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IDT Fall > Lec 2: Major Central NTs > Flashcards

Lec 2: Major Central NTs Flashcards

1
Q

What are the four conditions to consider a chemical messenger a neurotransmitter?

A

-present in pre-synaptic terminals
-released from pre-synaptic terminal
-when administered into body the effects are identical to the mimicked NT inside body
-should be able to mimic the action of the drug with appropriate affinities and order of potency

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2
Q

list the examples of “small-molecule” NTs

A

acetylcholine, norepinephrine, dopamine, and serotonin

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3
Q

list the examples of “amino acid” NTs

A

y-aminobutyric acid/GABA, glutamate, and glycine

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4
Q

list the examples of “neuroactive peptide” NTs

A

opioid peptides

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5
Q

T/F endocannabinoids are synthesized as needed and stored when not needed

A

false, not stored

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6
Q

*Memorize NT release, action, inactivation on slide 7

A

.

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7
Q

T/F ACh is the neurotransmitter at all vertebrate neuromuscular junctions

A

true

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8
Q

T/F ACH is the NT for all preganglionic neurons, parasympathetic postganglionic neurons, and sympathetic preganglionic neurons

A

False, only all preganglionic neurons and parasympathetic postganglionic neurons

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9
Q

ACh is used within CNS circuits for what processing?

A

cognitive processing of attention, learning, memory, and arousal

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10
Q

define a projection neuron

A

neurons that connect two or more different regions

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11
Q

what is the name of the two projections in the basal forebrain cholinergic
complex that are critical for attention, learning, and memory?

A

ms medial septal nucleus
bas nucleus basilis

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12
Q

Alzheimer’s is associated with changes in what pathway?

A

the septo-hippocampal pathway

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13
Q

what drug class can increase the rate of Alzheimer’s? what do they do? examples?

A

Muscarinic receptor antagonist
disrupt short-term memory
scopolamine and atropine

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14
Q

what two transporters become harder for the neurons to detect due to Alzheimer’s?

A

ChT and VACht

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15
Q

Which drug class is FDA approved to treat symptoms of Alzheimer’s? Examples?

A

cholinesterase inhibitors
Galantamine, Rivastigmine, and Donepezil

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16
Q

The Two major Neuronal nicotinic ACh receptor subtypes are?
what do they do?

A

(a4)2, (B2)3 ->increased cation permeability (Na+, K+)
and
(a7)5 -> increased cation permeability (Ca2+)

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17
Q

what are the three critical components of the SNARE complex and what does it help to control?

A

Synaptobrevin/VAMP, Syntaxin and SNAP-25
Docking and Fusion of Pre-synaptic Vesicles

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18
Q

what are the three catecholamines used in the brain?

A

norepinephrine, dopamine, and epinephrine

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19
Q

all catecholamines in the brain are synthesized from?

A

tyrosine

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20
Q

what contains all machinery for neurotransmitter synthesis, storage and release and are points of synaptic contact (known as swellings along the axon)

A

varicosities

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21
Q

the catecholamines in the CNS regulate what functions?

A

arousal, mood, and central regulation of blood pressure

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22
Q

what is the Locus ceruleus?
what does it target?

A

a nucleus of the brain stem with ascending and descending projections
cerebral cortex, hippocampus, thalamic nuclei, cerebellum and spinal cord

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23
Q

The Locus ceruleus projections to spinal cord are
thought to be important in?

A

regulation and processing of perceptual information (e.g. pain)

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24
Q

Lateral tegmental noradrenergic neurons: what are the two things it is important for?

A

arousal and action of antidepressant drugs

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25
Q

what is the rate limiting step of central noradrenergic neurons?

A

Tyrosine hydroxylase

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26
Q

reuptake at central noradrenergic neurons is carried out via what transporter? what is the result?

A

NE transporter (NET)
terminates the action of NE in the synapse

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27
Q

Free NE in the presynaptic terminal can be degraded by?

