Norepinephrine Transporters Regulate Dopamine

Total Page:16

File Type:pdf, Size:1020Kb

Norepinephrine Transporters Regulate Dopamine B R A I N S T O R M S Clinical Neuroscience Update Neurotransmission of Cognition, Part 1 Dopamine Is a Hitchhiker in Frontal Cortex: Norepinephrine Transporters Regulate Dopamine Stephen M. Stahl, M.D., Ph.D. © Copyright 2003 Physicians Postgraduate Press, Inc. Issue: Since the frontal cortex has a low density of dopamine transporters, dopamine has to be inactivated there by hitching a ride on the norepinephrine transporter of neighboring norepinephrine neurons. PROMISCUOUS TRANSPORTERS take pumps (e.g., fenfluramine and are plentiful on dopaminergic axon One“Ecstasy” personal [3,4-methylenedioxymeth- copy may be printed terminals, thus limiting the diffusion It is well known that the mono- amphetamine; MDMA] by the seroto- of dopamine away from dopamine amine neurotransmitters norepineph- nin transporter; norepinephrine and synapses.3–5 Furthermore, relatively rine, dopamine, and serotonin each dopamine both by the norepinephrine few noradrenergic nerve terminals have their own molecularly distinct transporter).1–4 are present in these same subcortical presynaptic transporters, sometimes This nonselectivity of the trans- brain areas, so the norepinephrine also called “reuptake pumps.”1,2 It is porter comes into play only when transporter has little or no regulatory also common knowledge that most something other than its own neuro- role for dopamine in these places. antidepressants block one or another transmitter shows up in the neigh- On the other hand, dopamine neu- of these transporters and that the pat- borhood. We used to think that rotransmission in the frontal cortex is tern of selectivity of antidepressants this promiscuous selectivity happened far different, because there are very results in their clinical effects (e.g., only when certain drugs capable of few dopamine transporters present serotonin selective vs. norepinephrine interacting with the transporters were in frontal cortex.3–5 This allows dopa- selective vs. dual serotonin and nor- administered or when pathologic cir- mine to diffuse away from the dopa- epinephrine actions).2 What is less cumstances were present, but we mine synapse after it is released, widely appreciated is the fact that the are now learning that it happens where it is free to affect any dopamine transporters themselves are promiscu- normally in frontal cortex to enhance receptor it can reach. The process of ous and not all that selective.3,4 Thus, the geographic scope of dopamine distant, nonsynaptic neurotransmis- numerous drugs and neurotransmit- neurotransmission there as well as sion is sometimes called “volume ters can be transported by these reup- dopamine’s ability to regulate cogni- neurotransmission.”2 This ability of tive functioning.1,3,4 dopamine to navigate over wide areas of frontal cortex may be linked to its BRAINSTORMS is a monthly section of The Journal of Clinical Psychiatry aimed at NEUROTRANSMISSION hypothesized key regulatory role in providing updates of novel concepts emerging DIFFERS FOR SUBCORTICAL cognitive functions, such as working from the neurosciences that have relevance to VERSUS CORTICAL DOPAMINE 2,5 the practicing psychiatrist. memory and attention. From the Neuroscience Education Institute Dopamine inactivation in frontal in Carlsbad, Calif., and the Department of Neurotransmission of dopamine in cortex thus does not depend on do- Psychiatry at the University of California San Diego. subcortical regions such as the basal pamine reuptake; rather, it depends Reprint requests to: Stephen M. Stahl, M.D., ganglia and limbic areas (e.g., nucleus on diffusion, metabolism by the Ph.D., Editor, BRAINSTORMS, Neuroscience Education Institute, 5857 Owens Street, Ste. 102, accumbens) is synaptic, because in enzyme COMT (catechol-O-methyl Carlsbad, CA 92009. these places, dopamine transporters transferase),5 and reaching noradren- 4 J Clin Psychiatry 64:1, January 2003 B R A I N S T O R M S Clinical Neuroscience Update Take-Home Points ◆ Neurotransmission of dopamine in subcortical regions is synaptic, because dopamine transporters © Copyrightare plentiful2003 on Physicians dopaminergic axon Postgraduate terminals there. Press, Inc. ergic nerve terminals that ◆ By contrast, neurotransmission of dopamine in epinephrine in frontal transport dopamine into frontal cortex is both synaptic and nonsynaptic, cortex demonstrate that the norepinephrine neu- because dopamine transporters are not plentiful the transporter for do- 1,3,4 pamine does not regulate rons. The norepineph- there. rine transporter, in fact, dopamine activity, but has even higher affinity ◆ Consequently, after being released from dopamine the transporter for nor- for dopamine than it does synapses in frontal cortex, dopamine diffuses away epinephrine does. Ex- for norepinephrine. This from the synapse to neighboring norepinephrine ploiting these actions with currently available arrangement makes it pos- neurons, which inactivate dopamine by transporting sible for dopamine to dif- drugs can lead to en- it into their presynaptic terminals. fuse over a much wider One personal copy may be printed hancing dopamine, nor- area than its own synapse, epinephrine, or both in and thus affect a much frontal cortex, which greater area of frontal cor- could have therapeutic tex than basal ganglia or nucleus by norepinephrine neurons will actions on cognition in a variety accumbens, for example. change how we use agents that of disorders including depression, act on neurotransmitter transporters. schizophrenia, and attention-deficit/ TWO FOR THE PRICE OF ONE We now know that transporter- hyperactivity disorder.4 ◆ selective reuptake inhibitors are not It is now clear that noradrenergic necessarily transmitter-selective re- neurons play a key regulatory role uptake inhibitors.3 How does this over dopaminergic function in frontal translate into practical psychopharma- REFERENCES cortex, and by extension, over do- cology? For example, if we want to pamine’s ability to regulate cognition. increase dopamine in frontal cortex 1. Gainetdinov RR, Sotnikova TD, Caron MG, Monoamine transporter pharmacology and Not only does dopamine hitch a ride therapeutically, we won’t give a se- mutant mice. Trends Pharmacol Sci on the norepinephrine reuptake pump, lective dopamine reuptake inhibitor 2002;23:367–373 it gets co-stored in synaptic vesicles because there are no dopamine trans- 2. Stahl SM. Essential Psychopharmacology. 2nd ed. New York, NY: Cambridge University with norepinephrine in noradrenergic porters there. We can give a dopa- Press; 2000 neurons. Because of this, both dopa- mine-releasing stimulant, but this 3. Moron JA, Brockington A, Wise RA, et al. mine and norepinephrine get released would also enhance dopamine release Dopamine uptake through the norepinephrine transporter in brain regions with low levels when frontal cortex noradrenergic in subcortical areas, which may not of the dopamine transporter: evidence from nerves fire: 2 neurotransmitters for be desired. Or, we can give something knock-out mouse lines. J Neurosci 2002;22: the price of 1 under physiologic con- that blocks the norepinephrine reup- 389–395 4. Bymaster FP, Katner JS, Nelson DL, et al. ditions in this region of the brain. take pump and increase both dopa- Atomoxetine increases extracellular levels of mine and norepinephrine in cortex, norepinephrine and dopamine in prefrontal TRANSPORTER-SELECTIVE but only norepinephrine in subcortical cortex of rat: a potential mechanism for effi- cacy in attention deficit/hyperactivity disorder. DRUGS ARE NOT NECESSARILY areas, which may be a more favorable Neuropsychopharmacology 2002;27:699–711 TRANSMITTER SELECTIVE portfolio of actions when treating 5. Egan MF, Godberg TE, Kolachana BS, et al. cognitive symptoms.4 Effects of COMT Val 108/158 Met genotype on frontal lobe function and risk for schizo- These new discoveries on the In summary, new insights into phrenia. Proc Natl Acad Sci U S A 2001;98: regulation of frontal cortex dopamine the regulation of dopamine and nor- 6917–6922 J Clin Psychiatry 64:1, January 2003 5.
