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

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Flashcards in Block 2 Lecture 2 -- DA, 5HT, and Amino Acids Deck (75):
1

What are the 4 major brain DA pathways?

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

2

Describe the anatomy of the mesolimbic pathway.

VTA projects to:
-- NAc
-- HP
-- Amy

3

Describe the anatomy of the mesocortical pathway.

VTA projects to PFc

4

Describe the anatomy of the tuberinfundibular pathway.

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

5

What is the function of the mesocortical pathway?

executive function
-- decision-making
-- impulsivity

6

What is the function of the mesolimbic pathway?

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

7

How do drugs of abuse cause addiction?

increase DA in mesolimbic pathway
-- positive reinforcement, learning/memory, emotional control

8

Describe the anatomy of the nigrostriatal pathway.

Substantia nigra projects to striatum

9

What pathway is affected in PD?

nigrostriatal DA pathway

10

For what conditions are DAr agonists used?

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

11

For what conditions are DAr antagonists used?

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

12

What are the main receptor classes of DAr's?

1) Gs (D1 and D5-like)
2) Gi (D2-, 3, and 4-like)

13

What is the function of D1/D5 Gs receptors?

-- in CNS
-- typically post-synaptic
-- increase cAMP

14

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

-- in CNS
-- pre and postsynatpic (like a2 and M2)
-- decrease cAMP

15

Which DAr is cloned?

D5-like

16

What are the peripheral roles of 5-HT?

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

17

What are the central roles of 5-HT?

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

18

In what conditions is 5-HT dysregulation implicated?

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

19

Where is 5-HT synthesized?

from Trp in Raphe Nucleus

20

How is 5-HT broken down?

1) MAOb
2) synthesized into melatonin

21

Where is melatonin synthesized?

pineal gland

22

Where is serotonin stored?

serotonergic cell groups

23

Where are melatonin receptors located?

1) SCN
2) anterior pituitary
3) periphery

24

What are the 5-HT receptors?

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

25

Where does LSD act?

5HT2 antagonist

26

Where do the triptans act?

5HT1 antagonist
5HT4 agonist

27

Which serotonin receptor is inhibitory?

5HT1 Gi

28

Which serotonin receptor is an LGIC?

5HT3

29

What are the signs/sxs of serotonin syndrome?

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

30

What drugs can cause serotonin syndrome?

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

31

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

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

32

What is the TA pair for glycine?

glyoxylate

33

What is the TA pair for glutamate?

alpha-KG

34

What is the TA pair for Asp?

OAA

35

What is the TA pair for GABA?

succinic-semialdehyde

36

Where does vigabatrin act?

inhibits GABA TA

37

What are the glutamate transporters?

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

38

Why are there so many Glu transporters?

high concentration of Glu as a NT

39

Where are EAAT1 GluTs located?

astrocytes

40

Where are EAAT2 GluTs located?

astrocytes
presynaptic

41

Where are EAAT3 GluTs located?

postsynaptic

42

Where are EAAT4 GluTs located?

postsynaptic

43

What are the predominant neurotransmitters in mammalian brains?

Glu + GABA

44

How are GluR's classified?

1) metabotropic
2) ionotropic

45

What are the metabotropic GluRs?

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

46

What are the ionotropic GluRs?

1) kainic acid
2) AMPAr
3) NMDAr

47

What does NMDA stand for?

n-methyl-D-aspartate

48

What does AMPA stand for?

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

49

Describe the permeability of the kainic acid receptor?

Na

50

Describe the permeability of the AMPAr?

Na

51

Describe the permeability of the NMDAr?

Ca

52

How is the NMDAr activated?

Gly and Glu
-- co-agonists

53

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

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

54

How is the NMDAr modulated?

1) directly by polyamines (spermine) and Zn
2) by increased activity, removing the Mg block

55

What is the function of the NMDAr Mg-block?

decreased activation of the NMDAr

56

Why does GABA have so many receptor subtypes?

highly flexible molecule with many different comformations

57

What are the GABA receptors?

1) GABAa (LGIC)
2) GABAb (Gi)

58

What are the subunits of the GABAa receptor?

many different alpha/beta
-- alpha 1-6
-- beta 1-3
-- wildcard d, e, g, t, pi

59

What are the 5 main domains of the GABAa receptor?

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

Where is the GABA binding site on GABAa?

between a and b

61

Where is the BZD binding site on GABAa?

between a and g

62

What GABAa modulators bind in the channel?

1) barbs
2) steroids
3) picrotoxin

63

What GABAa modulators bind outside the channel?

GABA
BZDs

64

What is a GABAa agonist?

muscimol

65

What is muscimol?

GABAa agonist
-- poison native to KY

66

What are GABAa antagonists?

1) bicucline (competitive)
2) picrotoxin (non-competitive)

67

Describe the GABAb receptor.

metabotropic Gi
-- similar to a2 and M2 (presynaptic to decrease NT release)
-- high [GABAb] in spinal cord

68

What is a GABAb agonist?

baclofen

69

What is baclofen?

GABAb-selective GABAb agonist

70

What is glycine?

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

71

What is a renshaw cell?

interneuron in ventral horn of SC
-- inhibits recurrent activity

72

Describe the glycine receptor, vesicular transport, and reuptake?

similar in structure/fx to GABAa
-- LGIC Cl
-- transported into vesicle via VGLYT
-- reuptake mediated by GLYT

73

Where does glycine bind on the NMDAr?

Gly B-site (strychnine-insensitive binding site)

74

What is a GlyR antagonist?

strychnine

75

What is strychnine?

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