LIVE INTERACTIVE LEARNING @ YOUR DESKTOP March 24, 2011 Understanding the Brain: What Drugs Can Tell...

LIVE INTERACTIVE LEARNING @ YOUR DESKTOP

March 24, 2011

Understanding the Brain: What Drugs Can Tell Us

Presented by: Dr. Rochelle D. Schwartz-Bloom

NSTA Webinar-Understanding the Brain...NSTA Webinar-Understanding the Brain... RD Schwartz-BloomRD Schwartz-Bloom

Understanding the Brain: Understanding the Brain: What Drugs Can Tell UsWhat Drugs Can Tell Us

Rochelle D. Schwartz-Bloom, Ph.D.Professor of Pharmacology

Duke University Medical Center


A Web Seminar to Support the A Web Seminar to Support the NIH Curriculum Supplement: The NIH Curriculum Supplement: The

BrainBrain


Localization of Brain FunctionLocalization of Brain Function


Each lobe has key functionsEach lobe has key functions


Prefrontal lobe: matures around age 24!Prefrontal lobe: matures around age 24!

cognitioncognition

memorymemory

impulse control

impulse control

motivationmotivation

judgmentjudgment


The limbic system: integrates emotionsThe limbic system: integrates emotions with body functions with body functions

learningmemory

learningmemory

sensory-motor integration

sensory-motor integration

moodfear

moodfear

attentional processing

attentional processing

memorymemory


Alzheimer’s Disease: Degeneration of Alzheimer’s Disease: Degeneration of basal forebrain & hippocampal neuronsbasal forebrain & hippocampal neurons


The basal gangliaThe basal ganglia

movementinitiation

movementinitiation


pleasureeuphoria

pleasureeuphoria motivationmotivation


Parkinson’s Disease: Degeneration of Parkinson’s Disease: Degeneration of neurons in the basal ganglianeurons in the basal ganglia

movementinitiation

movementinitiation



Addiction: Dysfunction in the basal Addiction: Dysfunction in the basal ganglia ganglia

& prefrontal cortex& prefrontal cortex

pleasureeuphoria

pleasureeuphoriamotivationmotivation

impulse control

impulse control


The hypothalamus: master regulatorThe hypothalamus: master regulator

breathingbreathing

heart rateheart rate

body tempbody temp fluid volume

fluid volume

feedingfeeding

sexual activity

sexual activity

circadian rhythms

circadian rhythms

hormone secretion

hormone secretion


In a unit on “memory”, your students learn that both In a unit on “memory”, your students learn that both alcohol and marijuana can cause problems with alcohol and marijuana can cause problems with

short-term memory. short-term memory. On which area of the brain would the unit focus?On which area of the brain would the unit focus?

A. BrainstemB. AmygdalaC. CerebellumD. HippocampusE. Hypothalamus

Test your knowledge!Test your knowledge!


Let us Pause Two Minutes for Let us Pause Two Minutes for QuestionsQuestions


Region to region Region to region communicationcommunication

“Neuron pathways”“Neuron pathways”


Neurons communicate informationNeurons communicate information


The neuron…end to endThe neuron…end to end


Communication happens at the Communication happens at the synapsesynapse


Neurotransmitter pathwaysNeurotransmitter pathways

Dopamine(pleasure)

Dopamine(pleasure)

Norepinephrine(arousal)

Norepinephrine(arousal)

GABA(sleep)

GABA(sleep)

Glutamate(learning)

Glutamate(learning)

Serotonin(mood)

Serotonin(mood)

Acetylcholine(memory)

Acetylcholine(memory)


The major dopamine pathwayThe major dopamine pathwayPleasure, motivation, movement, Pleasure, motivation, movement,

cognitioncognition


Dopamine is a key neurotransmitter in the Dopamine is a key neurotransmitter in the reward pathwayreward pathway


Brain function is generated by the communication Brain function is generated by the communication among neurons via pathways. Which of the following among neurons via pathways. Which of the following

pathways is affected when neurons degenerate in pathways is affected when neurons degenerate in Parkinson’s Disease? Parkinson’s Disease? A. Serotonin

B. GABAC. DopamineD. GlutamateE. Acetylcholine



Physiology of the NeuronPhysiology of the Neuron(a little chemistry, physics, and (a little chemistry, physics, and

biology)biology)


Neurons communicate electrically & Neurons communicate electrically & chemicallychemically

The impulse is initiated at the beginning of the axonThe impulse is initiated at the beginning of the axon