Recommended publications
  • Molecular Biology of Neuronal Voltage-Gated Calcium Channels
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 30, No 3, 123-130, September 1998 Molecular biology of neuronal voltage-gated calcium channels Hemin Chin and is capable of directing expression of calcium channel activity in heterologous expression systems. In the central Genetics Research Branch, Division of Basic and Clinical Neuroscience Research, nervous system (CNS), VGCCs are expressed by five National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, distinct a1 subunit genes (α1A, α1B, α1C, α1D and α1E), U.S.A. which exhibit further variations due to alternative splicing of the primary RNA transcripts. The α1C and, α1D su b u n i t Accepted 3 August 1998 genes encode dihydropyridine (DHP)-sensitive L-type channels, while the three other α1 subunit genes (α1A, α1B and α1E) give rise to DHP-insensitive P/Q-, N- and R-type channels, respectively. The α2 and δ s u b u n i t proteins are produced by proteolytic cleavage of a larger precursor produced by the single α2-δ gene (Table 1). Introduction Three alternatively spliced variants of the α2 subunit are expressed in a tissue-specific manner. Two variants Calcium ions are important intracellular messengers have been isolated from the brain and skeletal muscle mediating a number of neuronal functions including neuro- (Kim et al., 1992; Williams et al., 1992), and a distinct transmitter release, neurosecretion, neuronal excitation, third splice variant which is expressed in glial cells has survival of eurons, and regulation of gene expression. been recently identified (Puro et al., 1996). In addition to The entry of calcium across the plasmamembrane in the gene encoding the skeletal muscle β subunit, three response to membrane depolarization or activation of 1 other β subunit genes (β2, β3 and β4) have been isolated neurotransmitter receptors represents a major pathway thus far.
    [Show full text]
  • Chemical Neurotransmission
    Cambridge University Press 978-1-107-02598-1 — Stahl's Essential Psychopharmacology 4th Edition Excerpt More Information Chapter1 Chemical neurotransmission Anatomical versus chemical basis of Beyond the second messenger to a neurotransmission 1 phosphoprotein cascade triggering gene 16 Principles of chemical neurotransmission 5 expression Neurotransmitters 5 How neurotransmission triggers gene 18 Neurotransmission: classic, retrograde, expression 18 and volume 6 Molecular mechanism of gene expression Excitation–secretion coupling 8 Epigenetics 24 Signal transduction cascades 9 What are the molecular mechanisms 24 Overview 9 of epigenetics? Forming a second messenger 11 How epigenetics maintains or changes the status quo 26 Beyond the second messenger to phosphoprotein messengers 13 Summary 26 Modern psychopharmacology is largely the story of neurons, not unlike millions of telephone wires chemical neurotransmission. To understand the actions within thousands upon thousands of cables. The ana- of drugs on the brain, to grasp the impact of diseases tomically addressed brain is thus a complex wiring upon the central nervous system, and to interpret the diagram, ferrying electrical impulses to wherever behavioral consequences of psychiatric medicines, the “wire” is plugged in (i.e., at a synapse). Synapses one must be fluent in the language and principles of canformonmanypartsofaneuron,notjustthe chemical neurotransmission. The importance of this dendrites as axodendritic synapses, but also on the fact cannot be overstated for the student of psychophar- soma as axosomatic synapses, and even at the begin- macology. This chapter forms the foundation for the ning and at the end of axons (axoaxonic synapses) entire book, and the roadmap for one’s journey through (Figure 1-2).
    [Show full text]
  • Part III: Modeling Neurotransmission – a Cholinergic Synapse
    Part III: Modeling Neurotransmission – A Cholinergic Synapse Operation of the nervous system is dependent on the flow of information through chains of neurons functionally connected by synapses. The neuron conducting impulses toward the synapse is the presynaptic neuron, and the neuron transmitting the signal away from the synapse is the postsynaptic neuron. Chemical synapses are specialized for release and reception of chemical neurotransmitters. For the most part, neurotransmitter receptors in the membrane of the postsynaptic cell are either 1.) channel-linked receptors, which mediate fast synaptic transmission, or 2.) G protein-linked receptors, which oversee slow synaptic responses. Channel-linked receptors are ligand-gated ion channels that interact directly with a neurotransmitter and are called ionotropic receptors. Alternatively, metabotropic receptors do not have a channel that opens or closes but rather, are linked to a G-protein. Once the neurotransmitter binds to the metabotropic receptor, the receptor activates the G-protein which, in turn, goes on to activate another molecule. 3a. Model the ionotropic cholinergic synapse shown below. Be sure to label all of the following: voltage-gated sodium channel, voltage-gated potassium channel, neurotransmitter, synaptic vesicle, presynaptic cell, postsynaptic cell, potassium leak channel, sodium-potassium pump, synaptic cleft, acetylcholine receptor, acetylcholinesterase, calcium channel. When a nerve impulse (action potential) reaches the axon terminal, it sets into motion a chain of events that triggers the release of neurotransmitter. You will next model the events of neurotransmission at a cholinergic synapse. Cholinergic synapses utilize acetylcholine as the chemical of neurotransmission. MSOE Center for BioMolecular Modeling Synapse Kit: Section 3-6 | 1 Step 1 - Action potential arrives at the Step 2 - Calcium channels open in the terminal end of the presynaptic cell.
