Synapses and Drugs

Raymond S. Broadhead

Brooks School

MCB/HHMI Summer Camp

July, 2005

Objectives

• Review the Synapse

• Discuss some drugs and their effects on thesynapse

• Discuss how the altered synapses mayaffect the adolescent brain

• Play “Jeopardy Game” on neurobiology

Review the Synapse

• What is a synapse?

• A synapse is the “gap” between the axon ofone nerve and the dendrite of the next one.

• The average neuron has 1,000 synapseswith other neurons.

What does a synapse look like?

Electron Micrograph

Microscopy withFluorescent ProteinsMicroscopy with

Fluorescent Proteins

Murthy_HHMI_teachers_2005_sub.ppt

Figure 48.12 A chemical synapse

Key to Previous Diagram

1. Impulse from action potential opens ionchannels for Ca++

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” or synaptic cleft and attaches to a proteinreceptor on the dendrite

Key to Diagram (cont.)

4. Interaction of NT and protein receptoropen post-synaptic membrane ionchannel for Na+

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

Synapse Animation

To see an animation of asynapse, click here.

Copyright - Pearson Education

Neurotransmitters

• There are dozens of different neurotransmitters(NT) in the neurons of the body.

• NTs can be either excitatory or inhibitory

• Each neuron generally synthesizes and releases asingle type of neurotransmitter

• The major neurotransmitters are indicated onthe next slide.

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 painpathways.

Serotonin

Norepinephrine acts as a neurotransmitter and a hormone. In theperipheral 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 probablyalways 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 bythe brain reward system. Dopamine has multiple functions depending onwhere in the brain it acts. It is usually inhibitory.

Dopamine

A neurotransmitter used by the spinal cord neurons to control muscles andby many neurons in the brain to regulate memory. In most instances,acetylcholine is excitatory.

Acetylcholine

Role in the BodyNeurotransmitter

NIH Publication No. 00-4871

Drugs Interfere withNeurotransmission

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

1. Increasing number of impulses2. Release NT from vesicles with or without

impulses3. Block reuptake or block receptors4. Produce more or less NT5. Prevent vesicles from releasing NT

Three Drugs (of many) whichaffect Neurotransmission

Methamphetamine

Nicotine

Alcohol

seattlepi.nwsource.com/ methamphetamines/

science.howstuffworks.com/ alcohol.htm

Methamphetamine alters Dopamine transmissionin 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

NIH Publication No. 00-4871

seattlepi.nwsource.com/ methamphetamines/

Result: More dopamine in theSynaptic Cleft

• This causes neurons to fire more often thannormal resulting in a euphoric feeling.

Problems……1. After the drug wears off, dopamine levels drop,

and the user “crashes”. The euphoric feeling willnot return until the user takes moremethamphetamine

2. Long-term use of methamphetamine causesdopamine axons to wither and die.

3. Note that cocaine also blocks dopaminetransporters, thus it works in a similar manner.

4. To see an animation on cocaine and brainsynapses, click here.

What about Nicotine?

• Similar to methamphetamine and cocaine,nicotine increases dopamine release in asynapse.

• However, the mechanism is slightlydifferent.

• Nicotine binds to receptors on thepresynaptic neuron.

•Nicotine binds to the presynapticreceptors exciting the neuron to fire moreaction potentials causing an increase indopamine release.

•Nicotine also affects neurons byincreasing the number of synapticvesicles released.

NIH Publication No. 00-4871

How does alcohol affect synapses?

• Alcohol has multiple effects on neurons. Italters neuron membranes, ion channels,enzymes, and receptors.

• It binds directly to receptors foracetylcholine, serotonin, and gammaaminobutyric acid (GABA), and glutamate.

• We will focus on GABA and its receptor.

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.

Alcohol and the GABA Receptor

• When alcohol enters the brain, it binds toGABA receptors and amplifies thehyperpolarization effect of GABA.

• The neuron activity is further diminished

• This accounts for some

of the sedative affects

of alcohol

science.howstuffworks.com/ alcohol.htm

The Adolescent Brain and Alcohol

• The brain goes through dynamic change duringadolescence, and alcohol can seriously damagelong- and short-term growth processes.

• Frontal lobe development and the refinement ofpathways and connections continue until age 16,and a high rate of energy is used as the brainmatures until age 20.

• Damage from alcohol at this time can be long-term and irreversible.

From AMA pub 9416

The Adolescent Brain (cont.)

• In addition, short-term or moderatedrinking impairs learning and memoryfar more in youth than adults.

• Adolescents need only drink half as muchas adults to suffer the same negativeeffects.

• To see an animation of GABA receptorsand the influence of alcohol, click here.

Drugs That Influence Neurotransmitters

LSD

caffeine

no change in the amount ofneurotransmitter released, or

neurotransmitter cannot bind toits receptor on postsynaptic

neuron

block receptor with anothermolecule

No drug exampleless neurotransmitter releasedprevent vesicles from releasingneurotransmitter

probably does not work this wayless neurotransmitter in synapticcleft

produce less neurotransmitter

cocaine

amphetamine

more neurotransmitter present insynaptic cleft

block reuptake

nicotineincreased neurotransmitterrelease

release more neurotransmitter inresponse to an impulse

amphetamines

methamphetamines

increased neurotransmitterrelease

release neurotransmitter fromvesicles with or without impulses

nicotine, alcohol, opiatesincreased neurotransmitterrelease

increase the number of impulses

Drug that acts this wayEffect on Neurotransmitterrelease or availability

Change in Neurotransmission

NIH Publication No. 00-4871

Review - Jeopardy Game

• Click here to play neurobiology jeopardy

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

Resources

• http://www.pbs.org/wnet/closetohome/home.html

• http://www.biologymad.com/NervousSystem/synapses.htm#drugs

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

• http://science.education.nih.gov/Customers.nsf/HSBrain?OpenForm

• Biology, Campbelland Reece, 6th Edition,Benjamin Cummings,San Francisco, 2002

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/

Acknowledgements

Thank you to all members of the MCB/HHMISummer Camp for helping to make this agreat experience. Special thanks to Tara

Bennett, Susan Johnson, and my computer

buddy, Katie Horne.