6. Neurotransmitters

June 25, 2015 by Dr. Tangen Leave a Comment

This is your brain on drugs, naturally.

“Just Say No” doesn’t apply to these drugs. Neurotransmitters are built-in drugs. You have to have them to make interconnections between neurons.

If the activity within a neuron is primarily electrical (though battery driven), the connections between neurons are typically chemical. Once a neuron’s depolarization reaches the terminal buttons, calcium channels are activated to release neurotransmitters into the synapse.

Here’s what is included in this lesson:

dopamine & why it’s addictive
nor-epinephrine (noradrenaline)
epinephrine (adrenaline)
Parkinson’s & schizophrenia
adrenaline junkie

Here are some resources for you:

AUDIO

Here are some short audio sound bites about neurotransmitters.

Monoamines

Catecholamines

Dopamine

SLIDES

TERMS

acetylcholine (Ach)
adrenaline
adrenaline junkie
adrenergic receptors
Alzheimer’s disease
amphetamines
anaphylaxis
antidepressants
antipsychotic Drugs
atropine
benzene ring
catecholamines
cocaine
COMT
curare
deadly nightshade
degradation
dopamine
endorphins
epinephrine (adrenaline)
GABA
glutamate
hormone
indolamine
ionotrophic
L-DOPA
LSD
MAO
metabotrophic
monoamines
muscaninic acetylcholine receptors (mAChR)
muscle
myasthenia gravis
neuromodulator
niacin (B3)
nicotinic acetylcholine receptors (AChR)
norepinephrine (noradrenaline)
norepinephrine transporter
phasic release
plasma proteins
platelets
re-uptake
reward-anticipation
schizophrenia
serotonin (5-HT)
serotonin syndrome
side-chain amine
SNRI (selective norepinephrine reuptake inhibitor)
terminal buttons
tonic release
tricyclic antidepressants
tryptamine – also called indolamine
tryptophan
tyrosine
varicosities

NOTES

300+ types
- Most Common In Brain
  - Glutamate 90%
  - GABA 9%
- Other 1%
  - Monoamines
    - Dopamine
    - Norepinephrine
    - Epineprine
    - Serotonin
  - Acetylcholine
Monoamines
- 1. Catecholamines
  - Most abundant catecholamines
    - Epinephrine (adrenaline)
    - Norepinephrine (noradrenaline)
    - Dopamine
  - Molecules with a catechol nucleus
  - Benzene ring
    - 2 hydorxal side groups
    - Intermediate ethyl chain
    - 1 side-chain amine
    - Catechol
  - Dopamine
    - Derived from tyrosine
      - Dopamine
      - Nor-epinephrine
      - Epinephrine (adrenaline)
    - Tyrosine eaten or synthesized
      - Sent to catecholamine-secreting neurons
      - Water-soluble
      - 50% bound to plasma proteins
        
        circulate in bloodstream
    - In blood, half-life of a few minutes
    - Degraded either by COMT
      - (catechol-O-methyltransferases)
      - Or degraded by MAO
        
        (monoamine oxidases)
        
        Amphetamines and MAOIs bind MAO
        
        Inhibit its action
        
        Stops or slows breaking down
        
        Why amphetamines have longer lifespan than cocaine
    - 5 types of receptors (D1….D5)
      - Also acts as a hormone
      - Released by hypothalamus
      - Inhibits release of prolactin from pituitary
    - Main source
      - Dopaminergic neurons
      - in midbrain
    - Dopamine level modulated by two mechanisms
      - tonic and phasic transmission
      - Tonic release
        
        Small amounts are released
        
        Independent of neurons
        
        Regulates other neurons and neurotransmitter reuptake
        
        Regulates intensity of phasic dopamine response
        
        Sets background level
        
        Sustained release
      - Phasic release
        
        Neurons firing
        
        Short-term activation
        
        single spikes, and rapid bursts
        
        2-6 spikes in quick succession
    - Impacts
      - Cognition and learning
      - Motivation and voluntary movement
      - Sleep, mood, reward, punishment
    - If it’s addictive, it’s dopamine!
    - Controls flow of info
      - Frontal lobe to other areas of brain
      - Metacognition (memory, problem solving)
    - Maybe
      - Teaching signal?
      - Reward-anticipation?
      - Low Levels
        
        Parkinson’s
        
        Can’t give dopamine
        
        (blood-brain barrier)
        
        Give L-Dopa (levodopa);
        
        Hope it’s turned into dopamine
      - High Levels
        
        Euphoria
        
        Orgasm
        
        Reward
        
        Drugs
        
        Nicotine
        
        increases dopamine in mesolimbic reward pathway
        
        Addicts have altered pathways?
        