    [Show full text]
  • Regulation of Neuronal Communication by G Protein-Coupled Receptors ⇑ Yunhong Huang, Amantha Thathiah
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector FEBS Letters 589 (2015) 1607–1619 journal homepage: www.FEBSLetters.org Review Regulation of neuronal communication by G protein-coupled receptors ⇑ Yunhong Huang, Amantha Thathiah VIB Center for the Biology of Disease, Leuven, Belgium Center for Human Genetics (CME) and Leuven Institute for Neurodegenerative Diseases (LIND), University of Leuven (KUL), Leuven, Belgium article info abstract Article history: Neuronal communication plays an essential role in the propagation of information in the brain and Received 31 March 2015 requires a precisely orchestrated connectivity between neurons. Synaptic transmission is the mech- Revised 5 May 2015 anism through which neurons communicate with each other. It is a strictly regulated process which Accepted 5 May 2015 involves membrane depolarization, the cellular exocytosis machinery, neurotransmitter release Available online 14 May 2015 from synaptic vesicles into the synaptic cleft, and the interaction between ion channels, G Edited by Wilhelm Just protein-coupled receptors (GPCRs), and downstream effector molecules. The focus of this review is to explore the role of GPCRs and G protein-signaling in neurotransmission, to highlight the func- tion of GPCRs, which are localized in both presynaptic and postsynaptic membrane terminals, in reg- Keywords: G protein-coupled receptors ulation of intrasynaptic and intersynaptic communication, and to discuss the involvement of G-proteins astrocytic GPCRs in the regulation of neuronal communication. Neuronal communication Ó 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Synaptic transmission Signaling Astrocytes Neurons Autoreceptors Neurotransmitters 1.
    [Show full text]
  • RIM-BP2 Primes Synaptic Vesicles Via Recruitment of Munc13-1 At
    RESEARCH ARTICLE RIM-BP2 primes synaptic vesicles via recruitment of Munc13-1 at hippocampal mossy fiber synapses Marisa M Brockmann1†, Marta Maglione2,3,4†, Claudia G Willmes5†, Alexander Stumpf6, Boris A Bouazza1, Laura M Velasquez6, M Katharina Grauel1, Prateep Beed6, Martin Lehmann3, Niclas Gimber6, Jan Schmoranzer4, Stephan J Sigrist2,4,5*, Christian Rosenmund1,4*, Dietmar Schmitz4,5,6* 1Institut fu¨ r Neurophysiologie, Charite´ – Universita¨ tsmedizin Berlin, corporate member of Freie Universita¨ t Berlin, Humboldt-Universita¨ t zu Berlin, and Berlin Institute of Health, Berlin, Germany; 2Freie Universita¨ t Berlin, Institut fu¨ r Biologie, Berlin, Germany; 3Leibniz-Forschungsinstitut fu¨ r Molekulare Pharmakologie (FMP), Berlin, Germany; 4NeuroCure Cluster of Excellence, Berlin, Germany; 5DZNE, German Center for Neurodegenerative Diseases, Berlin, Germany; 6Neuroscience Research Center, Charite´ – Universita¨ tsmedizin Berlin, corporate member of Freie Universita¨ t Berlin, Humboldt-Universita¨ t zu Berlin, and Berlin Institute of Health, Berlin, Germany Abstract All synapses require fusion-competent vesicles and coordinated Ca2+-secretion coupling for neurotransmission, yet functional and anatomical properties are diverse across *For correspondence: different synapse types. We show that the presynaptic protein RIM-BP2 has diversified functions in [email protected] (SJS); neurotransmitter release at different central murine synapses and thus contributes to synaptic [email protected] diversity. At hippocampal pyramidal CA3-CA1 synapses, RIM-BP2 loss has a mild effect on (CR); neurotransmitter release, by only regulating Ca2+-secretion coupling. However, at hippocampal [email protected] (DS) mossy fiber synapses, RIM-BP2 has a substantial impact on neurotransmitter release by promoting †These authors contributed vesicle docking/priming and vesicular release probability via stabilization of Munc13-1 at the active equally to this work zone.
