Effects of furosemide on cochlear neural activity, central hyperactivity and behavioural tinnitus after cochlear trauma in guinea pig.
Cochlear trauma causes increased spontaneous activity (hyperactivity) to develop in central auditory structures, and this has been suggested as a neural substrate for tinnitus. Using a guinea pig model we have previously demonstrated that for some time after cochlear trauma, central hyperactivity is dependent on peripheral afferent drive and only later becomes generated intrinsically within central structures. Furosemide, a loop diuretic, reduces spontaneous firing of auditory afferents. We investigated in our guinea pig model the efficacy of furosemide in reducing 1) spontaneous firing of auditory afferents, using the spectrum of neural noise (SNN) from round window recording, 2) hyperactivity in inferior colliculus, using extracellular single neuron recordings and 3) tinnitus at early time-points after cochlear trauma. Tinnitus was assessed using gap prepulse inhibition of acoustic startle (GPIAS). Intraperitoneal furosemide, but not saline, caused a marked decrease in both SNN and central hyperactivity. Intracochlear perfusion with furosemide similarly reversed central hyperactivity. In animals in which GPIAS measurements suggested the presence of tinnitus (reduced GPIAS), this could be reversed with an intraperitoneal injection with furosemide but not saline. The results are consistent with furosemide reducing central hyperactivity and behavioural signs of tinnitus by acting peripherally to decrease spontaneous firing of auditory afferents. The data support the notion that hyperactivity may be involved in the generation of tinnitus and further suggest that there may be a therapeutic window after cochlear trauma using drug treatments that target peripheral spontaneous activity.
The Auditory Laboratory, School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia.
Wilhelmina H A M
WH
Mulders
The Auditory Laboratory, School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia.
Kristin M
KM
Barry
The Auditory Laboratory, School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia.
Donald
D
Robertson
D000200:Action Potentials; D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000503:physiopathology; D003051:Cochlea / Q000187:drug effects / Q000293:injuries*; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006168:Guinea Pigs; D007245:Inferior Colliculi / Q000187:drug effects* / Q000503:physiopathology; D007274:Injections, Intraperitoneal; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D014012:Tinnitus / Q000188:drug therapy* / Q000503:physiopathology
D004232:Diuretics; D005665:Furosemide