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Transcript
LIVE INTERACTIVE LEARNING @ YOUR DESKTOP Understanding the Brain: What Drugs Can Tell Us Presented by: Dr. Rochelle D. Schwartz-Bloom March 24, 2011 Understanding the Brain: What Drugs Can Tell Us Rochelle D. Schwartz-Bloom, Ph.D. Professor of Pharmacology Duke University Medical Center NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom A Web Seminar to Support the NIH Curriculum Supplement: The Brain NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Localization of Brain Function NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Each lobe has key functions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Prefrontal lobe: matures around age 24! motivation cognition memory impulse control judgment NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The limbic system: integrates emotions with body functions attentional processing mood fear sensory-motor integration memory NSTA Webinar-Understanding the Brain... learning memory RD Schwartz-Bloom Alzheimer’s Disease: Degeneration of basal forebrain & hippocampal neurons NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The basal ganglia movement initiation motivation pleasure euphoria NSTA Webinar-Understanding the Brain... motivation RD Schwartz-Bloom Parkinson’s Disease: Degeneration of neurons in the basal ganglia movement initiation motivation NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Addiction: Dysfunction in the basal ganglia & prefrontal cortex impulse control motivation NSTA Webinar-Understanding the Brain... pleasure euphoria RD Schwartz-Bloom The hypothalamus: master regulator body temp fluid volume breathing circadian rhythms heart rate sexual activity feeding hormone secretion NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Test your knowledge! In a unit on “memory”, your students learn that both alcohol and marijuana can cause problems with short-term memory. On which area of the brain would the unit focus? A. B. C. D. E. Brainstem Amygdala Cerebellum Hippocampus Hypothalamus NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Let us Pause Two Minutes for Questions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Region to region communication “Neuron pathways” NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Neurons communicate information NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The neuron…end to end NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Communication happens at the synapse NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Neurotransmitter pathways Dopamine (pleasure) Serotonin (mood) Glutamate (learning) Acetylcholine (memory) GABA (sleep) Norepinephrine (arousal) NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The major dopamine pathway Pleasure, motivation, movement, cognition NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Dopamine is a key neurotransmitter in the reward pathway NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Test your knowledge! Brain function is generated by the communication among neurons via pathways. Which of the following pathways is affected when neurons degenerate in Parkinson’s Disease? A. B. C. D. E. Serotonin GABA Dopamine Glutamate Acetylcholine NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Let us Pause Two Minutes for Questions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Physiology of the Neuron (a little chemistry, physics, and biology) NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Neurons communicate electrically & chemically The impulse is initiated at the beginning of the axon NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Ion distribution defines membrane potential outside Na+ K+ Cl- +++++++ -70 mv --------------inside = other anions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Neurons fire impulses based on the membrane potential Hyperpolarized Resting Depolarized ++++++ ++++++ ++++++ -90 mv -70 mv +30 mv ----- - +++ - +++++ -------- Doesn’t fire NSTA Webinar-Understanding the Brain... Will fire RD Schwartz-Bloom Impulse generation & conduction Sodium (Na+) channels are key NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom mv Action potential: Na+ in then K+ out NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Myelin speeds conduction of electrical impulse Oligodendrocyte in CNS NSTA Webinar-Understanding the Brain... Schwann cell in PNS RD Schwartz-Bloom Test your knowledge! You’ve decided to tell your biology students that physics and chemistry play a big role in the physiology of neurons (i.e., how they work). Which ions are major contributors to the voltage potential across a biological membrane? K+ Cl- NSTA Webinar-Understanding the Brain... Ca2+ Na+ Mg2+ RD Schwartz-Bloom Let us Pause Two Minutes for Questions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Synaptic Neurotransmission Electrical to chemical to electrical NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The synapse: Where neurons communicate NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The dopamine synapse: Neuron releases dopamine NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Transporters remove dopamine back into neuron NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The serotonin synapse: Neuron releases serotonin NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom The acetylcholine synapse: Neuron releases acetylcholine NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Ion channels open to produce electrical currents NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Review: Steps in neurotransmission Terminal membrane depolarizes Neurotransmitter release Receptor binding Ion channels open or close Change in membrane potential Excitation or inhibition Summation triggers action potentials NSTA Webinar-Understanding the Brain... Inhibits action potentials RD Schwartz-Bloom Test your knowledge! Why do you think neurons