Synapses and Drugs[1]

7/28/2019 Synapses and Drugs[1]

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Synapses and Drugs

Raymond S. Broadhead

Brooks School

MCB/HHMI Summer Camp

July, 2005


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Objectives

Review the Synapse

Discuss some drugs and theireffects on thesynapse

Discuss how the altered synapses may

affect the adolescent brain

Play Jeopardy Game on neurobiology


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Review the Synapse

What is a synapse?

A synapse is the gap between the axon of

one nerve and the dendrite of the next one.

The average neuron has 1,000 synapses

with other neurons.


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What does a synapse look like?

Electron Micrograph

Microscopy with

Fluorescent ProteinsMicroscopy with

Fluorescent Proteins

Murthy_HHMI_teachers_2005_sub.ppt


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Figure 48.12 A chemical synapse


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Key to Previous Diagram1. Impulse from action potential opens ion

channels forCa++

2. The increased Ca++ concentration in the axonterminal initiates the release of theneurotransmitter (NT)

3. NT is released from its vesicle and crosses the

gap orsynaptic cleft and attaches to a proteinreceptor on the dendrite


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Key to Diagram (cont.)

4. Interaction ofNT and protein receptoropen post-synaptic membrane ion

channel forNa+

5. After transmission the NT is eitherdegraded by an enzyme or taken back intothe pre-synaptic membrane by atransporter orreuptake pump


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Synapse Animation

To see an animation of a

synapse, clickhere.

Copyright - Pearson Education


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Neurotransmitters

There are dozens of different neurotransmitters

(NT) in the neurons of the body.

NTs can be eitherexcitatory orinhibitory

Each neuron generally synthesizes and releases a

single type of neurotransmitter

The major neurotransmitters are indicated on

the next slide.


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Major Neurotransmitters in the Body

A neurotransmitter involved in many functions including mood, appetite,

and sensory perception. In the spinal cord, serotonin is inhibitory in pain

pathways.

Serotonin

Norepinephrine acts as a neurotransmitter and a hormone. In the

peripheral nervous system, it is part of the flight-or-flight response. In thebrain, it acts as a neurotransmitter regulating normal brain processes.

Norepinephrine is usually excitatory, but is inhibitory in a few brain areas.

Norepinephrine

A neurotransmitter used mainly by neurons in the spinal cord. It probably

always acts as an inhibitory neurotransmitter.

Glycine

The most common excitatory neurotransmitter in the brain.Glutamate

The major inhibitory neurotransmitter in the brain.GABA

(gamma-aminobutyric acid)

The neurotransmitter that produces feelings of pleasure when released by

the brain reward system. Dopamine has multiple functions depending on

where in the brain it acts. It is usually inhibitory.

Dopamine

A neurotransmitter used by the spinal cord neurons to control muscles and

by many neurons in the brain to regulate memory. In most instances,

acetylcholine is excitatory.

Acetylcholine

Role in the BodyNeurotransmitter

NIH Publication No. 00-4871


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Drugs Interfere with

Neurotransmission

Drugs can affect synapses at a variety ofsites and in a variety of ways, including:

1. Increasing number of impulses

2. Release NT from vesicles with or without

impulses

3. Block reuptake or block receptors

4. Produce more or less NT

5. Prevent vesicles from releasing NT


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Three Drugs (of many) which

affect Neurotransmission

Methamphetamine

Nicotine

Alcohol

seattlepi.nwsource.com/ methamphetamines/

science.howstuffworks.com/ alcohol.htm


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Methamphetamine alters Dopamine transmission

in two ways:

1. Enters dopamine vesicles in axon terminal causing

release of NT

2. Blocks dopamine transporters from pumping dopamine

back into the transmitting neuron


seattlepi.nwsource.com/ methamphetamines/


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Result: More dopamine in the

Synaptic Cleft

This causes neurons to fire more often than

normal resulting in a euphoric feeling.


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Problems1. After the drug wears off, dopamine levels drop,

and the user crashes. The euphoric feeling will

not return until the user takes more

methamphetamine2. Long-term use of methamphetamine causes

dopamine axons to wither and die.