        Cocaine
        
        Blocks re-uptake
        
        Takes very little stimulation to activate post-synaptic neuron
        
        Cocaine blocks dopamine transporter
        
        Cocaine also blocks norepinephrine transporter
        
        (increase of up to 150 percent)
        
        Cocaine vs. Meth
        
        Both inhibit reuptake
        
        Use different methods
        
        Amphetamines
        
        Structure similar to dopamine
        
        Fool system
        
        Get reuptaken instead
        
        Force dopamine out of terminal buttons
        
        Transporters work in reverse
        
        Pump dopamine out
        
        Schizophrenics
        
        Reduced tonic dopamine release
        
        Over time, causes subsequent phasic dopamine release
        
        Abnormally large responses
        
        Antipsychotic Drugs
        
        Reduce dopamine
        
        Reduce concentration, motivation, pleasure
        
        Increase weight gain, fatigue, stroke, sexual dysfunction
  - Norepinephrine (NE)
    - Also called noradrenaline
    - Synthesized from dopamine
    - Both hormone and neurotransmitter
    - Stress Hormone
      - Released from adrenals into blood
      - Fight or flight response
      - Increasing heart rate
      - Increasing glucose
      - Increasing blood flow to muscles
      - Increases muscle tension
      - Increases vascular tone
      - Triggers compensatory reflex that drops heart rate
      - Reduce brain inflammation
    - In Brain
      - Stored in synaptic vesicles
      - Binds to adrenergic receptors
      - Impacts top-down perceptual processing
    - Signal termination by
      - Degradation
      - Reuptake by norepinephrine transporter
    - NT for sympathetic neurons
      - Regulates the heart
      - Increase in NE, increases contraction rate
    - Impact
      - Top-down perceptual processing
      - Attention
      - Low levels in ADHD
    - ********************
    - To Increase dopamine levels
      - Ritalin/Concerta
      - Dexedrine
      - Adderall
    - SNRI (selective norepinephrine reuptake Inhibitor)
      - Strattera (for ADHD)
      - Doesn’t also impact dopamine
    - Antidepressants
      - Increase NE and Serotonin
        
        Effexor
        
        Cymbalta
    - NE transporter might also reuptake some dopamine
    - *************************
  - Epinephrine
    - Hormone & Neurotransmitter
    - Also called adrenaline
    - As hormone
      - Associated with fear
      - Arouse body
        
        increases heart rate, constricts blood vessels, dilates air passages
    - Given to treat
      - Cardiac arrest
      - Anaphylaxis
      - Superficial bleeding
      - Has been used for
        
        Bronchospasm
        
        Hypoglycemia
        
        Now use
        
        Salbutamol (synthetic epinephrine)
        
        Dextrose
    - Local anesthetic injections
      - Add epinephrine to retard absorption
      - Bupivacaine
      - Lidocaine
    - Easily binds to most adrenergic receptors
      - Inhibits insulin secretion
      - Stimulate liver and muscles
      - Stimulates pancreas to release glucose
      - Stimulates pancreas to release ACTH
      - Regulates cortisol
    - Epinephrine Path
      - Tyrosine
      - L-DOPA
      - Dopamine
      - Norepinephrine
      - Epinephrine
    - Physiologic triggers
      - Noise & bright lights
      - Physical threat
      - Excitement
      - Hot rooms
    - “Adrenaline junkie”
      - Getting “high” on life
      - Dangerous activities
      - Always overwhelmed
      - Need for emergency
      - Endorphins released too
- 2. Indolamine
  - Tryptamine – also called indolamine
    - Serotonin
  - Serotonin (5-HT)
    - Regulates pain and stress
    - Opiate-like
    - Tryptophan
      - helps body produce niacin (B3)
    - Needed to produce serotonin
    - Serotonin is converted into melatonin
    - Stored in intestines
    - Released by liver into blood
    - Binds to platelets
      - When platelets bind to a clot, give off serotonin
    - Vasoconstrictor
      - Regulates clotting
      - Wound healing
    - In Brain
      - 5-HT released from varicosities
      - Not terminal buttons
      - Varicosities
      - Axon can have long chains of swellings
      - Near terminal branches
    - Receptors
      - At least 9 types
      - 5-HT3 is ion gate
      - All others are G-protein regulated
    - Impact
      - Regulate release of insulin
      - Mating behavior of males
      - Regulate growth
      - Regulate intestinal movements
      - Regulate mood, sleep, appetite
      - Serotonin regulates intensity of mood
      - Not change mood itself
      - Change perception of depression
      - Change perception of phobia
    - Too Much
      - In peripheral areas
        
