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Neurophysiology > Neurotransmitter systems III: Monoamines > Flashcards

Neurotransmitter systems III: Monoamines Flashcards

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1
Q

What are the central nervous systems which controls behaviour?

A

Autonomic Nervous System

Hypothalamic-Pituitary Neurohormones

Diffuse Monoamine Modulatory System

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2
Q

What are the Diffuse monoamine modulatory systems?

A

4 monoamine modulatory systems:

  • Noradrenaline: Noradrenergic Locus Coeruleus
  • Serotonin (5-HT): Serotonergic Raphe Nuclei
  • Dopamine: Dopaminergic Substantia Nigra and Ventral Tegmental Area
  • Acetylcholine: Cholinergic Basal Forebrain and Brain Stem Complexes
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3
Q

What do the 4 diffuse modulatory systems have in common?

A

Ø Released from neurones which arise from brain stem
Ø Neurones project from central core where cell bodies are located to many different regions of the brain where the neurotransmitter gets released
Ø One neurone influences many others
Ø Synapses release transmitter molecules into extracellular fluid

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4
Q

What type of receptors are monoamine receptors?

A

G-protein coupled receptors

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5
Q

Describe the Noradrenergic modulatory pathway.

A

noradrenergic neurones project from central core called Locus Coerulus to different brain regions (e.g. cortex, amygdala, hypothalamus, cerebellum, spinal cord)

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6
Q

Describe the Action of noradrenaline at synaptic bouton.

A

1) Noradrenaline gets into synaptic vesicles
2) Noradrenaline released upon stimulation by action potential
3) Noradrenaline binds to post-synaptic noradrenergic receptors (G-coupled) to carry on the message
4) Noradrenaline also activates pre-synaptic auto-receptors (a2 receptors) which act via a negative feedback mechanism and inhibit the release of noradrenaline

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7
Q

What are the Effects of increased noradrenaline?

A
  • Cardiovascular effects (tachycardia, high blood pressure)
  • Addictive-like behaviour (gambling)
  • Hyperarousal
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8
Q

What are the Effects of decreased noradrenaline?

A
  • Depression

- Parkinson’s disease

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9
Q

Describe process of Noradrenaline Regulation: Reuptake mechanism.

A

noradrenaline transporters on pre-synaptic membrane reuptake excess noradrenaline from synapse

once inside the synapse, noradrenaline is metabolised and broken down by monoamine oxidase (MAO), terminating its action

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10
Q

Describe the structure of Noradrenaline receptors.

A

G-protein coupled receptors:

  • Alpha 1 (Gq)
  • Alpha 2 (Gi)- autoreceptors
  • Beta (Gs)
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11
Q

What are the Drugs that increase noradrenaline levels?

A

· Reserpine: depletes noradrenaline stores by inhibiting vesicular uptake

· Amphetamine (indirect sympathomimetic): enters vesicles displacing NA into cytoplasm, increasing NA leakage out of neurone into synapse

· Cocaine: blocks NA reuptake

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12
Q

Describe the Action of drugs in depression treatment.

A

Drugs to increase noradrenaline:

  • block monoamine oxidase (MOA)
  • block noradrenaline transporters
  • block serotonin transporters
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13
Q

What are the Dopaminergic Modulatory Pathways?

A

Nigrostriatal Pathway

Mesolimbic Pathway

Mesocortical Pathway

Tubero-hypophyseal Pathway

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14
Q

Describe the Nigrostriatal pathway.

A

dopaminergic neurones project from substantia nigra (SN), where cell bodies are found, to the striatum where dopamine is released to induce MOVEMENT

*degeneration of these neurones decreasing dopmaine levels in the striatum, causing Parkinson’s disease (suppressed movement)

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15
Q

Describe the Mesolimbic pathway.

A

dopaminergic neurones project from ventral tegmental area (VTA) to amygdala, hippocampus and nuclear accumbens, where dopamine is released to induce REWARD (e.g. food, sex)

  • Abused drugs over-stimulate this pathway, increasing pleasure/reward, leading to addiction
  • Hyperactivity of this system causes psychotic episodes in schizophrenics
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16
Q

Describe the Mesocortical pathway.

A

dopaminergic neurones project from ventral tegmental area (VTA) to the cortex, where dopamine is released

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17
Q

Describe the Tubero-hypophyseal pathway..

A

dopaminergic neurones project from hyopthalamus to the portal capillary system in the median eminence where dopamine is released, acting as a neurohormone by binding to its receptors in the anterior pituitary and inhibiting release of prolactin

*prolactin responsible for mammary gland enlargement and milk production

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18
Q

Dopamine is involved in…

A 
addiction (gambling)
emesis
ADHD
Schizophrenia (hyperactivity of mesolimbic pathway)
Parkinson's disease (lack of dopamine)
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19
Q

Describe the porcess of Synthesis of Catecholamines.

A

1) Tyrosine is converted to DOPA by tyrosine hydroxylase
2) DOPA is converted to dopamine via DOPA decarboxylase
3) Dopamine is then metabolised to noradrenaline via Dopamine-β hydroxylase
4) Noradrenaline can then further be metabolised to adrenaline

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20
Q

What determines whether a neurone is dopaminergic or noradrenergic?

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A

The presence of Dopamine-β hydroxylase in excess makes neurones dopaminergic

Neurones without this enzyme are noradrenergic

21
Q

What are the Effects of increased dopamine?

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A

addiction

psychosis

22
Q

What are the Effects of decreased dopamine?

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A

Parkinson’s disease

23
Q

Describe the process of Dopamine Regulation: Reuptake Mechanism.