Ion distribution defines membrane Ion distribution defines membrane potentialpotential

NaNa++ KK++ ClCl--

-70 mv-70 mv

outsideoutside

insideinside

= other anions

- - - - - - - - - - - - - - -

+++++++


Neurons fire impulses based on the Neurons fire impulses based on the membrane potential membrane potential

HyperpolarizedHyperpolarized DepolarizedDepolarized

-70 mv-70 mv-90 mv-90 mv ++30 mv30 mv

RestingResting

++++++ ++++++ ++++++

- - - - - - - - -

- - - - - -

- +++ - +++++

Doesn’t fireDoesn’t fire Will fireWill fire


Impulse generation & conductionImpulse generation & conductionSodium (NaSodium (Na++) channels are key) channels are key


Action potential: NaAction potential: Na++ in then K in then K++ out out

mv


Myelin speeds conduction of electrical Myelin speeds conduction of electrical impulseimpulse

Oligodendrocyte in CNSSchwann cell in PNS


You’ve decided to tell your biology students that You’ve decided to tell your biology students that physics and chemistry play a big role in the physics and chemistry play a big role in the

physiology of neurons (i.e., how they work). physiology of neurons (i.e., how they work).

Which ions are major contributors to the voltage Which ions are major contributors to the voltage potential across a biological membrane?potential across a biological membrane?


K+ Cl- Ca2+ Na+ Mg2+


Synaptic Synaptic NeurotransmissionNeurotransmission

Electrical to chemical to electricalElectrical to chemical to electrical


The synapse: Where neurons The synapse: Where neurons communicatecommunicate


The dopamine synapse: The dopamine synapse: Neuron releases dopamineNeuron releases dopamine


Transporters remove dopamine back into Transporters remove dopamine back into neuronneuron


The serotonin synapse: The serotonin synapse: Neuron releases serotonin Neuron releases serotonin


The acetylcholine synapse: The acetylcholine synapse: Neuron releases acetylcholine Neuron releases acetylcholine


Ion channels open to produce electrical Ion channels open to produce electrical currentscurrents


Review: Steps in neurotransmissionReview: Steps in neurotransmission

Inhibitsaction potentials

Inhibitsaction potentials

Summation triggers

action potentials

Summation triggers

action potentials

Change in membrane potential

Change in membrane potential

Receptor bindingReceptor binding

Terminal membranedepolarizes


Why do you think neurons need both electrical Why do you think neurons need both electrical and chemical signals to communicate to each and chemical signals to communicate to each

other?other?


A. Chemicals can’t travel down axonsB. Electrical impulses can’t jump across the synaptic spaceC. Electrical currents can’t spread far enoughD. Chemicals only affect neurons locally


How Psychoactive Drugs How Psychoactive Drugs WorkWork


Drugs change neurotransmission…Drugs change neurotransmission…one way or anotherone way or another


How do drugs work in the brain?How do drugs work in the brain?

Drugs mimic, stimulate or reduce Drugs mimic, stimulate or reduce the actions of our the actions of our

neurotransmitters to change the neurotransmitters to change the firing rate of neuronsfiring rate of neurons

…….but how?.but how?


Drugs act at a target: proteinsDrugs act at a target: proteins

• ReceptorsReceptors

• Ion channelsIon channels

• TransportersTransporters

• EnzymesEnzymes


Nicotine acts at acetylcholine receptor-Nicotine acts at acetylcholine receptor-ion channels to increase firing rate of ion channels to increase firing rate of

neuronsneurons


Alcohol acts at GABA receptor-ion Alcohol acts at GABA receptor-ion channels to decrease firing rate of channels to decrease firing rate of

neuronsneurons


Oxycontin™ acts at opioid receptors to Oxycontin™ acts at opioid receptors to decrease firing rate of neuronsdecrease firing rate of neurons


Cocaine blocks dopamine transportersCocaine blocks dopamine transporters(more dopamine binds receptors)(more dopamine binds receptors)


Your students know that you took this course Your students know that you took this course and want to know how marijuana works. You tell and want to know how marijuana works. You tell

them that the THC in “pot” works similarly to them that the THC in “pot” works similarly to morphine. It binds to a target to change the morphine. It binds to a target to change the

neuron firing rate.neuron firing rate.

Which is the target and what happens to the Which is the target and what happens to the firing rate?firing rate?