        Sudden increase is painful
        
        Venom of wasps and scorpions
      - In Brain
        
        LSD
        
        Visual hallucinations
        
        Psychedelic drugs increase serotonin
        
        Psilocin-Psilocybin, DMT, Mescaline, LDS
        
        MDNA (ecstasy), Mephedrome release serotonin
    - Low Levels
      - Depression
      - Prozac increases serotonin
      - Inhibits reuptake of 5-HT
      - Sudden Infant Death Syndrome (SIDS)
        
        Defective serotonin signaling?
        
        Not enough serotonin in brain stem, drop in heart rate?
      - To Increase
        
        Stop from breaking down
        
        Inhibit MAO wth MAOI
        
        Stop reuptake
        
        Inhibit reuptake with SSRI
        
        Tricyclic antidepressants
        
        Inhibit reuptake
        
        Serotonin
        
        Norepinephrine
    - Problems?
      - Chronic use of SSRI
      - Might lover baseline levels
      - Even if increase serotonin
      - Worse than when started
      - Switched meds usually resets it
    - Serotonin Syndrome
      - Extremely high levels
        
        toxic and potentially fatal effects
      - To avoid too much of one:
      - SSRI & MAOI taken together
- Acetylcholine (Ach)
  - First neurotransmitter identified
    - small molecule substances
    - similar to amino acids but structurally different
  - Activates muscles
  - Impacts
    - Peripheral nervous system (PNS)
    - Central nervous system (CNS)
    - Major neurotransmitter in autonomic nervous system (ANS)
  - Inhibitory neurotransmitter
    - Slows heart rate
  - Excitatory neurotransmitter
    - Neuromuscular synapses
  - Activates Muscles
    - Binds to receptors
    - Opens sodium channels
    - Sodium ions enter muscle cell
    - Starts sequence that produces muscle contraction
  - Inhibits Heart Muscle
    - Different receptor
    - muscaninic
  - In CNS
    - Neuromodulator
    - Impact plasticity, arousal, reward
    - Enhances senses when wake up
    - Help us pay attention
    - Promotes REM sleep
    - Impacts short term memory
    - Increases response to sensory $
    - Facilitates transmission from thalamus to cortex
    - Reporting expected uncertainty?
  - Low Levels
    - Alzheimer’s disease
  - Two main receptor types
  - 1. Nicotinic Acetylcholine Receptors (AChR)
    - Ionotrophic
    - Sodium, potassium and chloride
    - Muscle and neuron types
      - Curare blocks muscle type
        
        Stops quick effects
      - Myasthenia gravis
        
        Muscle weakness and fatigue
        
        Body produces antibodies against acetylcholine nicotinic receptor
        
        Inhibits acetylcholine signal transmission
        
        Destroys motor end plate
  - 2. Muscaninic Acetylcholine Receptors (mAChR)
    - Metabotrophic
    - In heart, lungs, sweat glands
    - Blocked by atropine
      - Deadly Nightshade
        
        Poison-tipped arrows
        
        Increases pupil size
        
        For attractiveness in past
    - Sometimes used in cataract surgery
      - Causes pupil constriction
      - Miochol-E (CIBA Vision)

QUIZ

6. Neurotransmitters

This is your brain on drugs, naturally.

AUDIO

SLIDES

SLIDES

TERMS

NOTES

QUIZ

VIDEO

DISCUSSION ITEM

This is your brain on drugs, naturally.

AUDIO

SLIDES

SLIDES

TERMS

NOTES

QUIZ

VIDEO

DISCUSSION ITEM

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