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BDS2 OCB > OCB03-2009 DOPAMINE > Flashcards

OCB03-2009 DOPAMINE Flashcards

1
Q

Where are the monoaminergic neurons found in the CNS?

A

Cell bodies in brainstem and basal forebrain with diffuse projections

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2
Q

What is the general function of monoaminergic neurons?

A

Modify effects of major excitatory (glutamate) and inhibitory (GABA) neurotransmitters

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3
Q

What diseases is dopamine implicated in?

A

Schizophrenia

Parkinson’s disease

Restless leg syndrome

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4
Q

What is dopamine a precursor for?

A

Noradrenaline

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5
Q

What dopaminergic pathways are there in the CNS?

A

Nigrostriatal pathway

Mesolimbic pathway

Mesocortical pathway

Tuberoinfundibular pathway

Retina

Olfactory tubercle

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6
Q

Describe the dopaminergic nigrostriatal pathway.

A

From substantia nigra to caudate nucleus/putamen (striatum)

Control of movement

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7
Q

What dopaminergic pathway is compromised in Parkinson’s disease?

A

Nigrostriatal pathway

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8
Q

Describe the mesolimbic pathway.

A

From ventral tegmental area to nucleus accumbens (frontal part of caudate nucleus)

Increases responsiveness to external and internal stimuli

Involved in motivation, motor activity and reward

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9
Q

What dopaminergic pathway is important in drug addiction and positive symptoms of schizophrenia?

A

Mesolimbic pathway

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10
Q

Describe the mesocortical pathway.

A

From ventral tegmental area to frontal cortex

Involved in normal cognition, motivation, emotion

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11
Q

What dopaminergic is dysfunctional in psychoses and ADHD?

A

Mesocortical pathway

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12
Q

Describe the tuberoinfundibular pathway.

A

From arcuate nucleus (in hypothalamus) to the median eminence

Important in control (inhibition) of prolactin release from adenohypophysis

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13
Q

What is the pathway of synthesis of dopamine?

A

L-tyrosine –> L-DOPA by tyrosine hydroxylase

L-DOPA –> dopamine by L-DOPA decarboxylase (aromatic amino acid decarboxylase)

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14
Q

Which enzyme catalyses the reaction L-tyrosine –> L-DOPA?

A

Tyrosine hydroxylase

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15
Q

Which enzyme catalyses the reaction L-DOPA –> dopamine?

A

L-DOPA decarboxylase

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16
Q

What is the pathway of dopamine degradation in neurons?

A

Dopamine –> dihydroxy-phenyl acetic acid (DOPAC) by MAOa/b

DOPAC –> homovanillic acid (HVA) by COMT

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17
Q

What is the final metabolite of dopamine?

A

Homovanillic acid

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18
Q

What does COMT stand for?

A

Catechol-O-methyl transferase

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19
Q

What is the pathway of dopamine degradation in glial cells?

A

Dopamine –> 3-methoxy-tyramine (3MT) by COMT

3MT –> to homovanillic acid by MAOa/b

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20
Q

Where is MAO found?

A

In outer mitochondrial membranes in presynaptic terminal and other cells

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21
Q

What can MAOa metabolise?

A

Dopamine, NA, serotonin

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22
Q

What can MAOb metabolise?

A

Dopamine

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23
Q

Where is COMT found?

A

Extraneuronal, intracellular areas

24
Q

What can be measured to determine dopaminergic brain activity?

A

Homovanillic acid in CSF

25
Describe general dopaminergic transmission.
DA taken up into vesicles by VMAT and stored in an acidic environment AP = DA exocytosed into synaptic cleft DA stimulates post (D1, 2) and pre (D2) synaptic receptors DA leaves by diffusion and is taken up by DAT or ENT to be stored or metabolised
26
Where is DAT found?
Presynaptic neuronal cell membrane
27
Where is ENT found?
Glial cell membrane
28
What does ENT mean?
Extraneuronal transporter
29
What does VMAT mean?
Vesicular monoamine transporter
30
Which type of transporter removes most of the dopamine after transmission?
DAT
31
What are the two main groups of dopamine receptors?
D1 and D2
32
How many dopamine receptors are there in total?
5
33
Which dopamine receptors are part of the D1 family?
D1 D5
34
Which dopamine receptors are part of the D2 family?
D2, 3, 4
35
Which dopamine receptors are the most abundant in the brain?
D1 and D2
36
Which family of dopamine receptors are involved in prolactin secretion?
D2 (D2 and 3)
37
Which dopamine receptors are involved in motor control?
All of them (mostly D1 and D2)
38
Which dopamine receptors are involved in emotion?
All of them (mostly D1 and D2)
39
Which dopamine receptors are involved in arousal and mood?
D1 > D2 > D4
40
What G protein is the D1 receptor family coupled to?
Gs
41
Where are the D1 receptor family mainly found?
Postsynaptically
42
What G protein is the D2 receptor family coupled to?
Gi/o (open K channels)
43
Where are the D2 receptor family found?
Pre and postsynaptically
44
Which receptor family does DA have a higher potency with?
D2
45
What are some dopamine antagonists?
Chlorpromazine Haloperidol Sulpiride Clozapine
46
What are some dopamine agonists?
Apomorphine Bromocripine
47
What are the consequences of degeneration of the nigrostriatal pathway?
(Parkinson's disease) Tremor Akinesia Postural instability Rigidity
48
Why may hyperprolactinaemia be a side effect of D2 antagonists for schizophrenia treatment?
Inhibits the tuberoinfundibular pathway so prolactin release is uncontrolled
49
How does cocaine affect DA transmission and what is the result of this?
Inhibits DAT = increased extracellular DA so increases receptor stimulation Stimulant and addictive; psychoses
50
How does amphetamine and methylphenidate affect DA transmission and what is the result of this?
Increase DA release and inhibit DAT to increase extracellular DA Stimulant and addictive; psychoses Calming in ADHD
51
How does L-DOPA administration affect DA transmission?
Increases DA formation so increased transmission
52
How does selegiline administration affect DA transmission?
Inhibits MAOb so decreased DA metabolism to increase transmission
53
What does entacapone do?
Inhibits COMT to decrease L-DOPA metabolism
54
What drugs can be used to treat Parkinson's disease?
``` (Increases DA transmission) L-DOPA Selegiline Entacapone Apomorphine Rotigotine Ropinirole Pramipexole ```
55
What are the D2 antagonists and what do they treat?
Sulpiride Clozapine Antipsychotics for schizophrenia

BDS2 OCB (22 decks)

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