title: Chlorpromazine inhibits cochlear function in guinea pigs.
abstract: Outer hair cell (OHC) electromotility provides mechanical positive feedback that functions as the cochlear amplifier. In isolated OHCs, chlorpromazine shifts the electromotility voltage-displacement transfer function in a depolarizing direction without affecting its magnitude. This study sought to measure the effects of chlorpromazine on cochlear function in vivo. Salicylate, a drug that greatly reduces the magnitude of electromotility, was used for comparison. Perilymphatic perfusion of the guinea pig cochlea with chlorpromazine or salicylate increased the compound action potential (CAP) threshold across the frequency spectrum (1-20 kHz). Both drugs also increased distortion product otoacoustic emission (DPOAE) thresholds in the higher frequencies (10-20 kHz). Complete reversibility of these effects occurred after washout. Both drugs demonstrated concentration-dependent reductions in cochlear function that followed sigmoidal curves with similar fits to previously reported results in isolated OHCs. The endolymphatic potential was not affected by either of these drugs. Thus, chlorpromazine inhibits cochlear function in a manner consistent with what would be expected from data in isolated OHCs. This suggests that shifting the electromotility transfer function correspondingly reduces the gain of the cochlear amplifier.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, CA 94143-0342, USA. jso@bcm.tmcu.edu
authors.forename: John S
authors.initials: JS
authors.lastname: Oghalai
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004710:Endolymph / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000502:physiology; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D010498:Perilymph / Q000502:physiology; D012980:Sodium Salicylate / Q000494:pharmacology; D013136:Spiral Ganglion / Q000502:physiology; D013316:Stria Vascularis / Q000187:drug effects / Q000502:physiology
chemical_list: D016861:Cyclooxygenase Inhibitors; D018492:Dopamine Antagonists; D002746:Chlorpromazine; D012980:Sodium Salicylate