title: Auditory and vestibular defects and behavioral alterations after neonatal administration of streptomycin to Lewis rats: Similarities and differences to the circling (ci2/ci2) Lewis rat mutant.
abstract: The clinical usefulness of aminoglycoside antibiotics is limited by their ototoxicity. In rodents, damage to the inner ear is often associated with rotational behavior and locomotor hyperactivity reminiscent of such behaviors resulting from an imbalance of forebrain dopamine systems. Based on previous observations in the circling (ci2/ci2) Lewis (LEW) rat mutant, a spontaneous mutation leading to hair cell loss, deafness, impairment of vestibular functions, lateralized circling, hyperactivity and alterations in the nigrostriatal dopamine system, we have recently hypothesized that vestibular defects during postnatal development, independent of whether induced or inherited, lead to secondary changes in the dopaminergic system within the basal ganglia, which would be a likely explanation for the typical behavioral phenotype seen in such models. In the present study, we directly compared the phenotype induced by streptomycin in LEW rats with that of the ci2 LEW rat mutant. For this purpose, we treated neonatal LEW rats over 3 weeks by streptomycin, which induced bilateral degeneration of cochlear and vestibular hair cells. Following this treatment period, the behavioral syndrome of the streptomycin-treated animals, including the lateralized rotational behavior, was almost indistinguishable from that of ci2 mutant rats. However, in contrast to the ci2 mutant rat, all alterations, except the hearing loss, were only transient, disappearing between 7 and 24 weeks following treatment. In conclusion, in line with our hypothesis, vestibular defects induced in normal LEW rats led to the same phenotypic behavior as the inherited vestibular defect of ci2 mutant rats. However, with increasing time for recovery, adaptation to the vestibular impairment developed in streptomycin-treated rats, while all deficits persisted in the mutant animals. At least in part, the transient nature of the abnormal behaviors resulting from treatment with streptomycin could be explained by adaptation to the vestibular impairment by the use of visual cues, which is not possible in ci2 rats because of progressive retinal degeneration in these mutants. Although further experiments are needed to prove this hypothesis, the present study shows that direct comparisons between these two models serve to understand the mechanisms underlying the complex behavioral phenotype in rodents with vestibular defects and how these defects are compensated.
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, Hannover, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Schirmer
authors.forename: Alexander
authors.initials: A
authors.lastname: Kaiser
authors.forename: Alina
authors.initials: A
authors.lastname: Lessenich
authors.forename: Sven
authors.initials: S
authors.lastname: Lindemann
authors.forename: Maren
authors.initials: M
authors.lastname: Fedrowitz
authors.forename: Manuela
authors.initials: M
authors.lastname: Gernert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
mesh_terms: D000505:Alopecia / Q000235:genetics; D000818:Animals; D001307:Auditory Perception; D001522:Behavior, Animal; D003638:Deafness / Q000235:genetics; D006311:Hearing Disorders / Q000235:genetics* / Q000503:physiopathology; D009043:Motor Activity / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D014722:Vestibule, Labyrinth / Q000503:physiopathology*