Increases in spontaneous neural activity in the hamster dorsal cochlear nucleus following cisplatin treatment: a possible basis for cisplatin-induced tinnitus.
Recent investigations in the hamster have implicated increased spontaneous activity (SA) in the dorsal cochlear nucleus (DCN) as a contributing factor in the etiology of tinnitus induced by intense sound exposure. It might therefore be expected that increased SA would also develop in the DCN of hamsters treated with cisplatin, another cause of tinnitus. We tested this hypothesis by measuring the effects of cisplatin on SA in the DCN. Adult hamsters were divided into three groups, each receiving five injections of cisplatin at one of the following doses: 3 mg/kg, 2.25 mg/kg, or 1.5 mg/kg. Each group had corresponding controls receiving injections of isotonic saline. The effects of cisplatin were studied electrophysiologically 1 month after treatment by recording multiunit SA on the surface of the DCN. Measurements of SA were obtained in three rows of 13-15 locations spaced roughly 100 microm apart and spanning the length of the DCN along the tonotopic axis. Effects of cisplatin were evaluated by comparing plots of mean SA vs. tonotopic locus for cisplatin-treated groups with those of their corresponding untreated control groups. The results demonstrated a consistently higher level of SA in cisplatin-treated groups than in untreated controls. Whereas the highest rates of mean SA in control groups were between 10 and 15 events/s, the highest mean spontaneous rates in cisplatin-treated groups were between 25 and 38 events/s. The cisplatin-induced hyperactivity was greatest in the medial half of the DCN corresponding to the high frequency portion of the tonotopic range. These results suggest that cisplatin treatment is an effective inducer of hyperactivity in the DCN. This hyperactivity may be an important neural correlate of cisplatin-induced tinnitus.
Rachel
John D
JD
Department of Otolaryngology, Head and Neck Surgery 5E-UHC, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Kaltenbach
James A
JA
Janisse
James
J
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D017626:Cochlear Nucleus / Q000187:drug effects* / Q000503:physiopathology*; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006317:Hearing Loss, Noise-Induced / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008647:Mesocricetus; D014012:Tinnitus / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology*
D000970:Antineoplastic Agents; D002945:Cisplatin