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.
Keywords:
Amphetamine; C. elegans; Dopamine Transporters; Electrophysiology; Ion Channels; Membrane Proteins.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amines / metabolism
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Amphetamine / pharmacology*
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Animals
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Caenorhabditis elegans / drug effects*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / physiology
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / physiology*
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Central Nervous System Stimulants / pharmacology
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Chloride Channels / genetics
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Chloride Channels / physiology*
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Dopamine Plasma Membrane Transport Proteins / genetics
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Dopamine Plasma Membrane Transport Proteins / physiology
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Dose-Response Relationship, Drug
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Female
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Gene Knockout Techniques
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Ion Channel Gating / drug effects
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Membrane Potentials / drug effects
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Oocytes / metabolism
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Oocytes / physiology
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Patch-Clamp Techniques
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Potassium Chloride / pharmacology
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Receptors, Biogenic Amine / genetics
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Receptors, Biogenic Amine / physiology*
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Sodium Chloride / pharmacology
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Time Factors
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Xenopus laevis
Substances
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Amines
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Caenorhabditis elegans Proteins
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Central Nervous System Stimulants
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Chloride Channels
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Dopamine Plasma Membrane Transport Proteins
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LGC-55 protein, c elegans
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Receptors, Biogenic Amine
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Sodium Chloride
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Potassium Chloride
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Amphetamine