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Physiology 2: neuro > Monoamines > Flashcards

Monoamines Flashcards

1
Q

Neuromodulation

A

The physiological (Links to an external site.) process by which a given neuron (Links to an external site.) uses one or more chemicals to regulate diverse populations of neurons.

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2
Q

Neuromodulators

A

Neurotransmitters that diffuse through neural tissue to affect slow-acting receptors of many neurons.

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3
Q

Locus Coeruleus

A

It is a nucleus (Links to an external site.) (site of brain synthesis of noradrenalin) in the pons (Links to an external site.) of the brainstem (Links to an external site.) involved with physiological (Links to an external site.) responses to stress (Links to an external site.) and panic (Links to an external site.).

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4
Q

Raphe Nuclei

A

A collection of nuclei of neurons in the brainstem that produce serotonin.

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5
Q

Basal Forebrain Complex

A

Located in the forebrain to the front of and below the striatum. They include the nucleus accumbens, nucleus basalis, diagonal band of Broca, substantia innominata, and the medial septal nucleus. Rich in cholinergic neurons

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6
Q

Hallucinogens

A

Compounds/drugs which produce hallucinations (e.g. LSD, Psilocybe)

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7
Q

Stimulants

A

a drug that produces a temporary increase in psychomotor activity and usually induce feelings of euphoria, alertness and self-confidence (e.g. cocaine, amphetamine)

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8
Q

4 main modulatory systems

A

– Noradrenergic Locus Coeruleus
– Serotonergic Raphe Nuclei
– Dopaminergic Substantia Nigra and Ventral tegmental Area
– Cholinergic Basal Forebrain and Brain Stem Complexes

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9
Q

4 system principles for the modulatory system

A

– Small set of neurons at the core
– Arise from brain stem
– One neuron influences many others
– Synapses release transmitter molecules into the extracellular fluid

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10
Q

5-HT1

A

Inhibits Adenylyl cyclase

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11
Q

5-HT2

A

Stimulates phospholipase C

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12
Q

Dopamine D1

A

Stimulates Adenylyl cyclase

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13
Q

Dopamine D2

A

Inhibits Adenylyl cyclase

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14
Q

Noradrenaline beta

A

Stimulates Adenylyl cyclase

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15
Q

Noradrenaline alpha 1

A

Stimulates phospholipase C

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16
Q

Noradrenaline alpha 2

A

Inhibits Adenylyl cyclase

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17
Q

Behavioural effects of modulatory systems

A

Mood, memory, reward, movement, motivation

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18
Q

Noradrenaline causes

A
  • Arousal
  • Wakefullness
  • Exploration and mood
  • (low NA in depressed)
  • Blood pressure
  • Addiction/gambling
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19
Q

Hypothalamus

A

Hormones, sleep, body temperature, endocrine and autonomic controller)

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20
Q

Locus coeules

A

known as ‘blue spot’ because of pigmentation. NA in this region makes the brain more responsive, increases information processing

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21
Q

Regulation of NA

A

Post-synaptic
– Carry on the message
Pre-synaptic (autoreceptors)
– Usually inhibitory
– Negative feedback mechanism
• Reserpine-depletes NA stores by inhibiting vesicular uptake
• Amphetamine (indirect sympathomimetic)-enters vesicles displacing NA into cytoplasm, increase NA leakage out of neuron

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22
Q

Noradrenaline

A
  • Reserpine-depletes NA stores by inhibiting vesicular uptake
  • Amphetamine (indirect sympathomimetic)-enters vesicles displacing NA into cytoplasm, increa NA leakage out of neuron
  • Cocaine-blocks NA re-uptake
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23
Q

