Transcript The StarNet Case Control Study

The StarNet Case
Control Study
Nicotine, Neurotransmission,
and the Reward Pathway
University of Washington
Department of Genome Sciences
Where does nicotine go in your body?
It goes to your lungs, and then via the bloodstream to your heart and all
parts of the body, including your brain.
How does the body get rid of nicotine?
• Nicotine circulates
throughout the body in the
bloodstream.
• Eventually it is carried to
the liver, where enzymes
break it down into other
compounds.
• These compounds are
carried by the bloodstream
to the kidneys and then
excreted from the body in
urine.
A look at the brain
Different parts of the brain are involved in different functions, like vision,
movement, thinking, memory.
The reward pathway
The reward pathway is a neural network used for
reinforcing behaviors that are important for survival.
Nicotine also stimulates the reward pathway.
This feels
Eating
makes
me
happy!
good!
To understand how
this works, we need
to learn about
neurons and
neurotransmission...
Neurons
• Have a cell body, dendrites, and axon
• Use electrical impulses and chemical signals
Model of a neuron
Developed by Eric Chudler, Neuroscience for Kids
Electrical impulse
Neurotransmitter 2
Neurotransmitter 1
Axon terminal
Cell body
Dendrite
When neurotransmitter binds to the
dendrites…
Neurotransmission is…
The process of transferring messages between neurons.
Its purpose is to carry signals from one part of the brain
to another or to other parts of the body, like muscles.
Synapse
The Synapse: How neurons talk
to each other
Neurotransmitters are chemical signals that transfer a
message from one neuron to the next across the synapse.
Transmitting neuron
Receiving neuron
Dopamine is the neurotransmitter in the
reward pathway
Stimulation of neurons in the ventral tegmental area results in
release of dopamine in the nucleus accumbens (emotional
center) and the prefrontal cortex (thinking).
Dopamine levels are tightly controlled
through its synthesis, breakdown, and recycling
back into vesicles.
DDC
TH=Tyrosine hydroxylase
DOPA=dihydrophenylalanine
DDC=DOPA decarboxylase
DR=Dopamine receptor
DT=Dopamine transporter
COMT=Catechol-O-methyltransferase
MAO=Monoamine oxidase
Nicotine replaces the neurotransmitter,
acetylcholine, in the reward pathway
1. Normally, acetylcholine
binds to its receptor on
neurons in the VTA,
leading to release of
dopamine in the
nucleus accumbens
(NA) and prefrontal
cortex (PC).
2. Nicotine also binds
to acetylcholine
receptors in the
VTA, resulting in
dopamine release
in the NA and PC.
How does nicotine interact with
neurotransmission and the reward pathway?
This
feels
good!
1. Nicotine binds to acetylcholine
receptors in the ventral
tegmental area.
2. An electrical impulse
travels down the neuron
axon.
3-4. Dopamine is released at
axon terminals in the
nucleus accumbens and
prefrontal cortex.
5. Dopamine binds to dopamine
receptors on other neurons.
6. This leads to increase or
decrease in electric impulse on
receiving neuron, resulting in the
rewarding effects often reported
by smokers.
7. Dopamine is reabsorbed through
dopamine transporter.
What is the impact of nicotine
interacting with the reward
pathway?
Addiction!
What genes might be involved in differences
in smoking behavior?
On Student Sheet A3.3, circle the
proteins that might account for
differences in smoking behavior.
DDC
The reward pathway is involved in
other addictive behaviors
• Cocaine slows the re-uptake of
dopamine in the nucleus
accumbens.
• Methamphetamine results in
increased dopamine release
as well as blocking the reuptake of dopamine in the
nucleus accumbens.
• Other addictive behaviors, like
gambling and risk-taking
involve the reward pathway.
What are some benefits of identifying
variants in genes associated with
smoking behavior?
• Increasing our understanding of the addiction process
• Helping people understand their own risk for becoming
addicted to nicotine, which may motivate them to quit
smoking or never begin
• Helping people choose the best cessation program based
on their genes
What are some drawbacks of
identifying variants in genes associated
with smoking behavior?
• The same gene variants may also be associated with the
use of other addictive drugs or addictive behaviors. By
learning about genes that affect smoking behavior,
people may get unwanted information about other
behaviors. A gene that affects different traits is called
pleiotropic.
• People who carry a risk variant may face discrimination
getting jobs, health insurance, or life insurance.
• The frequency of a risk variant may be higher in a certain
group, leading to stigmatization of that group.