title: Long-term K+ channel-mediated dampening of dopamine neuron excitability by the antipsychotic drug haloperidol.
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.
authors.affiliation: Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Hahn
authors.forename: Tonia E
authors.initials: TE
authors.lastname: Tse
authors.forename: Edwin S
authors.initials: ES
authors.lastname: Levitan
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002469:Cell Separation; D004298:Dopamine / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D013995:Time
chemical_list: D014150:Antipsychotic Agents; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; D020928:Mitogen-Activated Protein Kinases; D006220:Haloperidol; D011188:Potassium; D004298:Dopamine