A

Monoamine oxidase (MAO) and Catechol-o-methyltransferase (COMT)

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28
Q

what are the major subtypes of Central Adrenergic Receptors?

A

a1, a2, B1, and B2-adrenoreceptors

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29
Q

NE transporter is the main reuptake transporter for what 2 NTs?

A

serotonin and dopamine

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30
Q

Sympathomimetic (stimulating) effects of cocaine are related to inhibition of what?

A

NE transporter

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31
Q

The NE transporter is the target for what drug class?

A

tricyclic antidepressants

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32
Q

what are the functions of dopamine?

A

motor control, behavior, endocrine responses

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33
Q

Dopaminergic pathways are divided into 3 categories:

A

-Long
-Intermediate (arcuate nucleus to pituitary): DA is a negative
regulator of prolactin. D2 antagonists increase prolactin
-Short (retina and olfactory bulb)

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34
Q

Name the Two Midbrain Nuclei with Long
Axon Dopaminergic Pathways

A

Substantia nigra and Ventral tegmental area (VTA)

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35
Q

Information to know about the Substantia nigra:

A

-Dopamine containing neurons project to the striatum
-This pathway degenerates in Parkinson’s disease
-Led to discovery of therapeutic effects of L-dopa in Parkinson’s
disease
-Side effects of antipsychotic drugs mimic symptoms of
Parkinson’s disease

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36
Q

Information to know about the Ventral tegmental area (VTA):

A

-Project to the limbic structures and cerebral cortex
-mesolimbic and mesocortical pathways
-Doesn’t degenerate in Parkinson’s disease
- A major limbic structure, the nucleus accumbens, is the reward
center in the brain
-Nucleus accumbens plays an important role as a target for drugs
of abuse (amphetamine and cocaine)

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37
Q

what is the rate limiting step of central dopaminergic neurons?

A

Tyrosine hydroxylase

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38
Q

reuptake at central dopaminergic neurons is performed by? what is the result?

A

dopamine transporter (DAT) to terminate the action of DA in the synapse

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39
Q

Free intracellular DA can be degraded by?

A

Monoamine oxidase (MAO) and Catechol-o-methyltransferase (COMT)

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40
Q

what are the two main metabolites of dopamine?

A

homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC).

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41
Q

T/F all dopamine receptors are G coupled

A

True

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42
Q

what are the five subtypes of dopamine receptors?

A

D1-D5

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43
Q

what does the D1 dopamine receptor subtype do?
which subtype(s) is/are similar to D1?

A

increase adenylate cyclase through coupling to Gs
D5

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44
Q

what does the D2 dopamine receptor subtype do?
which subtype(s) is/are similar to D2?

A

decrease adenylate cyclase through coupling to Gi
D3 and D4

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45
Q

what is the main mechanism for extracellular clearance of DA?

A

dopamine transporters

46
Q

what does cocaine target?

A

dopamine transporters

47
Q

what is another name for serotonin?

A

5-Hydroxytryptamine or 5-HT

48
Q

why is serotonin so scarce in the brain?

A

it cannot cross the BBB and thus neurons must synthesize it

49
Q

what various things does serotonin control?

A

Hallucinations, behavioral changes, sleep, wakefulness,
mood, feeding behavior, control of sensory transmission
(startle, avoidance, nociception), regulation of temperature,
blood pressure, sexual function

50
Q

Compare the synthesis and metabolism of dopamine vs serotonin:

A

dopamine process: Tyrosine converts to L-DOPA via tyrosine hydroxylase which converts to dopamine via AADC which can be metabolized by MAO or COMT into HVA
serotonin process: Tryptophan converts to 5-HTP via tryptophan hydroxylase which converts to serotonin via AADC which can be metabolized by MAO or COMT into 5-HIAA

51
Q

Serotoninergic pathways:
location?
function?
similar to?

