CNS Neurotransmitters Flashcards

1
Q

What are the monoamine neurotransmitters?

A
  • Norepinepherine (NE)
  • Serotonin (5-HT)
  • Acetylcholine (ACh)
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2
Q

What are the amino acid neurotransmitters?

A
  • Glutamate (Excitatory)
  • GABA (Inhibitory)
  • Glycine (Inhibitory)
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3
Q

What are the neuropeptide neurotransmitters?

A
  • Endorphin
  • Angiotensin
  • Substance P
  • Many others
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4
Q

What type of staining showed the nervous system was a collection of individual neurons?

A

Golgi staining

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5
Q

Describe the two types of transmission speeds and the charactestics of each.

A
  • Fast
    • Rapid, point-to-point, transient (doesn’t last long)
    • Involve transmitter-gated ion channels (ionotropic)
    • Typicall triggered by a single depolarizatoin
  • Slow
    • Slow, diffuse, lasting
    • Involve G-protein coupled receptors (metabotropic)
    • Typically triggered by prolonged or repetative depolarization
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6
Q

What functional groups do monoamine neurotransmitters consist of? What is the exception to this?

A
  • Amine group connected to an aromatic ring by a two carbon chain
    • ACh is not a monoamine but is clumped together with this group
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7
Q

What enzyme converts glutamate (excitatory) to GABA (inhibitory)?

A

Glutamic acid decarboxylase (GAD)

  • Wherever there is glutamate, there is also GAD
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8
Q

What determines if a neuron is inhibitory or excitatory? What is the exception?

A
  • It’s receptor
    • Gluatamate - Always excitatory
    • GABA - Always inhibitory
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9
Q

What neurotransmitters work together to tightly regulate different neural functions?

A

Glutamate & GABA

  1. Glutamate released into cleft
  2. Binds post-synpatic neurons
  3. Neurons can take up Glutamate and convert to GABA
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10
Q

What receptor is believed to be the source of learning?

A

Glutamate-NMDA receptor

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11
Q

Describe the Glutamate-NMDA recptor firing.

A

NMDA is a slective agonist to glutamata

  1. NMDA, Glutamate, and depolarization from -80mV to -40mV are required to fire
  2. Depolarization frees a Mg<strong>2</strong>+ that blocked channel
  3. Ca2+ influx results (Voltage gated)
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12
Q

What is synaptic plasticity?

A

Regulation of strength of connection between two synapses

  • Seen in Glutamate-NMDA receptor
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13
Q

What is glutamate toxicity?

A

Too much glutamate from:

  • Excessive gluatamate release
  • Poor glutamate reuptake

Excessive Ca2+ intake triggers neuronal injury/death

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14
Q

What can cause glutamate toxicity?

A

Stroke: Anoxia can release toxic amounts of glutamate

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15
Q

What is the mechanism of the GABAA receptor and what drugs act on it?

A

Hyperpolarization via Cl- influx into neuron

Drugs:

  • Benzodiazepines
  • Barbituates
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16
Q

What is the mechanism of the GABAB receptor and what drugs act on it?

A

Hyperpolarization via K+ outflux from neuron

Drugs:

  • GHB
  • Baclofen
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17
Q

What is the disease model for Huntington’s?

A

Destruction of GABAergic neurons in basal ganglia

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18
Q

What is the disease model for Tetanus and Strychnine?

A

Inhibition of presynaptic GABA release (results in shortage of GABA in synaptic cleft)

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19
Q

What is the disease model in Stiff-Person Syndrome?

A

Antibodies destroy GAD and prevent GABA production, causing autoimmune or paraneoplastic syndrome

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20
Q

What drugs can treat excessive glutamate? (Increased glutamate can cause seizures)

A
  • Benzodiazepines (increase GABA efficiency)
  • Valproate (Inhibit enzymes that deactivate GABA)
  • Topiramate (Inhibit GABA re-uptake)
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21
Q

What are the side effects of treating excessive glutamate with GABA?

A
  • Sedation
  • Cognitive slowing
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22
Q

What are the non-therapeutic uses of drugs that increase GABA?

A
  • Anxiolysis, hypnosis, amnesia (occasionally)
  • High addictive potential
  • “Date-rape” drugs
    • GHB (Gamma-hydroxybutrate)
    • Benzodiazepines
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23
Q

What nuclei produce Dopamine?

A
  • Pars compacta (substantia nigra) - largest
  • Ventral tegmental area
  • Hypothalamus
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24
Q

Describe the Nigrostriatal tract.

A
  • Substania nigraStriatum (D2 receptors)
  • Regulates fluid and smooth muscle action
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25
Q

Describe the Mesolimbic tract.

A
  • Ventral tegmental areaN. accumbens (D1 receptors; part of limbic system)
  • Associated with fear & reward responses
26
Q

Describe the mesocortical tract.

A
  • Ventral tegmental areaFrontal lobe
  • Associated with motivation and response
27
Q

Describe the Tubero-infundibular tract.

A
  • Hypothalamus → Pituitary
  • Regulates secretion of hormones, notably prolactin
28
Q

What are the 4 clinically imporant tracts associated with dopamine?

A
  • Nigrostriatal tract
  • Mesolimbic tract
  • Mesocortical tract
  • Tubero-infundibular tract
29
Q

Parkinson’s disease is associated with death of what structures?

A

Pars compacta (within substantia nigra) - Decreased dopamine

30
Q

What are the primary and secondary symptoms related to Parkinson’s disease?

A
  • Primary: Movement-related disorders
    • Shaking, rigidity, slowness, difficulty with gait
    • Lack of DA to reach receptors to gait/initiate movements
  • Secondary: Cognitive disorders
    • Dementia, sensory, sleep, emotional lability
31
Q

What illicit drugs block the re-uptake of Dopamine? What is the effect?

