title: High doses of salicylate causes prepulse facilitation of onset-gap induced acoustic startle response.
abstract: Prepulse inhibition of acoustic startle reflex (PPI), a well-established method for evaluating sensorimotor gating function, has been used to detect tinnitus in animal models. Reduced gap induced PPI (gap-PPI) was considered as a sign of tinnitus. The silent gap used in the test contains both onset and offset signals. Tinnitus may affect these cues differently. In this experiment, we studied the effects of a high dose of salicylate (250 mg/kg, i.p.), an inducer of reversible tinnitus and sensorineural hearing loss, on gap-PPI induced by three different gaps: an onset-gap with 0.1 ms onset and 25 ms offset time, an offset-gap with 25 ms onset and 0.1 ms offset time, and an onset-offset-gap with 0.1 ms onset and offset time. We found that the onset-gaps induced smaller inhibitions than the offset-gaps before salicylate treatment. The offset-gap induced PPI was significantly reduced 1-3h after salicylate treatment. However, the onset-gap caused a facilitation of startle response. These results suggest that salicylate induced reduction of gap-PPI was not only caused by the decrease of offset-gap induced PPI, but also by the facilitation induced by the onset-gap. Since the onset-gap induced PPI is caused by neural offset response, our results suggest that salicylate may cause a facilitation of neural response to an offset acoustical signal. Treatment of vigabatrin (60 mg/kg/day, 14 days), which elevates the GABA level in the brain, blocked the offset-gap induced PPI and onset-gap induced facilitation caused by salicylate. These results suggest that enhancing GABAergic activities can alleviate salicylate induced tinnitus.
authors.affiliation: Center for Hearing and Deafness, State University of New York at Buffalo, 3435 Main Street, Buffalo 14214, NY, USA; Department of Communicative Disorders and Sciences, State University of New York at Buffalo, 3435 Main Street, Buffalo 14214, NY, USA. Electronic address: weisun@buffalo.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Lauren
authors.initials: L
authors.lastname: Doolittle
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Flowers
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D012459:Salicylates / Q000008:administration & dosage*; D055139:Sensory Gating / Q000187:drug effects*
chemical_list: D012459:Salicylates
keywords: Facilitation; Gap induced prepulse inhibition; Salicylate; Tinnitus