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Neurobiology (3350) > Lecture 17 - Mental Health & monoamines > Flashcards

Lecture 17 - Mental Health & monoamines Flashcards

1
Q

What are the four diffuse modulatory systems?

A
  1. Noradrenergic Locus Coeruleus
  2. Serotonergic Raphe Nuclei
  3. Dopaminergic Substantia Nigra & Ventral tegmental Area
  4. Cholinergic Basal Forebrain and Brain Stem Complexes
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2
Q

What are the common principles found in each diffused modulatory system?

A
  • Small set of neurons at core
  • Arise from brain stem
  • One neuron influences many others
  • Synapses release transmitter molecules into extracellular fluid and influence surrounding neurons
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3
Q

What is the Noradrenergic – Locus Coeruleus system involved in?

A
  • the regulation of attention
  • arousal
  • sleep-wake cycles,
  • learning and memory,
  • anxiety and pain,
  • mood
  • brain metabolism
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4
Q

When does the Noradrenergic system fire most rapidly?

A

Fire most rapidly during wakefulness in response to new stimuli.

  • Silenced when asleep
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5
Q

Norepinephrine can make neurons of the cerebral cortex more …

A

responsive to salient sensory stimuli

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6
Q

What does the Locus Coeruleus increase?

A

increases

  • brain responsiveness,
  • speeding information processing by the point-to-point sensory
  • motor systems and making them more efficient
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7
Q

What happens if the norepinephrine levels are impaired, or the Locus Coeruleus is impaired?

A

Problems with focus

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8
Q

Which system does the serotonergic system follow?

A

Raphe Nuclei

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9
Q

Where is the serotonergic system found?

A

Clustered along the midline of the brain stem and project extensively to all levels of the CNS

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10
Q

When does the serotonergic system fire most rapidly?

A

Fire most rapidly during wakefulness

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11
Q

The Raphe Nuclei is most similar with which other diffused modulatory system? What are similarities between both?

A
  • Locus Coeruleus
  • Both are part of the reticular activating system (RAS)
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12
Q

What is the reticular activating system?

A

a set of connected nuclei responsible for regulating wakefulness and sleep-wake transitions.

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13
Q

What is the Raphe Nuclei involved in?

A
  • mood modulation (affective disorders, depression)
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14
Q

What happens when there are elevated levels of amino acids in the raphe nuclei?

A

Elevated amino acids in the blood after high protein diet competes and suppress tryptophan transport across the blood-brain barrier.

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15
Q

What happens to the raphe nuclei when a high carbohydrate diets is consummed?

A

Conversely, high carbohydrate diets increase brain tryptophan and serotonin levels and elevated mood (reduced anxiety)

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16
Q

Where is the dopaminergic system found in the brain?

A

Substantia Nigra & Ventral tegmental Area

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17
Q

What are the functions of the dopaminergic system?

A
  • metabolic precursor for norepinephrine
  • a functional neurotransmitter
18
Q

Where is the substantia nigra and ventral tegmental area found?

A
  • the midbrain
  • project to the striatum (caudate nucleus and putamin), limbic and frontal cortical regions
19
Q

How is dopamine involved with the Substantia Nigra & Ventral tegmental Area?

A

Used for the initiation of

  • motor control
  • voluntary movement
20
Q

Which drug causes drug-induced parkisonism?

A

Antipsychotic drug Reserpine, a blocker for VMAT (vesicular monoamine transporter, e.g. serotonin, dopamine, NE)

21
Q

Which drug restores the brain dopaminergic and reverse the side effects of the drug that induces parkisonism?

A

Peripheral injection of L-Dopa can restore the brain dopamine and reverse this side effect of reserpine (no effect on the NE, hence it is not mediated via NE!).

22
Q

Where is the cholinergic diffuse modulatory systems found?

A

In the basal forebrain and brain stem

23
Q

What are the first cells to die during the course of alzheimer’s disease? How is alzheimer’s characterized?

A
  • cholinergic neurons
  • characterized by a progressive and profound loss of cognitive functions.
24
Q

T or F. Targeting cholinergic system is not effective in treating AD.

A

True

25
Q

What happens when a stimulant, like cocaine or amphetamine, is taken?

A

Feeling of increased alertness and self-confidence, a sense of exhilaration and euphoria, and a decreased appetite (sympathomimetic)

26
Q

How does cocaine work with diffuse modulatory systems?

A

Cocaine targets DA reuptake more selectively (making you more happy)

27
Q

How does amphetamine work with diffuse modulatory systems?

A

amphetamine blocks NE and DA reuptake and stimulates the release of DA

28
Q

How do psychotropic drugs function with diffuse modulatory systems?

A
  • prolong and intensify the effects of released DA or NE.
  • Enhanced transmission in the mesocorticolimbic dopamine system during drug use would lead to pleasure (drug)-seeking behavior, i.e. addiction.
  • Amphetamine and cocaine block NE and DA reuptake, thereby alowing NE and DA to remain ni the synaptic cleft longer.
29
Q

Research evidence points to what in schizophrenia?

A

Hypofunction of glutamate receptors (NMDR) lead to early cognitive deficits and alters dopaminergic homeostasis (i.e., hyperdopamine in the striatum and cortex) leading to SZ symptoms.

30
Q

How do treatments for people with schizophrenia work?

A

targeting dopamine (with D2R antogonists) to remedy the “positive” symptoms of psychosis

  • not “negative” upstream symptoms present before diagnosis, like cognitive impairments, social isolation, anxiety/depression and impaired pre-pulse inhibition (PPI) of the acoustic startle
    response
31
Q

What are some structural defects of people with schizophrenia?

A
  • increased ventricle to-brain-size ratio
  • defects in the myelin sheaths surrounding axons in their cerebral cortex
  • abnormal clusters of neurons
  • alterations in chemical synaptic transmission mediated by dopamine and glutamate.
32
Q

What is the dopamine hypothesis?

A

Psychotic episodes in schizophrenia triggered by activation of dopamine receptors

32
Q

What are differences in ventricle size for schizophrenic patients?

A

enlarged lateral ventricles in the schizophrenic sibling, indicating a loss of brain tissue

33
Q

How do Monoamine oxidase inhibitors work?

A

enhance the actions of NE and 5-HT by preventing their enzymatic destruction.

34
Q

How do tricyclics work?

A

enhance NE and 5-HT action by blocking uptake

35
Q

How do SSRIs work?

A

Same as tricyclics but are selective for serotonin

36
Q

What is the glutamate hypothesis?

A

schizoprenia reflects diminished activation of NMDA receptors in the brain causing low amounts of glutamate in the brain.

37
Q

What is glutamate?

A

Fast excitatory neurotransmitter in the brain, two important receptor subtypes, AMPA and NMDA

38
Q

What are the treatments for schizophrenia?

A
  • drug therapy combined with psychosocial support
  • neuroleptics (chlorpromazine and haloperidol - act at D2 receptors) - they reduce positive symptoms but have many side effects (akathisia, dystonia, tardive dyskinesia etc.)
  • NMDA receptor agonists (like clozapine)
39
Q

What occurs when mice is genetically altered to express fewer NMDA receptors?

A

mice tend to avoid social contact with one another

Neurobiology (3350) (8 decks)

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