3. Note that cocaine also blocks dopamine

transporters, thus it works in a similar manner.

4. To see an animation on cocaine and brain

synapses, clickhere.


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What about Nicotine?

Similar to methamphetamine and cocaine,

nicotine increases dopamine release in a

synapse.

However, the mechanism is slightly

different.

Nicotine binds to receptors on thepresynaptic neuron.


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Nicotine binds to the presynaptic

receptors exciting the neuron to fire more

action potentials causing an increase in

dopamine release.Nicotine also affects neurons by

increasing the number of synaptic

vesicles released.



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How does alcohol affect synapses?

Alcohol has multiple effects on neurons. It

alters neuron membranes, ion channels,

enzymes, and receptors.

It binds directly to receptors for

acetylcholine, serotonin, and gamma

aminobutyric acid (GABA), and glutamate. We will focus on GABA and its receptor.


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GABA and the GABA Receptor

GABA is a neurotransmitter that has aninhibitory effect on neurons.

When GABA attaches to its receptor on thepostsynaptic membrane, it allows Cl- ionsto pass into the neuron.

This hyperpolarizes the postsynapticneuron to inhibit transmission of animpulse.


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Alcohol and the GABA Receptor

When alcohol enters the brain, it binds to

GABA receptors and amplifies the

hyperpolarization effect ofGABA.

The neuron activity is further diminished

This accounts for some

of the sedative affects

of alcohol

science.howstuffworks.com/ alcohol.htm


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The Adolescent Brain and Alcohol

The brain goes through dynamic change during

adolescence, and alcohol can seriously damage

long- and short-term growth processes. Frontal lobe development and the refinement of

pathways and connections continue until age 16,

and a high rate of energy is used as the brain

matures until age 20. Damage from alcohol at this time can be long-

term and irreversible.

From AMA pub 9416


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The Adolescent Brain (cont.)

In addition, short-term or moderatedrinking impairs learning and memory

far more in youth than adults. Adolescents need only drink half as much

as adults to suffer the same negativeeffects.

To see an animation of GABA receptorsand the influence of alcohol, clickhere.


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Drugs That Influence Neurotransmitters

LSD

caffeine

no change in the amount of

neurotransmitter released, or

neurotransmitter cannot bind to

its receptor on postsynaptic

neuron

block receptor with another

molecule

No drug exampleless neurotransmitter releasedprevent vesicles from releasingneurotransmitter

probably does not work this wayless neurotransmitter in synaptic

cleft

produce less neurotransmitter

cocaine

amphetamine

more neurotransmitter present in

synaptic cleft

block reuptake

nicotineincreased neurotransmitter

release

release more neurotransmitter in

response to an impulse

amphetamines

methamphetamines

increased neurotransmitter

release

release neurotransmitter from

vesicles with or without impulses

nicotine, alcohol, opiatesincreased neurotransmitter

release

increase the number of impulses

Drug that acts this wayEffect on Neurotransmitter

release or availability

Change in Neurotransmission



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Review - Jeopardy Game

Clickhere to play neurobiology jeopardy

www.ibiblio.org/.../ greviews/jeop/jeop1.gif


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Resources http://www.pbs.org/w

net/closetohome/home

.html http://www.biologyma

d.com/NervousSystem/synapses.htm#drugs

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Synapses.html

http://science.educatio

n.nih.gov/Customers.n

sf/HSBrain?OpenForm

Biology, Campbell

and Reece, 6th Edition,

Benjamin Cummings,San Francisco, 2002


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More Related Websites to Explore http://faculty.washington.edu/chudler/neurok.html

http://www.teachersdomain.org/

http://science.nhmccd.edu/biol/ap1int.htm http://www.hhmi.org/

http://www.med.harvard.edu/AANLIB/home.html

http://www.med.harvard.edu/publications/On_The

_Brain/


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Acknowledgements

Thank you to all members of the MCB/HHMI

Summer Camp for helping to make this a

great experience. Special thanks to Tara

Bennett, Susan Johnson, and my computer

buddy, Katie Horne.

Synapses and Drugs[1]

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