

Where is melatonin synthesized?

A

pineal gland

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22
Q

Where is serotonin stored?

A

serotonergic cell groups

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23
Q

Where are melatonin receptors located?

A

1) SCN
2) anterior pituitary
3) periphery

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24
Q

What are the 5-HT receptors?

A

1) 5HT1 (A,B,D) Gi
2) 5HT2 (A,B,D) Gq
3) 5HT3 LGIC
4) 5HT4 Gs

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25
Q

Where does LSD act?

A

5HT2 antagonist

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26
Q

Where do the triptans act?

A

5HT1 antagonist

5HT4 agonist

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27
Q

Which serotonin receptor is inhibitory?

A

5HT1 Gi

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28
Q

Which serotonin receptor is an LGIC?

A

5HT3

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29
Q

What are the signs/sxs of serotonin syndrome?

A

1) diarrhea
2) euphoria
3) drowsiness/dizziness
4) rapid eye movement and muscle contraction
5) hyperthermia
6) shivering, seizures
7) arrhythmia
8) loss of consciousness, death

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30
Q

What drugs can cause serotonin syndrome?

A

1) SSRIs
2) MAOIs
3) TCAs
4) triptans

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31
Q

For what reasons weren’t AAs accepted as NTs until 1980?

A

1) metabolic role
2) distribution
3) high concnetration
4) non-mammalian origin

32
Q

What is the TA pair for glycine?

A

glyoxylate

33
Q

What is the TA pair for glutamate?

A

alpha-KG

34
Q

What is the TA pair for Asp?

A

OAA

35
Q

What is the TA pair for GABA?

A

succinic-semialdehyde

36
Q

Where does vigabatrin act?

A

inhibits GABA TA

37
Q

What are the glutamate transporters?

A

1) EAAT1
2) EAAT2
3) EAAT3
4) EAAT4

38
Q

Why are there so many Glu transporters?

A

high concentration of Glu as a NT

39
Q

Where are EAAT1 GluTs located?

A

astrocytes

40
Q

Where are EAAT2 GluTs located?

A

astrocytes

presynaptic

41
Q

Where are EAAT3 GluTs located?

A

postsynaptic

42
Q

Where are EAAT4 GluTs located?

A

postsynaptic

43
Q

What are the predominant neurotransmitters in mammalian brains?

A

Glu + GABA

44
Q

How are GluR’s classified?

A

1) metabotropic

2) ionotropic

45
Q

What are the metabotropic GluRs?

A

1) Group 1 Gq
- - 1,5
2) Group 2 Gi
- - 2,3
3) Group 3 Gi
- - 4,6,8,7

46
Q

What are the ionotropic GluRs?

A

1) kainic acid
2) AMPAr
3) NMDAr

47
Q

What does NMDA stand for?

A

n-methyl-D-aspartate

48
Q

What does AMPA stand for?

A

alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

49
Q

Describe the permeability of the kainic acid receptor?

A

Na

50
Q

Describe the permeability of the AMPAr?

A

Na

51
Q

Describe the permeability of the NMDAr?

A

Ca

52
Q

How is the NMDAr activated?

A

Gly and Glu

– co-agonists

53
Q

What are non-competitive antagonists of the NMDAr and where do they bind?

A

1) PCP/phencyclidine
2) ketamine
3) DM
4) memantine
- - bind in the channel

54
Q

How is the NMDAr modulated?

A

1) directly by polyamines (spermine) and Zn

2) by increased activity, removing the Mg block

55
Q

What is the function of the NMDAr Mg-block?

A

decreased activation of the NMDAr

56
Q

Why does GABA have so many receptor subtypes?

A

highly flexible molecule with many different comformations

57
Q

What are the GABA receptors?

A

1) GABAa (LGIC)

2) GABAb (Gi)

58
Q

What are the subunits of the GABAa receptor?

A

many different alpha/beta

    • alpha 1-6
    • beta 1-3
    • wildcard d, e, g, t, pi
59
Q

What are the 5 main domains of the GABAa receptor?

A

1) Cl- channel
2) GABA binding site
3) BZD binding site
4) barb/EtOH binding site
5) neurosteroid/volatile anesthetic binding site

–also: picrotoxin-binding site

60
Q

Where is the GABA binding site on GABAa?

A

between a and b

61
Q

Where is the BZD binding site on GABAa?

A

between a and g

62
Q

What GABAa modulators bind in the channel?

A

1) barbs
2) steroids
3) picrotoxin

63
Q

What GABAa modulators bind outside the channel?

A

GABA

BZDs

64
Q

What is a GABAa agonist?

A

muscimol

65
Q

What is muscimol?

A

GABAa agonist

– poison native to KY

66
Q

What are GABAa antagonists?

A

1) bicucline (competitive)

2) picrotoxin (non-competitive)

67
Q

Describe the GABAb receptor.

A

metabotropic Gi

    • similar to a2 and M2 (presynaptic to decrease NT release)
    • high [GABAb] in spinal cord
68
Q

What is a GABAb agonist?

A

baclofen

69
Q

What is baclofen?

A

GABAb-selective GABAb agonist

70
Q

What is glycine?

A

the main NT of renshaw cells in the vental horn of the spinal cord
– co-agonist of NMDAr

71
Q

What is a renshaw cell?

A

interneuron in ventral horn of SC

– inhibits recurrent activity

72
Q

Describe the glycine receptor, vesicular transport, and reuptake?

A

similar in structure/fx to GABAa

    • LGIC Cl
    • transported into vesicle via VGLYT
    • reuptake mediated by GLYT
73
Q

Where does glycine bind on the NMDAr?

A

Gly B-site (strychnine-insensitive binding site)

74
Q

What is a GlyR antagonist?

A

strychnine

75
Q

What is strychnine?

A

GlyR antagonist

    • proconvulsant rat poison
    • emetic response in humans
    • does not act on Gly B-site of NMDAr

PHS 931 (29 decks)

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