A. THC transporter increases firingB. THC ion channel increases firingC. THC ion channel decreases firingD. THC receptor decreases firing


Drug Addiction: A Brain Drug Addiction: A Brain DiseaseDisease


Pathway in the brain for pleasure (reward)Pathway in the brain for pleasure (reward)

From: SEEK about Tobacco


How do we know?How do we know?

rat self-injects addictingdrugs…and only into rewardareas

From: SEEK about Tobacco at www.rise.duke.edu/seek


Which drugs do rats self-inject?Which drugs do rats self-inject?

Cocaine

Fluoxetine (Prozac™)

Morphine

Alcohol

Diazepam (Valium™)

LSD

Amphetamines

THC

Sugar

From: SEEK about Tobacco


With chronic use of addictive drugs, With chronic use of addictive drugs, behavioral adaptations occurbehavioral adaptations occur

ToleranceTolerance

DependenceDependence

AddictionAddiction

Reduced effect….increase the dose

Function is normal with drug; withdrawal reaction without

Compulsive use, loss of control, craving


With chronic use of addictive drugs, With chronic use of addictive drugs, neuronal adaptations occurneuronal adaptations occur

Neurotransmitter levels change

Neurotransmitter levels change

Receptors up- or down-regulate

Receptors up- or down-regulate

Transporters down-regulate

Transporters down-regulate

Chromatin structure changes

Chromatin structure changes

Dendrite spines increase or decrease

Dendrite spines increase or decrease

Altered neurogenesisAltered neurogenesis

Repeated use of drugRepeated

use of drug


Chronic nicotine increases acetylcholine Chronic nicotine increases acetylcholine (nicotinic) receptors in the brain(nicotinic) receptors in the brain


Dopamine receptors are decreasedDopamine receptors are decreased in reward pathway of drug abusersin reward pathway of drug abusers

Volkow et al., 2004


Amphetamines increase dendritic Amphetamines increase dendritic spinesspines

normal

Meth

Robinson et al., 2001


Adaptations occur in diseaseAdaptations occur in disease

Congestive heart failure

Addiction

dopamine decreases norepinephrine increases

DA receptors decrease β-receptors decrease

dendrites change structure myofibrils change structure

synapses remodel muscle cells remodel

chromatin remodels chromatin remodels

dysfunctional prefrontal cortex dysfunctional ventricle


Can nicotine change your brain? You bet! Can nicotine change your brain? You bet! Which of the following changes occur with Which of the following changes occur with

repeated use of nicotine?repeated use of nicotine?


More nicotinic receptors

More dendritic spines

Altered chromatin structure

Altered dopamine

release

Fewer dopamine receptors


Websites

The Pharmacology Education Partnership (PEP) Project www.thepepproject.net

The Alcohol Pharmacology Education Partnership (APEP) www.rise.duke.edu/apep

Science Education Enhances Knowledge (SEEK) About Tobacco www.rise.duke.edu/seek

NIDA Teaching Packets http://www.drugabuse.gov/pubs/teaching

NIH Supplement: The Brain—Understanding Neurobiology through the Study of Addiction http://science-education.nih.gov/customers.nsf/HSAddiction.htm

Videos

Animated Neuroscience & The Actions of Nicotine, Cocaine & Marijuana www.films.com in the Brain (G Gross de Nunez & RD Schwartz-Bloom)

Additional Resources for High School Additional Resources for High School TeachersTeachers

http://www.thepepproject.net/

http://www.rise.duke.edu/apep

http://www.rise.duke.edu/seek

http://www.drugabuse.gov/pubs/teaching

http://science-education.nih.gov/customers.nsf/HSAddiction.htm

http://www.films.com/


Additional Image CreditsAdditional Image Credits

Brain Anatomy : Slides 4-11, 19, 25-29 From or adapted from Purves et al., (2001) Neuroscience (Sinauer, Inc.)

The Neuron: Slides 16, 17Adapted from www.rise.duke.edu/resources.html (Understanding FASD) (Illustration by Mark Williams)

Synapses: Slides 33-36, 43,45, 48, 49Adapted from RD Schwartz-Bloom for NIDA.See http://www.drugabuse.gov/pubs/teaching/Teaching4/Teaching.html

Acetylcholine Synapses: Slides 37, 38, 46From GG Gross de Nunez and RD Schwartz-Bloom. Animated Neuroscience & the Actions of Nicotine, Cocaine, & Marijuana in the Brain (www.films.com)

http://www.rise.duke.edu/resources.html

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LIVE INTERACTIVE LEARNING @ YOUR DESKTOP March 24, 2011 Understanding the Brain: What Drugs Can Tell...

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