title: Amphetamine activates an amine-gated chloride channel to generate behavioral effects in Caenorhabditis elegans.
abstract: Amphetamine is a highly addictive psychostimulant, which is thought to generate its effects by promoting release of dopamine through reverse activation of dopamine transporters. However, some amphetamine-mediated behaviors persist in dopamine transporter knock-out animals, suggesting the existence of alternative amphetamine targets. Here we demonstrate the identification of a novel amphetamine target by showing that in Caenorhabditis elegans, a large fraction of the behavioral effects of amphetamine is mediated through activation of the amine-gated chloride channel, LGC-55. These findings bring to light alternative pathways engaged by amphetamine, and urge rethinking of the molecular mechanisms underlying the effects of this highly-addictive psychostimulant.
authors.affiliation: Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota 58202-9037, USA.
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Safratowich
authors.forename: Chee
authors.initials: C
authors.lastname: Lor
authors.forename: Laura
authors.initials: L
authors.lastname: Bianchi
authors.forename: Lucia
authors.initials: L
authors.lastname: Carvelli
mesh_terms: D000588:Amines / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018118:Chloride Channels / Q000235:genetics / Q000502:physiology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D055786:Gene Knockout Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D017982:Receptors, Biogenic Amine / Q000235:genetics / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: D000588:Amines; D029742:Caenorhabditis elegans Proteins; D000697:Central Nervous System Stimulants; D018118:Chloride Channels; D050483:Dopamine Plasma Membrane Transport Proteins; C542018:LGC-55 protein, c elegans; D017982:Receptors, Biogenic Amine; D012965:Sodium Chloride; D011189:Potassium Chloride; D000661:Amphetamine
keywords: Amphetamine; C. elegans; Dopamine Transporters; Electrophysiology; Ion Channels; Membrane Proteins