A
  • Cocaine and methamphetamine
  • Excessive dopamine can cause paranoia, hallucinations, delusions, disorganized thoughts
  • Results in reward dysfuntion
32
Q

What can be used to treat Parkinsons (decreased dopamine)?

A

L-DOPA (bypasses rate limiting step of converting tyrosine to DOPA by tyrosine hydroxylase)

33
Q

What are the neurotransmitters changes associated with depression and what can be used to treat it?

A
  • Decreased dopamine and serotonin
  • Buproprion/Methylphenidate (prevent DA re-uptake)
34
Q

What are the neurotransmitter changes associated with ADHD and what drugs can be used to treat it?

A
  • Decreased dopamine and norepinepherine
  • Bupropion/Methylphenidate (prevent re-upatke of DA)
35
Q

What are the neurotransmitter changes associated with Schizophrenia and what drugs can be used to treat it?

A
  • Increased dopamine
  • Antipsychotics (operate via D2 receptor antagonism)
36
Q

What nucleis produce serotonin (5-HT)?

A

Raphe nucleus (pons/midbrain)

37
Q

What tracts are associated with serotonin (5-HT)?

A

Many; extensive projections throughout brain including:

  • Cortex
  • Cerebellum
  • Hypothalamus
  • Spinal column
  • PNS
38
Q

What disorders are associated with decreased serotonin?

A
  • Major depressive disorder
  • Anxiety disorders
  • Nausea (increased, not decreased)
39
Q

What are the drugs used to treat major depressive disorder?

A
  • SSRIs
  • TCA
  • MAO inhibitors
40
Q

What are the drugs used to treat anxiety disorders?

A
  • Benzodiazepines (DOC)
  • SSRIs
  • TCA
  • MAO inhibitors
41
Q

What are the drugs used to treat nausea?

A

Ondansntron (5-HT3 receptor antagonist)

42
Q

What is the rate limiting step in serotonin production?

A

Tryptophan → 5-HTP

TPH (Tryptophan hydroxylase)

43
Q

What is serotonin syndrome and what are the symptoms?

A
  • Excessive serotonin
  • Cognitive symptoms: Headache delerium
  • Autonomic symptoms: Hyperthermia, hypertension
  • Somatic symptoms: Tremor, hyperreflexia, clonus
44
Q

What drugs of abuse can causes serotonin disorders?

A
  • LSD
  • MDMA
45
Q

What food and beverages can cause serotonin disorders?

A
  • Cheese (tyramine)
  • EtOH
46
Q

What nuclei produce norepinepherine? What is it responsible for?

A
  • Locus ceruleus (pons)
  • Fight or flight response
  • Smooth muscle contraction or relaxation, heart muscle contraction, glycogenolysis
47
Q

What tracts are associated with norepinepherine?

A

Broad projectsion throughout cortex (frontal), limbic, spinal

48
Q

What neurotransmitter changes are associated with Parkinsons?

A
  • Decreased NE (locus ceruleus destruction) secondarily due to decreased DA (substania nigra destruction) - Must have dopamine to make NE
  • Increased 5-HT
  • Increased ACh
49
Q

Panic attacks are associated with increased levels of what neurotransmitter?

A

Increased norepinepherine (due to re-uptake deficiency)

50
Q

What drugs can be used to treat norepinepherine disorders?

A
  • Antidepressants (increase NE availability)
  • Selective NE/DA re-uptake inhibitor (Bupropion)
  • SSNRIs (Vanlafaxine, duloxetine)
51
Q

What nucleus produces ACh?

A
  • Nucleus Basalis of Mynert (inferior to anterior commissure)
  • Pedunculopontine nucleus (brainstem, caudal to substantia nigra)
52
Q

What tracts are associated with ACh?

A

Pedunculopontine - Projects to:

  1. Thalamus, basal ganglia
  2. Brainstem, deep cerebellar nuclei

Nucleus Basalis of Mynert - Projects to:

  1. Cortex, associated with memory, learning, defecits with Alzheimer’s

Parasympathetic nervous system

  1. Heavily involved with limbic system and homeostasis
53
Q

Alzheimer’s disease is associated with what neurotransmitter changes?

A
  • Decreased ACh (degeneration of NBM)
  • Loss of nACh receptors in hippocampus
54
Q

The hippocampus in normal, healthy adults is rich in what?

A

Nicotnic ACh receptors

Linked to cognition

55
Q

Schizophrenia shows reduction of what type of receptors?

A

Nicotinic ACh receptors in hippocampus and frontal cortex

Cigarette smoking is commonly believed to be form of self-medicatoin

56
Q

What is required for nictonic ACh receptors to fire?

A
  • ACh
  • Nicotine
57
Q

What is required for muscarinic ACh receptors to fire?

A
  • ACh
  • Muscarine
58
Q

What can cause ACh toxicity and what is used to treat it?

A

Organophosphates/Sarin gas

Atropine (anti-muscarinic)

59
Q

What are the symptoms of ACh toxicity at nicotinic receptors?

A

SLUDGE

  • Salivation
  • Lacrimation
  • Urination
  • Defacation
  • GI upset
  • Emesis
60
Q

What are the symptoms of too little ACh (anticholinergic toxicity) at muscarinic receptors?

A
  • Increased body temperature and sweating (hot as a hare)
  • Loss of accomidation (blind as a bat)
  • Decreased secretions (dry as a bone)
  • Disorientation from CNS manifestations (mad as a hatter)
61
Q

What drugs can cause anticholinergic toxicity (too little ACh)?

A
  • Anti-nausea medications
  • Antidepressants
  • Antipsychotics
  • Anti-histaminics