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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
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

PHS 931 (29 decks)

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