    [Show full text]
  • G-Protein-Coupled Receptors in CNS: a Potential Therapeutic Target for Intervention in Neurodegenerative Disorders and Associated Cognitive Deficits
    cells Review G-Protein-Coupled Receptors in CNS: A Potential Therapeutic Target for Intervention in Neurodegenerative Disorders and Associated Cognitive Deficits Shofiul Azam 1 , Md. Ezazul Haque 1, Md. Jakaria 1,2 , Song-Hee Jo 1, In-Su Kim 3,* and Dong-Kug Choi 1,3,* 1 Department of Applied Life Science & Integrated Bioscience, Graduate School, Konkuk University, Chungju 27478, Korea; shofi[email protected] (S.A.); [email protected] (M.E.H.); md.jakaria@florey.edu.au (M.J.); [email protected] (S.-H.J.) 2 The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC 3010, Australia 3 Department of Integrated Bioscience & Biotechnology, College of Biomedical and Health Science, and Research Institute of Inflammatory Disease (RID), Konkuk University, Chungju 27478, Korea * Correspondence: [email protected] (I.-S.K.); [email protected] (D.-K.C.); Tel.: +82-010-3876-4773 (I.-S.K.); +82-43-840-3610 (D.-K.C.); Fax: +82-43-840-3872 (D.-K.C.) Received: 16 January 2020; Accepted: 18 February 2020; Published: 23 February 2020 Abstract: Neurodegenerative diseases are a large group of neurological disorders with diverse etiological and pathological phenomena. However, current therapeutics rely mostly on symptomatic relief while failing to target the underlying disease pathobiology. G-protein-coupled receptors (GPCRs) are one of the most frequently targeted receptors for developing novel therapeutics for central nervous system (CNS) disorders. Many currently available antipsychotic therapeutics also act as either antagonists or agonists of different GPCRs. Therefore, GPCR-based drug development is spreading widely to regulate neurodegeneration and associated cognitive deficits through the modulation of canonical and noncanonical signals.
    [Show full text]
  • The Mechanisms and Functions of Spontaneous Neurotransmitter Release
    REVIEWS The mechanisms and functions of spontaneous neurotransmitter release Ege T. Kavalali Abstract | Fast synaptic communication in the brain requires synchronous vesicle fusion that is evoked by action potential-induced Ca2+ influx. However, synaptic terminals also release neurotransmitters by spontaneous vesicle fusion, which is independent of presynaptic action potentials. A functional role for spontaneous neurotransmitter release events in the regulation of synaptic plasticity and homeostasis, as well as the regulation of certain behaviours, has been reported. In addition, there is evidence that the presynaptic mechanisms underlying spontaneous release of neurotransmitters and their postsynaptic targets are segregated from those of evoked neurotransmission. These findings challenge current assumptions about neuronal signalling and neurotransmission, as they indicate that spontaneous neurotransmission has an autonomous role in interneuronal communication that is distinct from that of evoked release. 10–13 Docked vesicles Our current insights into the mechanisms under­lying relatively intact . Thus, although these experiments Synaptic vesicles that are synaptic transmission originate from experiments that proved the vesicular hypothesis of neurotransmitter tethered to the presynaptic were conducted in the 1950s by Bernard Katz and col- release, they raised the question of whether spontane- membrane or the active zone leagues1–3 (FIG. 1). A key aspect of these studies was the ous release events originate from the same vesicular traf- structure. According to current discovery of spontaneous neurotransmitter release ficking pathway as evoked neurotransmission14. Recent views, not all docked vesicles are fully primed for fusion and events, which seemed to occur in discrete ‘quantal’ advances in our understanding support the autonomous release of neurotransmitter. packets (FIG.
