Long-term K+ Channel-Mediated Dampening of Dopamine Neuron Excitability by the Antipsychotic Drug Haloperidol

J Neurosci. 2003 Nov 26;23(34):10859-66. doi: 10.1523/JNEUROSCI.23-34-10859.2003.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Antipsychotic Agents / pharmacology*
  • Cell Separation
  • Dopamine / biosynthesis*
  • Enzyme Inhibitors / pharmacology
  • Haloperidol / pharmacology*
  • Mesencephalon / cytology
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Polymerase Chain Reaction
  • Potassium / metabolism
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tetraethylammonium / pharmacology
  • Time

Substances

  • Antipsychotic Agents
  • Enzyme Inhibitors
  • Potassium Channel Blockers
  • Potassium Channels
  • Tetraethylammonium
  • Mitogen-Activated Protein Kinases
  • Haloperidol
  • Potassium
  • Dopamine