title: slo K(+) channel gene regulation mediates rapid drug tolerance.
abstract: Changes in neural activity caused by exposure to drugs may trigger homeostatic mechanisms that attempt to restore normal neural excitability. In Drosophila, a single sedation with the anesthetic benzyl alcohol changes the expression of the slo K(+) channel gene and induces rapid drug tolerance. We demonstrate linkage between these two phenomena by using a mutation and a transgene. A mutation that eliminates slo expression prevents tolerance, whereas expression from an inducible slo transgene mimics tolerance in naive animals. The behavioral response to benzyl alcohol can be separated into an initial phase of hyperkinesis and a subsequent phase of sedation. The hyperkinetic phase causes a drop in slo gene expression and makes animals more sensitive to benzyl alcohol. It is the sedative phase that stimulates slo gene expression and induces tolerance. We demonstrate that the expression level of slo is a predictor of drug sensitivity.
authors.affiliation: Section of Neurobiology, University of Texas, Austin, TX 78712, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Yazan M
authors.initials: YM
authors.lastname: Al-Hasan
authors.forename: Leo E
authors.initials: LE
authors.lastname: Larios
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Bohm
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Atkinson
mesh_terms: D000818:Animals; D019905:Benzyl Alcohol / Q000494:pharmacology; D016292:Procedural Sedation; D004330:Drosophila; D029721:Drosophila Proteins; D004361:Drug Tolerance; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006948:Hyperkinesis; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009154:Mutation; D024681:Potassium Channels, Calcium-Activated / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012333:RNA, Messenger; C494844:slo protein, Drosophila; D019905:Benzyl Alcohol