Amphetamine

A

Increase alertness and exploratory behaviour

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24
Q

Where is there a lot of Noradrenaline

A

High density in brainstem, hypothalamus & medial temporal lobe

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25
Functions of Noradrenaline
* Arousal, wakefullness, exploration and mood (low NA in depressed patients) * Blood pressure regulation, (antihypertensive e.g. clonidine 2) * (Addiction/gambling)
26
Functions of Noradrenaline
* Arousal, wakefulness, exploration and mood (low NA in depressed patients) * Blood pressure regulation, (antihypertensive e.g. clonidine 2) * (Addiction/gambling)
27
NA and cell bodies
cell bodies in brain stem largest group in locus coeruleus (LC) in the pons. LC neurons silent during sleep and activity increases with arousal – especially in response to unfamiliar and threatening stimuli. Low NA – low arousal – found in depressed patients
28
What is NA main cell body?
Locus Coeruleus
29
NAergic pathways & Daergic and the limbic system
Play role in the reward system and are implicated in drug dependence
30
NAergic synapses
Found in medulla form part of the baroreceptor reflex pathway – regulation of blood pressure
31
Amphetamine-like drugs
Release catecholamines and increase wakefulness, alertness and exploratory behaviour.
32
Dopamine is involved in what?
Movement Reward Inhibition of prolactin release Memory consolidation
33
Diseases associated with dopamine
``` Parkinson’s Disease Schizophrenia Addiction Emesis ADHD ```
34
Tuberohyphyseal pathway
Prolactin secretion
35
VTA – mesocorticolimbic dopamine system
DA projection from midbrain. Important in addiction and schizophrenia / psychoses
36
Substantia nigra
Projects to the striatum important for control / initiation of voluntary movement
37
Main dopamine pathways
* Substantia nigra to basal ganglia (Parkinson’s disease) | * Midbrain to limbic cortex (schizophrenia)
38
Other functions of dopamine
Movement, addiction, stereotypy, hormone release, vomiting
39
5-HT3 (serotonin)
Ion channel PNS neuronal excitat
40
Serotonin
5- HT
41
What type of receptors is serotonin receptors?
14 subtypes | All G-protein coupled except 5-HT3
42
5-HT1
Limbic system mood, migraine
43
5-HT2 (5-HT2A)
Excitatory, hallucinogenic, limbic system & cortex
44
5-HT3
Excitatory medulla vomiting
45
5-HT4
Presynaptic facilitation (ACh) Cognitive enhancement
46
5-HT6 and 5-HT7
Novel targets, cognition, sleep
47
Main functions of serotonin
* Mood * Psychosis * Sleep/wake (5-HT linked to sleep, 5-HT2 antagonists inhibit REM sleep) * Feeding behaviour * Pain, migraine (5-HT inhibits pain pathway, synergistic with opioids) * Vomiting,
48
Disorders related to serotonin
(anxiety/depression) (5HT antagonism antipsychotic) (5HT2A antagonist increase appetite, weight gain; antidepressants decrease appetite
49
Dopamine
DAT (on dopamine neurons)
50
5-HT
SERT (on 5-HT neurons)
51
NA
NET (on noradrenaline neurons)
52
Glutamate
EAAT1 (mostly on astrocytes)
53
Dopamine
vMAT2 (into vesicles)
54
Monoamine transporters
12 TMDs Both ends intracellular Pump monamines in neuron DA, NA, 5HT transporters
55
Acetylcholine is involved in part 1
* Memory, learning * Motor control (striatum) * Reward * Arousal * Alzheimer’s * Pain
56
Acetylcholine is involved in part 2
* Addiction * Epilepsy (nAChR genes) * Schizophrenia * ADHD * depression * anxiety,
57
Functions with acetylcholine
* Arousal * Epilepsy (mutations of nAChR genes) * Learning and memory (KO mice) * Motor control (M receptors inhibit DA), pain, addiction * Involved in schizophrenia, ADHD, depression, anxiety, Alzheimers
58
Histamine
– H1 (arousal) and H3 (presynaptic / constitutively active) – Functions: sleep / wake, vomiting – Purines – Adenosine (A1, A2A/2B) and ATP (P2X) – Functions: sleep, pain, neuroprotection, addiction, seizures, ischaemia, anticonvulsant – Neuropeptides – Opioid peptides (kappa, delta. mu) – Tachykinins (Substance P, neurokinin A & neurokinin B) • NK1 (Substance P), NK2 (neurokinin A), NK3 (neurokinin B)
59
Proopioimelanocortin (Beta-endorphin)
MOP and DOP
60
Proenkephalin (Enkephalins)
DOP
61
Prodynorphin | Dynorphins
KOP
62
Pronociceptin | Nociceptin/OFQ
NOP
63
Melatonin
- MT1, MT2 receptors | - involved in sleep regulation, circadian rhythmicity, agonists for jet lag and insomnia
64
Lipid mediators
- Products of conversion of eicosanoids to endocanabinoids - act on CB1 (inhibit GABA, glutamate release) - involved in vomiting (CB1 agonist block it, MS, pain, anxiety, weight loss/rimonabant CB1 antogonist)
65
Drugs interacting with the diffuse system | Psychostimulants: Amphetamine
* Amphetamine-like drugs (methylphenidate & MDMA) * Release cytosolic monoamines (DA) * Prolonged use neurotoxic * Degeneration of amine-containing nerve terminals, cell death
66
Pharmacological effects of Psychostimulants: Amphetamine
* increase alertness and locomotor stimulation (increase aggression) * Euphoria/excitement * Stereotyped behaviour * Anorexia * decrease physical and mental fatigue (improves monotonous tasks) * Peripheral sympathomimetic actions (increase blood pressure & decrease gastric motility) * Confidence improves/lack of tiredness
67
Therapeutic uses of Psychostimulants like Amphetamine
ADHD (methylphenidate), appetite suppressants, narcolepsy
68
Cocaine
Blocks catecholamine reuptake | • (increases DA, stimulant effect)
69
Cocaine Pharmacological effects
* Euphoria * Locomotor stimulation * Fewer stereotyped behaviours than amphetamine * Heightened pleasure * Lower tendency for delusions, hallucinations and paranoia
70
Cocaine Pharmacokinetics
* HCl salt, inhaled and i.v. administration * Nasal inhalation less intense, leads to necrosis of nasal mucosa * Freebase form (‘crack’), smoked, as intense as i.v route
71
MDMA
Inhibits monoamine transporters (mainly 5-HT) Large increase 5-HT (followed by depletion) Increases 5-HT linked to psychotomimetic effects Increases DA linked to euphoria (followed by rebound dysphoria)
72
LSD, Psylocybin
• Hallucinogenic effect by acting on 5HT2 receptors
73
Psychostimulants
* Also increase 5HT and NA | * Cocaine block DAT, NET, SERT

Physiology 2: neuro (19 decks)

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