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 d uring vestibular compensation. alpha-Difluoromethylornithine specifica lly blocks the rate-limiting step of polyamine biosynthesis. To assess the effects of alpha-difluoromethylornithine on the acute phase of po stural compensation, guinea pigs were divided into groups subjected to either unilateral labyrinthectomy only (n = 7), alpha-difluoromethylo rnithine (500 mg/kg/day) for 4 days before labyrinthectomy (n = 10), e quivalent 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 re gular intervals up to 4 weeks. alpha-Difluoromethylornithine significa ntly delayed recovery of normal air-righting but had no effect on yaw head tilt, roll head tilt, and trunk curvature. We also evaluated effe cts of alpha-difluoromethylornithine in compensated guinea pigs. Fully compensated animals from phase 1 were randomly assigned to receive al pha-difluoromethylornithine (500 mg/kg/day) or saline once daily for 4 days. Only 33% of alpha-difluoromethylornithine animals maintained ai r-righting, compared with 100% of saline-treated animals (p = 0.003). Maximum trunk curvature was greater in the alpha-difluoromethylornithi ne group (p = 0.02). Thus alpha-difluoromethylornithine not only delay ed the time course for postural recovery after unilateral labyrinthect omy, it also transiently disrupted the maintenance of the compensated state.