    [Show full text]
  • Long-Term Dopamine Neurochemical Monitoring in Primates
    Long-term dopamine neurochemical monitoring in primates Helen N. Schwerdta,b,c, Hideki Shimazua,b, Ken-ichi Amemoria,b, Satoko Amemoria,b, Patrick L. Tierneya,b, Daniel J. Gibsona,b, Simon Honga,b, Tomoko Yoshidaa,b, Robert Langerc,d, Michael J. Cimac,e, and Ann M. Graybiela,b,1 aMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139; bDepartment of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; cKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139; dDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; and eDepartment of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 Contributed by Ann M. Graybiel, November 1, 2017 (sent for review August 4, 2017; reviewed by Richard Courtemanche, Paul W. Glimcher, and Christopher I. Moore) Many debilitating neuropsychiatric and neurodegenerative disor- acute dopamine measurements (5–8), with stable measurements ders are characterized by dopamine neurotransmitter dysregula- only for a few hours. The lack of chronic chemical sensors exists tion. Monitoring subsecond dopamine release accurately and for despite great progress in the chronic electrophysiological re- extended, clinically relevant timescales is a critical unmet need. cording of spike and local field potential activity in behaving Especially valuable has been the development of electrochemical nonhuman primates. Chronic measurements of dopamine will fast-scan cyclic voltammetry implementing microsized carbon fiber aid in the identification of dopamine’s contribution to complex probe implants to record fast millisecond changes in dopamine behaviors degraded in human disorders, and to aid in testing the concentrations. Nevertheless, these well-established methods have clinical feasibility of treatments.
    [Show full text]
  • The Mitochondrion
    The mitochondrion: the powerhouse behind Professor Elizabeth Jonas neurotransmission ‘We think we have found a key molecule that forms a major cell death-inducing mitochondrial ion channel’ THE MITOCHONDRION: THE POWERHOUSE BEHIND NEUROTRANSMISSION Professor Elizabeth Jonas and her colleagues at Yale University study the function of cell components called Ca2+ Ca2+ Ca2+ mitochondria and their role in neurotransmission. In particular, Professor Jonas is interested in characterising how 3. Calcium is released from mitochondria. 2. Repeated action potentials (tetanus) invade When another action potential invades 1. An1. action An action potential potential invades inv adesthe terminal. the 2. Repeated action potentials 3. Calcium is released from channels in the mitochondrial membrane affect neuronal function during processes like memory formation and terminal. the terminal, the increased calcium levels Someterminal. vesicles fuse, releasing (tetanus) invade terminal. mitochondria. learning, and how they enhance or reduce neuronal viability during disease. Many vesicles fuse. from mitochondrial release plus plasma neurotransmitter.Some vesicles fuse, releasing Many vesicles fuse. When another action potential neurotransmitter. CalciumCalcium is ta isk takenen up up into into mitochondria. invadesmembrane the terminal, Ca2+ influx increase vesicle mitochondria. the fusion,increased potentiating calcium levelsneurotransmission. from mitochondrial release plus plasma membrane Ca2+ influx Neurotransmission – firing on all can have profound effects on neuronal but they participate in carefully regulating increase vesicle fusion, cylinders. function and viability, and implications in calcium levels during neurotransmission. and calcium dynamics of neurotransmission the mitochondrial permeability transition potentiatingand its classical neurotr roleansmission. is to prevent other disease. This process also has important effects on and on studying how these interact, like pore.
    [Show full text]
  • BIO 337 NEUROTRANSMISSION & NEUROMODULATION Class Meets
    BIO 337 NEUROTRANSMISSION & NEUROMODULATION Class meets on Mondays and Fridays from 1:00 to 2:20 p.m. in Melville Library W4550 Instructors: Dr. Arianna Maffei (course director), Dr. Lonnie Wollmuth Guest Instructors: Dr. Lorna Role, Dr. Alfredo Fontanini, Dr. David Talmage Department of Neurobiology and Behavior TA: Kelvin Chan, Graduate Program in Neuroscience, Department of Neurobiology and Behavior uTA: Timur Mukhammadov, Undergraduate Biology, Neuroscience Specialization Readings: Introduction to Neuropsychopharmacology by Leslie L. Iversen, Susan D. Iversen, Floyd E. Bloom, Robert H. Roth, Oxford University Press CLASS SCHEDULE Date Instructor Topic 1. Monday 01/22 Wollmuth Introduction 2. Friday 01/26 Wollmuth Membrane excitability 3. Monday 01/29 Wollmuth Cell-to-cell signaling 4. Friday 02/02 Wollmuth Amino acid transmitters 5. Monday 02/05 Wollmuth Local networks 6. Friday 02/09 Wollmuth Dysfunction of excitability: Epilepsy 7. Monday 02/12 Wollmuth Slow synaptic modulation 8. Friday 02/16 Wollmuth Catecholamines 9. Monday 02/19 Wollmuth Synaptic plasticity Friday 02/23 Exam 1 (Lectures 1-9, Wollmuth and Maffei) 10. Monday 02/26 Wollmuth Parkinson’s Disease 11. Friday 03/02 Wollmuth The neurobiology of addictive behaviors 12. Monday 03/05 Maffei Stimulants and the brain 13. Friday 03/09 Maffei Mood regulators Spring Break 14. Monday 03/19 Maffei Affective disorders 15. Friday 03/23 Maffei Opioids 16. Monday 03/26 Role The most versatile of neurotransmitters: Acetylcholine 17. Friday 03/30 Maffei Other neuronal signals 18. Monday 04/02 Maffei How do we study brain, behavior and reward? Friday 04/06 Exam 2 (Lectures 10-18, Wollmuth and Maffei) 19.