need both electrical and chemical signals to communicate to each other? A. B. C. D. Chemicals can’t travel down axons Electrical impulses can’t jump across the synaptic space Electrical currents can’t spread far enough Chemicals only affect neurons locally NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Let us Pause Two Minutes for Questions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom How Psychoactive Drugs Work NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Drugs change neurotransmission… one way or another NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom How do drugs work in the brain? Drugs mimic, stimulate or reduce the actions of our neurotransmitters to change the firing rate of neurons ….but how? NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Drugs act at a target: proteins • Receptors • Ion channels • Transporters • Enzymes NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Nicotine acts at acetylcholine receptor-ion channels to increase firing rate of neurons NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Alcohol acts at GABA receptor-ion channels to decrease firing rate of neurons NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Oxycontin™ acts at opioid receptors to decrease firing rate of neurons NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Cocaine blocks dopamine transporters (more dopamine binds receptors) NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Test your knowledge! Your students know that you took this course and want to know how marijuana works. You tell them that the THC in “pot” works similarly to morphine. It binds to a target to change the neuron firing rate. Which is the target and what happens to the firing rate? A. B. C. D. THC transporter THC ion channel THC ion channel THC receptor NSTA Webinar-Understanding the Brain... increases firing increases firing decreases firing decreases firing RD Schwartz-Bloom Let us Pause Two Minutes for Questions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Drug Addiction: A Brain Disease NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Pathway in the brain for pleasure (reward) From: SEEK about Tobacco NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom How do we know? rat self-injects addicting drugs…and only into reward areas From: NSTA Webinar-Understanding the Brain... SEEK about Tobacco at www.rise.duke.edu/seek RD Schwartz-Bloom Which drugs do rats self-inject? Cocaine Fluoxetine (Prozac™) Morphine Alcohol Diazepam (Valium™) LSD Amphetamines From: SEEK about Tobacco THC Sugar NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom With chronic use of addictive drugs, behavioral adaptations occur Tolerance Dependence Addiction Reduced effect….increase the dose Function is normal with drug; withdrawal reaction without Compulsive use, loss of control, craving NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom With chronic use of addictive drugs, neuronal adaptations occur Receptors up- or down-regulate Neurotransmitter levels change Transporters down-regulate Repeated use of drug Chromatin structure changes Altered neurogenesis Dendrite spines increase or decrease NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Chronic nicotine increases acetylcholine (nicotinic) receptors in the brain NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Dopamine receptors are decreased in reward pathway of drug abusers Volkow et al., 2004 NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Amphetamines increase dendritic spines normal Meth Robinson et al., 2001 NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Adaptations occur in disease Addiction Congestive heart failure dopamine decreases norepinephrine increases DA receptors decrease β-receptors decrease dendrites change structure myofibrils change structure chromatin remodels chromatin remodels synapses remodel muscle cells remodel dysfunctional prefrontal cortex dysfunctional ventricle NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Test your knowledge! Can nicotine change your brain? You bet! Which of the following changes occur with repeated use of nicotine? More nicotinic receptors More dendritic spines NSTA Webinar-Understanding the Brain... Altered chromatin structure Altered dopamine release Fewer dopamine receptors RD Schwartz-Bloom Let us Pause Two Minutes for Questions NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Additional Resources for High School Teachers 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 in the Brain (G Gross de Nunez & RD Schwartz-Bloom) NSTA Webinar-Understanding the Brain... www.films.com RD Schwartz-Bloom Additional 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, 17 Adapted from www.rise.duke.edu/resources.html (Understanding FASD) (Illustration by Mark Williams) Synapses: Slides 33-36, 43,45, 48, 49 Adapted from RD Schwartz-Bloom for NIDA. See http://www.drugabuse.gov/pubs/teaching/Teaching4/Teaching.html Acetylcholine Synapses: Slides 37, 38, 46 From GG Gross de Nunez and RD Schwartz-Bloom. Animated Neuroscience & the Actions of Nicotine, Cocaine, & Marijuana in the Brain (www.films.com) NSTA Webinar-Understanding the Brain... RD Schwartz-Bloom Thank you to the sponsor of tonight's Web Seminar: This web seminar contains information about programs, products, and services offered by third parties, as well as links to third-party websites. The presence of a listing or such information does not constitute an endorsement by NSTA of a particular company or organization, or its programs, products, or services. http://learningcenter.nsta.org http://www.elluminate.com National Science Teachers Association Dr. Francis Q. Eberle, Executive Director Zipporah Miller, Associate Executive Director Conferences and Programs Al Byers, Assistant Executive Director e-Learning NSTA Web Seminars Paul Tingler, Director Jeff Layman, Technical Coordinator LIVE INTERACTIVE LEARNING @ YOUR DESKTOP
