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      Drug Abuse and the Simplest Neurotransmitter

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          Abstract

          Neurotransmitter vesicles are known to concentrate hydrogen ions (or protons), the simplest ion, and to release them during neurotransmission. Furthermore, receptors highly sensitive to protons, acid-sensing ion channels (ASICs), were previously localized on the opposite side of the synaptic cleft on dendritic spines. Now, recent experiments provide some of the strongest support to date that protons function as a neurotransmitter in mice, crossing synapses onto medium spiny neurons of the nucleus accumbens (NAc), activating ASICs, and ultimately suppressing drug abuse-related behaviors.

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          The glutamate homeostasis hypothesis of addiction.

          Peter Kalivas (2009)
          Addiction is associated with neuroplasticity in the corticostriatal brain circuitry that is important for guiding adaptive behaviour. The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use. A failure of the prefrontal cortex to control drug-seeking behaviours can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.
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            The Ctenophore Genome and the Evolutionary Origins of Neural Systems

            Leonid L. Moroz, Kevin Kocot, Mathew Citarella … (2014)
            The origins of neural systems remain unresolved. In contrast to other basal metazoans, ctenophores, or comb jellies, have both complex nervous and mesoderm-derived muscular systems. These holoplanktonic predators also have sophisticated ciliated locomotion, behaviour and distinct development. Here, we present the draft genome of Pleurobrachia bachei, Pacific sea gooseberry, together with ten other ctenophore transcriptomes and show that they are remarkably distinct from other animal genomes in their content of neurogenic, immune and developmental genes. Our integrative analyses place Ctenophora as the earliest lineage within Metazoa. This hypothesis is supported by comparative analysis of multiple gene families, including the apparent absence of HOX genes, canonical microRNA machinery, and reduced immune complement in ctenophores. Although two distinct nervous systems are well-recognized in ctenophores, many bilaterian neuron-specific genes and genes of “classical” neurotransmitter pathways either are absent or, if present, are not expressed in neurons. Our metabolomic and physiological data are consistent with the hypothesis that ctenophore neural systems, and possibly muscle specification, evolved independently from those in other animals.
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              Author and article information

              Journal
              Journal ID (nlm-ta): ACS Chem Neurosci
              Journal ID (iso-abbrev): ACS Chem Neurosci
              Journal ID (publisher-id): cn
              Journal ID (coden): acncdm
              Title: ACS Chemical Neuroscience
              Publisher: American Chemical Society
              ISSN (Print): 1948-7193
              ISSN (Electronic): 1948-7193
              Publication date PMC-release: 23 July 2015
              Publication date (Electronic): 23 July 2014
              Publication date Collection: 17 September 2014
              Volume: 5
              Issue: 9
              Pages: 746-748
              Affiliations
              †Medical Scientist Training Program, ‡Department of Molecular Physiology and Biophysics, §Department of Psychiatry, ∥Interdisciplinary Graduate Program in Neuroscience, ⊥Department of Psychology, and #Department of Neurosurgery, University of Iowa , Iowa City, Iowa 52242, United States
              [▽ ]Department of Veterans Affairs Medical Center , Iowa City, Iowa 52246, United States
              Author notes
              [* ]Mailing address: Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242. Phone: 319-384-3173. Fax: 319-335-7623. E-mail: john-wemmie@ 123456uiowa.edu .
              Article
              DOI: 10.1021/cn500154w
              PMC ID: 4334212
              PubMed ID: 25054738
              SO-VID: ae61389d-b0c1-4e2e-b5db-430b4ce8104d
              Copyright © Copyright © 2014 American Chemical Society
              License:

              This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

              History
              Date received : 16 July 2014
              Funding
              National Institutes of Health, United States
              Categories
              Subject: Viewpoint
              Custom metadata
              document-id-old-9 cn500154w
              document-id-new-14 cn-2014-00154w
              ccc-price

              ScienceOpen disciplines: Neurosciences
              Keywords: asic1a,synaptic transmission,protons,nucleus accumbens,cocaine,addiction
              Data availability:
              ScienceOpen disciplines: Neurosciences
              Keywords: asic1a, synaptic transmission, protons, nucleus accumbens, cocaine, addiction

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