DO NOW
• List these items in order of occurrence…starting
at neurotransmitter release
• Action potential travels down the axon to the
axon terminal
• Neurotransmitter release (again)
• Cell body
• Binds to receptors on the dendrite
• Receptor activates cell and causes action
potential
Last Week
• Parts and functions of the brain
Basic points from last week
• A neurotransmitter will either:
– Increases activity (more action potentials)
• Will release neurotransmitters
– Decreases activity (less action potentials)
• Will not release neurotransmitters (or release less)
• This is the major take home
– The details of the action potential are much less
important
In other words…
• Just understand the flow of information
– Axon terminal releases neurotransmitter
– Neurotransmitter binds to receptor on dendrite
– This either prevents or allows the cell to fire an action
potential
– If it allows an action potential to occur…it travels down to
the axon terminal and…
– Axon terminal releases neurotransmitter…
– Neurotransmitter binds to receptor on dendrite…
– Etc
Neuron
• Dendrites – “receive
input”
• Axon – “sends output”
• Information travels from
dendrites to axon!
• Question is: How?
Neurotransmitters
Does one of two things
Makes a neuron fire an action potential
Prevents a neuron from firing an action
potential
Another example
A
B
We say the flow of information is
going from cell A to D
C
D
Another example
A
B
C
In this case, cell B is a GABA neuron, and release
GABA. This shuts down cell C, which can no longer
fire an action potential.
D
For your paper
• Understand the broader picture of what an action
potential is.
– Whenever a neuron fires one, it will release
neurotransmitters
• Drugs of abuse either
– increase firing of action potentials (excitatory effect)
– Decrease firing of action potentials (inhibitory effect)
– OR…alter neurotransmitters in some way
A concrete example of how neurons
communicate:
• Thermoreceptor cells (i.e. they detect hot and cold)
– Live in your skin.
– When temperature falls below a threshold (let’s say 60oF, these cells
become “activated”.
– These cells have axons that project all the way to your spinal cord
• They release glutamate from their axon terminals (when the temperature falls
below 60) onto the spinal cord neurons dendrites.
• Spinal cord neurons become activated!
• Spinal cord have axons that travel to thalamus(relay station)
• Spinal cord neurons release glutamate, from their axon terminals, onto the
dendrites of thalamus neurons
• Thalamus neurons have axons that project to the parietal lobe.
• When thalamus neurons are excited by spinal cord neurons, thalamus neurons
release glutamate onto the dendrites of parietal lobe neurons.
• When parietal lobe neurons are excited, then you feel cold.
A second example
• You want to move your arm.
– Frontal lobe neurons have axons that release
glutamate onto motor neurons.
– Motor neurons live in the spinal cord
– Motor neurons have axons that release
acetylcholine (excitatory) onto your muscles,
which cause them to contract.
It is complicated
• If things are fuzzy—it is ok.
– We kind of just figured this out 50 years ago, and
we still do not really understand it.
This week
• What is a neurotransmitter?
– Different types
• How are they created? Released? Stored?
Degraded?
• Receptors
– Different types of receptors
Today’s Goals
• (1) You will become familiar with the major
neurotransmitters in the brain.
• (2) You will be able to describe how neurotransmitters
are released from the axon terminal and how they
interact with receptors.
• (3) You will be able to predict what happens to
dopamine levels in the brain when given a drug of
abuse.
– Ultimately—this matters the most. All drugs of abuse alter
dopamine levels.
Video
• http://www.youtube.com/watch?v=p5zFgT4a
ofA
Neurotransmitters
• Released from the
axon terminals
• Bind to receptors on
dendrites
Why do neurotransmitters get
released?
Action potentials, which start at the
dendrite, travels down the cell body,
down the axon, down the axon terminal,
and causes neurotransmitters to be
released.
Causes vesicles, which contain
neurotransmitters, to be released into
the synapse.
Video again
• http://www.youtube.com/watch?v=p5zFgT4a
ofA
Drug and Alcohol Abuse
Neurotransmission
Neurotransmitters
• Stored in vesicles
• Two major types:
Each neurotransmitter
has a unique shape
Neurotransmitters
Does one of two things
Makes a neuron fire an action potential
(excitatory)
Prevents a neuron from firing an action
potential (inhibitory)
Receptors
• Allow neurotransmitters to a have their effect
on a neuron
How do receptors and
neurotransmitters interact?
• Key (ligand, neurotransmitter) and Lock
(receptor)
Receptors
• Embedded in the cell’s membrane
• Like neurotransmitters, have a specific shape
• The shape of a neurotransmitter complements
the shape of the receptor
– Exactly like a lock and key
In reality…
• What determines whether or not a
neurotransmitter will be excitatory or inhibitory is
• THE RECEPTOR
• This is why using terms like “excitatory and
inhibitory” neurotransmitters can be misleading.
– For example: There exist glutamate receptors, when
bound by glutamate, are inhibitory.
What happens after a
neurotransmitter binds to a receptor?
• Does it just stay bound?
• Nope…that would be bad.
