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Activity Intrinsic Vol. (Suppl. ) Intrinsic 201 Activity www.IntrinsicActivity.org Published by th ISSN 2309-8503 Austrian Pharmacological Society Dopamine 2016 Vienna, 5–8 September 2016 MAEETING BSTRACTS Intrinsic Activity is an online, open-access publication medium published by the Austrian Pharmacological Society (APHAR). The Journal welcomes contributions in the fields of Pharmacology, Pharmacotherapy and other fields in biomedicine. Contributions may be of type meeting abstracts, research articles, position papers, commentaries or similar. For submission instructions and all other information regarding publication in the journal visit: www.IntrinsicActivity.org Correspondence Intrinsic Activity c/o Institute for Experimental and Clinical Pharmacology Medical University of Graz Universitätsplatz 4 8010 Graz, Austria Tel.: +43 (316) 380-4305 Fax: +43 (316) 380-9645 E-mail: [email protected] Website: www.IntrinsicActivity.org ISSN: 2309-8503 Austrian Pharmacological Society c/o Institute of Pharmacology Centre for Physiology and Pharmacology Medical University of Vienna Währinger Straße 13a 1090 Wien, Austria E-mail: [email protected] Copyright, open access and permission to use Articles are published under a Creative Commons license (Creative Commons, attribution, non-commercial), that allows reuse subject only to the use being non-commercial and the article being fully attributed. The Publisher and Austrian Pharmacological Society retain the license that allows publishing of the articles in Intrinsic Activity, any derivative product or any other Intrinsic Activity product (present or future) and allows sub-licensing such rights and exploit all subsidiary rights. Authors retain the license to use their articles for their own non-commercial purposes, specifically: Posting a pdf of their own article on their own personal or institutional website for which no charge for access is made. Making a reasonable number of copies for personal or non-commercial professional use. This includes the contributors’ own teaching activities. Republishing part or all of the article in a book or publication edited by the author (except for multiple publications in the same book or publication). Using individual figures or tables in other publications published by a third party. Extracts of text other than individual phrases or sentences may also be used provided that these are identified as quotations along with giving the appropriate reference to the original publication. Using the article in a course pack or compilation (whether paper or electronic) in the author’s instithution. This does not apply if a commercial charge is made for the compilation or course. Third parties (other than the Publisher, Austrian Pharmacological Society, or authors) may download, print or store articles published in the journal for their private or professihonal, non-commercial use. The use of articles published in the journal, or any artwork contained therein, for educational, non-commercial purposes is granted provided that the appropriate reference to the journal and original article is given. Any commercial use of articles published in Intrinsic Activity requires the permission of the Publisher. Disclaimer The Publisher, the Austrian Pharmacological Society and Editor(s) cannot be held responsible for errors or any consequences arising from the use of information contained in this journal. The views and opinions expressed do not necessarily reflect those of the Publisher, Austrian Pharmacological Society or Editor(s). Neither does the publication of advertisements constitute any The background image for the meeting banner was kindly provided by endorsement by the Publisher, Austrian Pharmacological Society or Editor(s) © WienTourismus / Christian Stemper of the products advertised. © 2016 Intrinsic Activity, ISSN 2309-8503; Austrian Pharmacological Society (APHAR) Intrinsic Activity, 2016; 4 (Suppl. 2) http://www.intrinsicactivity.org/2016/4/S2 published online: 29 August 2016 Dopamine 2016 Vienna, 5 – 8 September 2016 Plenary Lectures & Oleh Hornykiewicz Symposium combined lines of evidence suggest that DA dysfunction may be an early event leading to additional consequences on the rest of the circuitry and behavior. We will review the evidence critically and A1.1 develop a model as well as future directions to move this under- Dopamine in schizophrenia: where does it stand in the cascade standing further. of pathological events? References Anissa ABI-DARGHAM* 1. Weinstein JJ, Chohan MO, Slifstein M, Kegeles LS, Moore H, Abi- Department of Psychiatry, Columbia University, New York, NY, Dargham A: Pathway-specific dopamine abnormalities in United States of America schizophrenia. Biol Psychiatry, 2016; in press. *E-mail: [email protected] doi:10.1016/j.biopsych.2016.03.2104 Intrinsic Activity, 2016; 4(Suppl. 