    [Show full text]
  • Neurotransmission Fact Sheet
    Neurotransmission Fact Sheet The brain and nervous system are made of billions of nerve cells, called neurons. Neurons have three main parts: cell body, dendrites, and axon. The axon is covered by the myelin sheath. Cell Body is in charge of the neuron’s Dendrites receive messages activities. from other neurons. Myelin Sheath covers the axon to protect it and help messages travel faster and easier. Axon sends messages from the cell body to the dendrites of other neurons. The transfer of information between neurons is called neurotransmission. This is how neurotransmission works: 1. A message travels from the dendrites through the cell body and to the end of the axon. 2. The message causes the chemicals, called neurotransmitters, to be released from the end of the axon into the synapse. The neurotransmitters carry the message with them into the synapse. The synapse is the space between the axon of one neuron and the dendrites of another neuron. 3. The neurotransmitters then travel across the synapse to special places on the dendrites of the next neuron, called receptors. The neurotransmitters fit into the receptors like keys in locks. 4. Once the neurotransmitter has attached to the receptors of the second neuron, the message is passed on. 5. The neurotransmitters are released from the receptors and are either broken down or go back into the axon of the first neuron. Teacher copy: Module 1 Neurotransmission Fact Sheet The brain and nervous system are made of billions of nerve cells, called neurons. Neurons have three main parts: cell body, dendrites, and axon.
    [Show full text]
  • The Relationship Between Psychoactive Drugs, the Brain and Psychosis Sutapa Basu1*And Deeptanshu Basu2
    Basu and Basu. Int Arch Addict Res Med 2015, 1:1 ISSN: 2474-3631 International Archives of Addiction Research and Medicine Review Article: Open Access The Relationship between Psychoactive Drugs, the Brain and Psychosis Sutapa Basu1*and Deeptanshu Basu2 1Institute of Mental Health, Singapore 2University at Buffalo, State University of New York, USA *Corresponding author: Sutapa Basu, Consultant, Institute of Mental Health, Singapore, Tel: +6597112015, E-mail: [email protected] grey of the midbrain [7] whereas some alter neurotransmission Abstract by interacting with molecular components of the sending and This paper explores the interaction between four psychoactive drugs, receiving process, an example being cocaine. Some drugs alter namely MDMA (Ecstasy), Cocaine, Methamphetamine and LSD, neurotransmission in different fashion. Benzodiazepines enhance the with neurotransmitters in the brain with the aim of understanding response of receiving cells mediated by serotonin, possibly with the what links exist between these drugs and Psychosis. The paper is restricted to three neurotransmitters – dopamine, serotonin, and involvement of GABA [8]. One of the unwanted effects of many of the norepinephrine (noradrenaline) and explores in some detail how psychoactive drugs is psychotic symptoms. However, most research they are affected by the aforementioned drugs. The paper aims has been centered on cannabis (Marijuana) use and Psychosis. This to go beyond existing research on drugs and psychosis which has paper therefore explores to what extent other psychoactive drugs been primarily limited to cannabis (Marijuana) and psychosis. The affect psychotic symptoms and illnesses. findings and conclusions drawn show that all the drugs explored have the potential to induce psychosis in abusers to some degree; In order to delve into the above topic, secondary research from the effects vary from drug to drug.
    [Show full text]