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The Journal of Neuroscience, November 26, 2003, 23(34):10859-10866

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Cellular/Molecular
Long-Term K⁺ Channel-Mediated Dampening of Dopamine Neuron Excitability by the Antipsychotic Drug Haloperidol

Junghyun Hahn, Tonia E. Tse, and Edwin S. Levitan

Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261

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.

Key words: dopamine neuron; pacemaker activity; voltage clamp; haloperidol; A-type K⁺ channel; mRNA

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Received July 1, 2003; revised August 5, 2003; accepted August 12, 2003.

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