title: Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity.
abstract: Acid-sensing ion channel 1A (ASIC1A) is abundant in the nucleus accumbens (NAc), a region known for its role in addiction. Because ASIC1A has been suggested to promote associative learning, we hypothesized that disrupting ASIC1A in the NAc would reduce drug-associated learning and memory. However, contrary to this hypothesis, we found that disrupting ASIC1A in the mouse NAc increased cocaine-conditioned place preference, suggesting an unexpected role for ASIC1A in addiction-related behavior. Moreover, overexpressing ASIC1A in rat NAc reduced cocaine self-administration. Investigating the underlying mechanisms, we identified a previously unknown postsynaptic current during neurotransmission that was mediated by ASIC1A and ASIC2 and thus well positioned to regulate synapse structure and function. Consistent with this possibility, disrupting ASIC1A altered dendritic spine density and glutamate receptor function, and increased cocaine-evoked plasticity, which resemble changes previously associated with cocaine-induced behavior. Together, these data suggest that ASIC1A inhibits the plasticity underlying addiction-related behavior and raise the possibility of developing therapies for drug addiction by targeting ASIC-dependent neurotransmission.
authors: 1] Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, USA. [2] Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USA. [3].
authors: Collin J
authors: CJ
authors: Kreple
authors: 1] Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA. [2].
authors: Yuan
authors: Y
authors: Lu
authors: Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA.
authors: Rebecca J
authors: RJ
authors: Taugher
authors: Department of Psychology, University of Iowa, Iowa City, Iowa, USA.
authors: Andrea L
authors: AL
authors: Schwager-Gutman
authors: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.
authors: Jianyang
authors: J
authors: Du
authors: 1] Medical Scientist Training Program, University of Iowa, Iowa City, Iowa, USA. [2] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA.
authors: Madeliene
authors: M
authors: Stump
authors: Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA.
authors: Yimo
authors: Y
authors: Wang
authors: Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA.
authors: Ali
authors: A
authors: Ghobbeh
authors: Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA.
authors: Rong
authors: R
authors: Fan
authors: Department of Psychology, University of Iowa, Iowa City, Iowa, USA.
authors: Caitlin V
authors: CV
authors: Cosme
authors: Department of Neurology, University of Iowa, Iowa City, Iowa, USA.
authors: Levi P
authors: LP
authors: Sowers
authors: 1] Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USA. [2] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. [3] Department of Psychology, University of Iowa, Iowa City, Iowa, USA. [4] Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA. [5] Howard Hughes Medical Institute, Iowa City, Iowa, USA.
authors: Michael J
authors: MJ
authors: Welsh
authors: 1] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. [2] Department of Psychology, University of Iowa, Iowa City, Iowa, USA.
authors: Jason J
authors: JJ
authors: Radley
authors: 1] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. [2] Department of Psychology, University of Iowa, Iowa City, Iowa, USA.
authors: Ryan T
authors: RT
authors: LaLumiere
authors: 1] Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa, USA. [2] Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA. [3] Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, Iowa, USA. [4] Department of Neurosurgery, University of Iowa, Iowa City, Iowa, USA. [5] Department of Veterans Affairs Medical Center, Iowa City, Iowa, USA.
authors: John A
authors: JA
authors: Wemmie
mesh_terms: D062565:Acid Sensing Ion Channels / Q000172:deficiency / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000037:antagonists & inhibitors*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D003042:Cocaine