Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats

0551560 - ÚEM 2022 RIV NL eng J - Journal Article
Rybalko, Natalia - Popelář, Jiří - Šuta, Daniel - Svobodová Buriánová, Jana - Alvaro, G.S. - Large, Ch.H. - Syka, Josef
Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats.
Hearing Research. Roč. 401, mar. (2021), č. článku 108139. ISSN 0378-5955. E-ISSN 1878-5891
R&D Projects: GA ČR(CZ) GA18-09692S
Institutional support: RVO:68378041
Keywords : AUT0 0 063 * AUT00202 * F344 rat * acoustic startle * gap-prepulse * temporal processing
OECD category: Neurosciences (including psychophysiology
Impact factor: 3.672, year: 2021
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/abs/pii/S037859552030410X?via%3Dihub

AUT0 0 063 and AUT00202 are novel pharmaceutical modulators of the Kv3 subfamily of voltage-gated K + channels. Kv3.1 channels, which control fast firing of many central auditory neurons, have been shown to decline with age and this may contribute to age-related deficits in central auditory processing. In the present study, the effects of the two novel compounds that specifically modulate Kv3 channels on au-ditory temporal processing were examined in aged (19-25-month-old) and young-adult (3-5 month-old) Fischer 344 rats (F344) using a behavioral gap-prepulse inhibition (gap-PPI) paradigm. The acoustic star-tle response (ASR) and its inhibition induced by a gap in noise were measured before and after drug ad-ministration. Hearing thresholds in tested rats were evaluated by the auditory brainstem response (ABR). Aged F344 rats had significantly higher ABR thresholds, lower amplitudes of ASR, and weaker gap-PPI compared with young-adult rats. No influence of AUT0 0 063 and AUT0 0202 administration was observed on ABR hearing thresholds in rats of both age groups. AUT0 0 063 and AUT00202 had suppressive effect on ASR of F344 rats that was more pronounced with AUT0 0 063. The degree of suppression depended on the dose and age of the rats. Both compounds significantly improved the gap-PPI performance in gap detection tests in aged rats. These results indicate that AUT0 0 063 and AUT0 0202 may influence intrinsic firing properties of neurons in the central auditory system of aged animals and have the potential to treat aged-related hearing disorders.
Permanent Link: http://hdl.handle.net/11104/0326825