Neurotransmitter removal
• Two ways
• Reuptake
– Proteins grab the neurotransmitters and bring
them back into the axon terminal
• Enzyme degradation
– Neurotransmitter gets destroyed while in the
synapse
Reuptake
• “taken back up”
– Transporters are proteins that take the
neurotransmitters back from the synapse into the
axon terminal
Enzymatic Degradation
• An enzyme (which is a protein) cuts up the
neurotransmitter into pieces
• Can no longer bind to receptor in this state
Summary
• Neurotransmitters are
released from synaptic
vesicles into the synapse
• Bind to receptors
• Excite or inhibit the post
synaptic cell
• Get taken out of the synapse
• Repackaged in vesicles for
future release
Individual Neurotransmitters
• For this class you need to know
– Glutamate
– GABA
– Acetylcholine
– Dopamine (all drugs of abuse affect this)
– Serotonin
– Norepinephrine
Glutamate
• Receptors basically on every single neuron in
the brain
• Taken up by reuptake
– Not enzymatic degradation
Glutamate functions
• Major excitatory neurotransmitter
• Glutamate receptors are basically on every cell
• Cleared by reuptake
GABA
• Inhibitory
• Balances out the excitatory nature of
glutamate
• Acts on GABA receptors
• Cleared by reuptake
Balance
• You need to balance excitation and inhibition
to equal out…
– Seizures (too much excitation)
– Paralysis (too much inhibition)
Acetylcholine function
• Learning, memory, attention (CNS)
• Motor movement (PNS)
amanita muscaria
– Some mushrooms are hallucinogens…mimics effect of
acetylcholine
Acetylcholine elimination
• Enzymatic Degradation
– Acetylcholinesterase
Toxins and Acetylcholine
• Black Widow venom
– Massively release acetylcholine throughout the
PNS
– Causes muscle pain, vomiting, nausea
• Botox
– BLOCKS acetylcholine release
– This causes paralysis of the muscles
Group Discussion
• In your group, discuss what would happen if
you gave a drug which prevented
acetylcholinesterase from doing its job.
• Talk about in terms of whether there will be
more or less acetylcholine in the synapse
• What would happen to your muscles?
Monoamines
• Dopamine
• Serotonin
• Norepinephrine
Serotonin
Turkey
Removal
• Two ways
– Reuptake
• Serotonin Transporter
– SSRIs
– Serotonin selective reuptake inhibitor
– what happens to the amount of serotonin in the synapse if
you inhibit (block) the serotonin transporter
– Enzymatic degradation
• Monoamine oxidase
– Monoamine oxidase inhibitors (MAOIs)
Group Question
• What is the effect of Serotonin Selective
Uptake Inhibitors?
• Do they make you happier or sad?
• What does this say about the role of
serotonin?
Dopamine
• Most important neurotransmitter in
addiction!
Dopamine
• Directly affects by cocaine, amphetamines,
and antidepressant meds
• Synthesized from dietary tyrosine
– TyrosineL-DOPADA
• Salience, reward, motivation, novelty,
unpredictable events
Dopamine neurons
• Live in two brain areas
• Ventral Tegmental Area
– Releases dopamine in the nucleus accumbens
• Substantia Nigra
– Releases dopamine in the striatum
Nigro-Striatal
• Substantia Nigra dopamine release in the
striatum
Meso-Limbic Pathway
Dopamine (DA) receptors
• D1 (“excitatory”)
– Basically everywhere (most concentrated in
striatum, accumbens, prefrontal cortex)
• D2 (“inhibitory”)
– Basically everywhere(most concentrated in
striatum, accumbens, prefrontal cortex)
Dopamine Elimination
• Two ways
– Transporters (i.e. reuptake)
• Dopamine Transporter (DAT)
– Cocaine blocks DAT
– So does ritalin and tricyclic antidepressants
– Enzymatic Degradation
• MAO
– Again…MAOIs
• More specific to dopamine is
– Catechol-O-methyltransferase
Group Question 2
• Monamine oxidase inhibitors (MAOIs) disrupt
the ability of the enzyme monoamine
oxidase…(remember monoamine oxidase breaks
down dopamine and serotonin)
– What does this do to dopamine?
– What does this do to serotonin?
• Given you answer in (4)…what are some
potential problems with a MAOI?
Biological Central Dogma of Addiction
• All drugs of abuse enhance dopamine release
in the nucleus accumbens.
DiChiara and Imperato 1988
Microdialysis: measures
neurotransmitter amount
in a given brain area
Used to measure how
dopamine levels change in
response to multiple
drugs…some abused by
humans, and some not.
All drugs of abuse elevate dopamine
levels in accumbens!!!!!!!!!!!!!!
Nonabused drugs do not alter
dopamine release in the nucleus
accumbens
Next week
• Quiz 1 (Weeks 1-3).
• Pharmacodynamics
–
–
–
–
How do drugs affect you
Lethal doses
How it mimics neurotransmitters (like nicotine and morphine)
How it prevents reuptake (cocaine)
• Pharmacokinetics
– RADME:
•
•
•
•
•
Route of administration (smoking, inhaling, eating)
Absorption (where is it absorbed)
Distribution (how does it get to the brain?)
Metabolism (how is it metabolized? How is broken down in the body)
Elimination (how is it eliminated…mostly through urine...but not totally…)
• Alcohol
• Nicotine
• Marijuana
Pharmacodynamics
• How drugs affect you
Placebo Effect
• Belief about a drug produces desired effect
– Red pills more efficacious than blue pills
– Big pills more efficacious than small pills
• By definition…
– A nonspecific drug effect
Specific versus nonspecific drug effects
How can drugs act in the brain?
Something to think about