Abstract
Antipsychotic drugs require days of treatment to begin to produce therapeutic effects. We report that in vivo treatment with the antipsychotic drug haloperidol acts with a delay of days to slow spontaneous repetitive firing by isolated midbrain dopamine neurons. The decreased excitability is caused by an increased number of functional A-type K+ channels without any change in gating properties. Upregulation of dopamine neuron Kv4.3 mRNA accounts for this effect, demonstrating a role for channel gene expression in this delayed drug action. The resultant long-term dampening of dopamine neuron excitability may serve to tone down the dopamine system.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Animals
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Antipsychotic Agents / pharmacology*
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Cell Separation
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Dopamine / biosynthesis*
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Enzyme Inhibitors / pharmacology
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Haloperidol / pharmacology*
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Mesencephalon / cytology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Patch-Clamp Techniques
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Polymerase Chain Reaction
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Potassium / metabolism
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Potassium Channel Blockers / pharmacology
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Potassium Channels / metabolism*
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Rats
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Rats, Sprague-Dawley
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Tetraethylammonium / pharmacology
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Time
Substances
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Antipsychotic Agents
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Enzyme Inhibitors
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Potassium Channel Blockers
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Potassium Channels
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Tetraethylammonium
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Mitogen-Activated Protein Kinases
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Haloperidol
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Potassium
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Dopamine