alpha-Difluoromethylornithine delays behavioral recovery and induces decompensation after unilateral labyrinthectomy.
Biochemical and pharmacologic studies suggest a role for the ornithine decarboxylase-polyamine system as a modulator of behavioral changes during vestibular compensation. alpha-Difluoromethylornithine specifically blocks the rate-limiting step of polyamine biosynthesis. To assess the effects of alpha-difluoromethylornithine on the acute phase of postural compensation, guinea pigs were divided into groups subjected to either unilateral labyrinthectomy only (n = 7), alpha-difluoromethylornithine (500 mg/kg/day) for 4 days before labyrinthectomy (n = 10), equivalent volumes of saline for 4 days before labyrinthectomy (n = 8), and sham operations (n = 5). Yaw head tilt and roll head tilt, trunk curvature, and air-righting reflex were measured at baseline and at regular intervals up to 4 weeks. alpha-Difluoromethylornithine significantly delayed recovery of normal air-righting but had no effect on yaw head tilt, roll head tilt, and trunk curvature. We also evaluated effects of alpha-difluoromethylornithine in compensated guinea pigs. Fully compensated animals from phase 1 were randomly assigned to receive alpha-difluoromethylornithine (500 mg/kg/day) or saline once daily for 4 days. Only 33% of alpha-difluoromethylornithine animals maintained air-righting, compared with 100% of saline-treated animals (p = 0.003). Maximum trunk curvature was greater in the alpha-difluoromethylornithine group (p = 0.02). Thus alpha-difluoromethylornithine not only delayed the time course for postural recovery after unilateral labyrinthectomy, it also transiently disrupted the maintenance of the compensated state.
Backous
D D
DD
Clayton Neurotology Laboratory, Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, TX 77030.
Henley
C M
CM
Dunn
J K
JK
Jenkins
H A
HA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007758:Ear, Inner / Q000601:surgery*; D000518:Eflornithine / Q000494:pharmacology*; D006168:Guinea Pigs; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D011187:Posture; D011897:Random Allocation
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D009955:Ornithine Decarboxylase; D000518:Eflornithine