A

Nine nuclei clustered in the midline or raphe regions of the pons and upper brain stem
sends ascending projections to the forebrain especially limbic structures and cerebral cortex
similar to NE

52
Q

what are the two enzymes involved in enzymatic synthesis of serotonin?

A

tryptophan hydroxylase and aromatic amino acid decarboxylase (AADC)

53
Q

how is serotonin reuptaken by the neuron?
what does it terminate?

A

SERT
the action of 5-HT in the synapse

54
Q

Free 5-HT can be degraded by? It can also by oxidized into?

A

Monoamine oxidase (MAO)
5-hydroxyindoleacetic acid (5-HIAA)

55
Q

what are the 7 subtypes of serotonin receptors?

A

5HT1-5HT7

56
Q

which serotonin receptor subtypes are G coupled?

A

all except 5HT3

57
Q

what do serotonin autoreceptors do?

A

decrease vascular release of 5-HT and decrease 5-HT synthesis

58
Q

In vivo, 5-HT agonists cause what side effects that are comparable to chemotherapy drugs?

A

nausea and vomiting

59
Q

which serotonin receptor is targeted by antiemetic compounds? (what’s an example of an antiemetic compound?

A

5-HT3
Ondansetron: selective 5-HT3 antagonist

60
Q

Lysergic acid diethlamide (LSD), psilocycbin, psilocin are partial agonists at which serotonin receptor?

A

5-HT2 receptors

61
Q

what are the three main Amino Acid transmitters?

A

Glutamate
GABA (y-aminobutyric acid)
Glycine

62
Q

Which amino acid transmitter is the major excitatory neurotransmitter in the brain?

A

glutamate

63
Q

which amino acid transmitters are major inhibitory neurotransmitters in the brain and spinal cord, respectively?

A

GABA (y-aminobutyric acid) and Glycine

64
Q

what synthesizes glutamate?

A

glutamine

65
Q

what is glutamate decarboxylated into? what metabolizes it?

A

GABA by glutamic acid decarboxylase (GAD)

66
Q

what kind of receptors are Ionotropic glutamate receptors?
what NT does it utilize?

A

ligand-gated ion channels
glutamate

67
Q

what kind of receptors are Metabotropic receptors mGluR 1-8?
what NT does it utilize?

A

G-protein coupled receptors
glutamate

68
Q

what are the names of the two Ionotropic Glutamate Receptor Families?

A

NMDA (N-methyl-D-aspartate) and non-NMDA

69
Q

what do NMDA receptors use as a co-agonist?

A

glycine

70
Q

non-NMDA receptors are subdivided into what two receptor types?

A

AMPA receptors and Kainate receptors

71
Q

how many transmembrane domains do glutamate transports have and what is their primary role?

A

12
clear glutamate from the synapse

72
Q

Excitatory neurons contain an electron dense _________ that
is enriched with receptors plus proteins that anchor and cluster receptors for
optimal signal transduction.

A

postsynaptic density (PSD)

73
Q

what are the two types of GABAergic neurons?

A

interneurons and projection neurons

74
Q

what is the enzymatic synthesizing process to produce GABA?

A

glutamine is metabolized by glutaminase into L-glutamic acid which undergoes a-decarboxylation by glutamic acid decarboxylase (GAD) into GABA

75
Q

GABA is reuptaken by what transporter? what is it’s main role?

A

GAT, terminates signal in the synaptic cleft

76
Q

what metabolizes GABA? where is the enzyme found?

A

GABA transaminase
pre and postsynaptic neurons and appears to be
localized in mitochondria

77
Q

GABA A and GABA C are what type of receptors?

A

ligand gated ion channels

78
Q

GABA B are what type of receptor?
what’s an example drug? what does it treat?

A

G-protein coupled receptor negatively coupled to adenylyl cyclase
Baclofen: treat spasticity and muscle/motor disorders – spasm, pain,
and stiffness.

