- 300+ types
- Most Common In Brain
- Glutamate 90%
- GABA 9%
- Other 1%
- Monoamines
- Dopamine
- Norepinephrine
- Epineprine
- Serotonin
- Acetylcholine
- Monoamines
- Most Common In Brain
- 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
- Can’t give dopamine
- Parkinson’s
- 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)
- Blocks re-uptake
- 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
- Structure similar to dopamine
- Derived from tyrosine
- 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
- Increase NE and Serotonin
- 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
- Most abundant catecholamines
- 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
- In peripheral areas
- 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
- Inhibit reuptake
- Stop from breaking down
- 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
- Extremely high levels
- Tryptamine – also called indolamine
- 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
- Curare blocks muscle type
- 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
- Deadly Nightshade
- Sometimes used in cataract surgery
- Causes pupil constriction
- Miochol-E (CIBA Vision)
- First neurotransmitter identified
- 1. Catecholamines
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