Activation of serotonergic neurons during salicylate-induced tinnitus.

HYPOTHESIS Serotonergic neurons are activated during salicylate-induced tinnitus and modulate the cochlea during tinnitus. BACKGROUND During salicylate-induced tinnitus in the gerbil, neurons in the dorsal raphe nucleus were activated. Because approximately half of the neurons in this region are serotonergic, this indicates that serotonin (5-HT) might play a role in the mechanisms of central tinnitus. The goal of this study was to determine if serotonergic neurons are activated during salicylate-induced tinnitus. Furthermore, to determine if the same neurons might modulate the cochlea during tinnitus, neuroanatomic tract-tracing with 5-HT immunohistochemistry was used to determine if serotonergic neurons project to the gerbil cochlea. METHODS A randomized, prospective study was performed. Six gerbils were injected with salicylate (saline for controls). Four hours later, the gerbils were euthanized and perfused, and their brains were collected for immunohistochemical labeling of 5-HT and c-fos. For the tract-tracing, FluoroGold was injected into the cochleae of 3 gerbils. The gerbils were euthanized and perfused 4 to 11 days later, and the brains immunohistochemically were processed for 5-HT. RESULTS More serotonergic neurons expressed c-fos in the salicylate-injected animals compared with the controls. The increase was significant for 3 of the 8 major serotonergic cell groups including B7, B9, and the caudal linear nucleus. Despite robust labeling of olivocochlear and vestibular efferents with FluoroGold, 5-HT-labeled neurons containing FluoroGold were lacking. CONCLUSION Salicylate-induced tinnitus activates serotonergic neurons in rostral cell groups. Activation of these neurons is not likely to influence cochlear function directly but is likely to influence a number of auditory and nonauditory regions known to be involved with tinnitus.