79
Q

what is the resulting effect when GABA binds to GABA A receptors?

A

channel opens allowing Cl- ions to flow down their concentration gradient causing hyperpolarization of postsynaptic neuronal membrane

80
Q

GABA transporters have how many transmembrane domains? what ion are they dependent upon to activate?

A

12
Na2+

81
Q

Inhibitory Glycine Receptors are typically what kind of channel?

A

postsynaptic ligand-gated chloride channel

82
Q

what is a is a competitive glycine antagonist and is considered a powerful lethal convulsant

A

Strychnine

83
Q

where are neuroactive peptides processed? where are they transported to afterwards?

A

the endoplasmic reticulum
the axon terminal

84
Q

neuroactive peptides are degraded by what enzyme?

A

peptidase

85
Q

neuroactive peptides aid in the signaling for what responses?

A

emotion, pain, and stress

86
Q

opioid receptors are activated by the products of 3 endogenous opioid peptide genes which are?

A

Proenkephalin
Prodynorphin
Proopiomelanocortin

87
Q

what are the three opioid receptor subtypes?
what kind of receptors are they?

A

Mu, Delta, and Kappa
All G-protein coupled to inhibition of adenylate cyclase

88
Q

why do opioid receptor agonists increase the risk of respiratory depression?

A

Opioid-induced changes in CO2 sensing in the medulla

89
Q

what are the names of the 4 sections of the brain responsible for feelings of pain? (PAINT)

A

periaqueductal gray, anterior cingulate complex, insula, and thalamus

90
Q

what section of the brain is responsible for your reactivity to pain?

A

the amygdala

91
Q

which two sections of the brain are associated with reward?

A

nucleus accumbens and ventral tegmental area

92
Q

which section of the brain controls breathing?

A

brain stem

93
Q

where in the body can opioid receptors be found?

A

spinal cord, peripheral sensory and autonomic nerves and widely distributed in brain

94
Q

Is histamine excitatory or relaxing?

A

excitatory

95
Q

where is histamine synthesized? where are the neurons it is mainly confined to?

A

the brain
the hypothalamus

96
Q

how is histamine release regulated?

A

released in a circadian rhythm – sleep/wake cycle signaling

97
Q

T/F histamine is required for wakefulness

A

true

98
Q

T/F histamine is reuptaken by HAT

A

False, it has no active reuptake

99
Q

which histamine receptor subtypes are G coupled?

A

H1-H4

100
Q

which histamine receptor subtypes are widely expressed in the brain?

A

H1, H2, H3

101
Q

what classification of receptor is H3?

A

an inhibitory auto/hetero-receptor

102
Q

H1 antagonists that cross the BBB cause what effect?

A

strong sedation

103
Q

why do 2nd generation histamine antagonists not cause strong sedation?

A

have low BBB penetration and thus have fewer CNS effects

104
Q

H2 antagonists such as cimetidine and ranitidine are used for?
do they have strong or weak penetration of the BBB?

A

gastric ulcers
weak penetration

105
Q

the purinergic system has two different receptors called?

A

Adenosine (P1 receptors) and P2 receptors

106
Q

what are the 4 different adenosine receptors? what type of receptor are they considered to be?

A

A1, A2a, A2b, and A3
G protein coupled receptors

107
Q

what are some examples of non-selective adenosine receptor antagonists?

A

xanthine, theophylline, caffeine

108
Q

what is a common beverage source that contains adenosine receptor antagonists?

A

energy drinks

109
Q

what are the two families of P2 receptors and their type?

A

P2X (ligand-gated ion channels) and P2Y receptors (G protein coupled)

110
Q

what are the 4 natural ligands associated with P2 purinergic receptors?

A

ATP, ADP, UTP, UDP

111
Q

what role do endocannabinoids play in regards to synapses?

A

increased activity of endocannabinoids increases Ca2+ concentration to stimulate NT release

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