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A

dopamine transporters on pre-synaptic membrane reuptake excess dopamine from synapse

once inside the neurone, dopamine is metabolised and broken down by monoamine oxidase b (MOAb), terminating its action

24
Q

Describe the Actions of drugs in Parkinson’s treatment.

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A

Drugs to increase dopamine:

  • block monoamine oxidase b (MOAb)
  • block dopamine reuptake transporters
25
Describe the structure of Dopamine Receptors.
D1-like (Gs coupled) >D1 & D5 D2-like (Gi coupled) >D2, D3, D4
26
Where are dopamine receptors are found?
- Post-synaptic D1 and D2 receptors - Pre-synaptic D2 or D3 auto-receptors · D1 and D2 receptors are found in the striatum, limbic system, thalamus and hypothalamus · D3 receptors are found in the limbic system · D4 receptors are found in the cortex and limbic system
27
Dopamine is associated with...
``` movement addiction stereotypy hormone release vomiting ```
28
Describe the Serotonergic pathway.
serotonergic neurones project from central core called Raphe nucleus to regions such as cerebellum, cortex, striatum, hippocampus, amygdala, thalamus, hypothalamus, spinal cord, where serotonin is released
29
What is the Effect of serotonin?
Different effects in different brain regions: · Binds to receptors in cortex and causes heightened perceptions · Binds to receptors in hypothalamus and reduces appetite · Binds to receptors in amygdala and causes elevated mood Other effects: - sleep/wake cycle - vomiting - psychosis - reducing pain, migraine
30
Describe the Synthesis of Serotonin.
Precursor of serotonin is the amino acid tryptophan: 1) Tryptophan is metabolised by tryptophan hydroxylase to 5-hydroxytryptophan 2) 5-hydroxytryptophan is metabolised by L-Aromatic acid decarboxylase to serotonin (5-HT) 3) 5-HT can be metabolised further by monoamine oxidase to 5-hydroxyindoleacetylaldehyde 4) This metabolite can be further metabolised to 5-HIAA (5-hydroxyindoleacetic acid) by aldehyde dehydrogenase
31
What are the Effects of low serotonin?
depression
32
Describe the process of Serotonin Regulation: Reuptake Mechanism.
Serotonin transporters on pre-synaptic membranes reuptake excess serotonin from the synapse once inside the neurone, the serotonin is metabolised and broken down by monoamine oxidase (MOA), terminating its action
33
Describe the structure of Serotonin receptors.
Post-synaptic and pre-synaptic 5-HT receptors (14 subtypes): | -all G-protein coupled receptors apart from one (5-HT3) which is an ion channel
34
Describe the structure of Monoamine Transporters.
These take the neurotransmitter back up into the pre-synaptic terminal. - 12 transmembrane domains - both ends intracellular - pump monoamines (NA, DA, 5HT) in neurone
35
Describe the Cholinergic Modulatory Pathways.
Septohippocampal Pathway -cholinergic neurones project from the septum to the hippocampus, where acetylcholine is released Nucleus Basalis -cholinergic neurones project from the nucleus basalis to the cortex where acetylcholine is released Striatal Interneurons -small cholinergic neurones called striatal interneurons found within the striatum release acetylcholine. Substantia Nigra -cholinergic neurones project from the substantia nigra to the thalamus, where acetylcholine is released.
36
What are cholinergic neurones involved in?
cognition learning memory
37
What does the degeneration of cholinergic neurones cause?
dementia and Alzheimer's, causing for cognitive symptoms such as memory loss
38
Describe the structure of Acetylcholine receptors.
Muscarinic (G-protein) - M1,3,5 excitatory - M2&4 inhibitory Nicotinic (ligand-gated ion channels)
39
Describe the process of Acetylcholine Regulation.
Acetylcholinesterase breaks down acetylcholine to choline and acetate, terminating its activity Choline then is re-uptaken into pre-synaptic neurone to be recycled
40
Describe the Action of drugs to treat dementia/Alzheimer's.
Drugs increase acetylcholine levels: | -inhibit acetylcholinesterase enzyme
41
Acetylcholine is involved in...
``` arousal epilepsy (mutations of nAChR genes) learning and memory motor control, pain, addiction schizophrenia ADHD depression anxiety Alzheimer's ```
42
Give some Other transmitters/modulator substances.
``` Histamine Purines Neuropeptides Lipid Mediators Melatonin ```
43
What are opioid peptides (neuropeptides) derived from?
a bigger protein e.g. β endorphin is derived from pro-opiomelanocortin (POMC) once the peptide is released from the neurone it acts on receptors
44
How are neuropeptides synthesized?
- Encoded by DNA - Gene modified in rER and Golgi - Proteolytic cleavage in Golgi breaks down big proteins into many different peptides e.g. β endorphin, which are stored in synaptic vesicles for release upon stimulation
45
Which drugs interact with the diffuse system?
Amphetamine (psychostimulant) | Cocaine (central stimulant)
46
What are Amphetamine-like drugs?
methylphenidate & MDMA: - release cytosolic monoamines - prolonged use causes degeneration of nerves and death (neurotoxic) Pharmacological effects: - increased alertness and locomotor stimulation (increased aggression) - stereotyped behaviour - anorexia - less physical and mental fatigue - increased blood pressure - decrease gastric motility - improved confidence/lack of tiredness
47
Give some Therapeutic uses of amphetamine-like drugs.
Therapeutic uses: - ADHD (methylphenidate) - Appetite suppressants - Narcolepsy
48
What is the effect of Cocaine?
blocks catecholamine reuptake, increasing dopamine at synapse Pharmacological effects: - euphoria - locomotor stimulation - fewer stereotyped behaviour than amphetamine - heightened pleasure - lower tendency for delusions, hallucinations and paranoia

Neurophysiology (10 decks)

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