Abstract
Biochemical and pharmacologic studies suggest a role for the ornithine decarboxylase—polyamine system as a modulator of behavioral changes during vestibular compensation. α-Difluoromethylornithine specifically blocks the rate-limiting step of polyamine biosynthesis. To assess the effects of α-difluoromethylornithine on the acute phase of postural compensation, guinea pigs were divided into groups subjected to either unilateral labyrinthectomy only (n = 7), α-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. α-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 α-difluoromethylornithine in compensated guinea pigs. Fully compensated animals from phase 1 were randomly assigned to receive α-difluoromethylornithine (500 mg/kg/day) or saline once daily for 4 days. Only 33% of α-difluoromethylornithine animals maintained air-righting, compared with 100% of saline-treated animals (p = 0.003). Maximum trunk curvature was greater in the α-difluoromethylornithine group (p = 0.02). Thus α-difluoromethylornithine not only delayed the time course for postural recovery after unilateral labyrinthectomy, it also transiently disrupted the maintenance of the compensated state.
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