2): A1.1 2. Slifstein M, van de Giessen E, Van Snellenberg J, Thompson JL, http://www.intrinsicactivity.org/2016/4/S2/A1.1 Narendran R, Gil R, Hackett E, Girgis R, Ojeil N, Moore H, D’Souza D, The dopamine (DA) dysfunction in schizophrenia has recently moved Malison RT, Huang Y, Lim K, Nabulsi N, Carson RE, Lieberman JA, from being a hypothesis based on clinical observations, to a stage of Abi-Dargham A: Deficits in prefrontal cortical and extrastriatal refined and topographically precise sets of alterations documented dopamine release in schizophrenia: a positron emission across multiple labs with positron emission tomography (PET) tomographic functional magnetic resonance imaging study. imaging studies, that showed excess striatal dopamine synthesis, JAMA Psychiatry, 2015; 72(4):316–324. doi:10.1001/jamapsychiatry.2014.2414 release, and D2 supersensitivity [1]. Recent data suggest also profound extrastriatal deficits in DA release [2]. The presence of 3. Kellendonk C, Simpson EH, Kandel ER: Modeling cognitive opposing findings of striatal excess and extrastriatal deficit including endophenotypes of schizophrenia in mice. Trends Neurosci, 2009; midbrain deficit is puzzling as it suggests that striatal excess may not 32(6):347–358. doi:10.1016/j.tins.2009.02.003 be a consequence of midbrain DA cells overactivity. A mechanistic 4. Schizophrenia Working Group of the Psychiatric Genomics understanding of the DA dysfunction is missing. Animal models may Consortium: Biological insights from 108 schizophrenia-associated shed some light on the pathogenic mechanisms involved. In genetic loci. Nature, 2014; 511(7510):421–427. doi:10.1038/nature13595 particular, the D2 overexpressing (D2OE) [3] mouse has shown that cortical-dependent cognitive deficit and abnormal cortical DA signaling can be a consequence of developmental abnormalities in striatal D2 stimulation. Since many developmental factors, both Edited by: Thomas Griesbacher (Austrian Pharmacological Society APHAR, genetic [4] and environmental, have been shown to be at play in and Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Austria; [email protected]) schizophrenia, and shown to affect dopaminergic indices, these © 2016 Intrinsic Activity, ISSN 2309-8503; Austrian Pharmacological Society (APHAR) page 1 of 84 (not for citation purpose) Intrinsic Activity, 2016; 4 (Suppl. 2) Dopamine 2016 A1.2 studies have shown that dopamine transients are an important Allosteric mechanisms of the dopamine signaling machines: component of monoamine transmission. New properties of transients The moving stories of GPCRs and transporters are still being described, such as previously unappreciated cross- Harel WEINSTEIN*, George KHELASHVILI, Michael V. LEVINE and hemispheric dopamine signaling. Remarkably, we find that a majority Michel CUENDET of dopamine transients are synchronous between hemispheres, Physiology and Biophysics, Weill Cornell Medical College, Cornell concurring with the physiological synchrony that is observed in many University, New York, NY, United States of America parts of the brain.To explore the specific actions of dopamine at its *E-mail: [email protected] receptors we developed a method to chemotype dopamine receptors Intrinsic Activity, 2016; 4(Suppl. 2): A1.2 in situ. We use a modified form of iontophoresis enabling controlled http://www.intrinsicactivity.org/2016/4/S2/A1.2 delivery of dopamine receptor agonists and antagonists locally to the site of the recording electrode. We monitor their effects at dopamine The molecular machines that enable dopamine (DA) signaling belong autoreceptors by examining how they alter dopamine release. By to the large category of allosteric proteins that perform complex pairing electrochemical measurements with electrophysiology, we functions triggered and / or enabled by the binding of the neurotrans- can also monitor effects on postsynaptic receptors and cell-firing mitter in binding sites located distally from the intracellular regions of without disturbing animal behavior. These methods are sufficiently the proteins. The mechanisms of these “actions at a distance” are of quantitative to generate dose response curves in multiple dopamine- great interest not only because of the essential role of dopaminergic rich microenvironments. Chemotyping enables real-time observa- signaling in normal physiology and in disease, but also because the tions of dopamine interacting with different receptor subtypes to current assays of dopaminergic function, and the need to intervene mediate animal behavior. New tools also enable us to explore mechanistically and therapeutically can no longer ignore the role of unexpected
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