title: The effects of L-NAME on vestibular compensation and NOS activity in the vestibular nucleus, cerebellum and cortex of the guinea pig.
abstract: Nitric oxide (NO) has been implicated in the processes by which animals recover from peripheral vestibular damage ('vestibular compensation'). However, few data exist on the dose-response effects of systemic administration of the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on the vestibular compensation process. The aim of this study was to investigate the effects on compensation of 5, 10, 50 or 100 mM L-NAME administered by s.c osmotic minipump for 50 h following unilateral vestibular deafferentation (UVD) in guinea pig, either commencing the drug treatment at 4 h pre-UVD or at the time of the UVD (i.e., post-UVD). Post-UVD treatment with L-NAME, at any of the four concentrations used, had no effect on the compensation of spontaneous nystagmus (SN), yaw head tilt (YHT) or roll head tilt (RHT). By contrast, pre-UVD treatment with 100 mM L-NAME resulted in a significant decrease in SN frequency (P<0.05) and a change in the rate of its compensation (P<0.0005). Pre-UVD L-NAME resulted in a significant increase in the overall magnitude of YHT (P<0.005); however, post-hoc comparisons revealed no significant differences between any specific L-NAME and vehicle groups. Pre-UVD L-NAME had no effect on RHT at any concentration. Analysis of NOS activity in the pre-UVD L-NAME treatment groups at 50 h post-UVD showed that only 100 mM L-NAME resulted in a significant decrease in NOS activity in the contralateral medial vestibular nucleus (MVN)/prepositus hypoglossi (PH) (P<0.05) and that NOS activity in the ipsilateral MVN/PH was not significantly affected. However, NOS activity was significantly inhibited in the bilateral cerebellum and cortices for several concentrations of L-NAME. These results suggest that pre-UVD systemic administration of L-NAME can significantly increase the rate of SN compensation in guinea pig and that this effect is correlated with inhibition of NOS activity in several regions of the CNS.
authors.affiliation: Vestibular Research Group, Department of Pharmacology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand.
authors.forename: S
authors.initials: S
authors.lastname: Paterson
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.forename: P F
authors.initials: PF
authors.lastname: Smith
authors.forename: C L
authors.initials: CL
authors.lastname: Darlington
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000201:enzymology*; D002540:Cerebral Cortex / Q000201:enzymology*; D003714:Denervation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007839:Functional Laterality; D006168:Guinea Pigs; D019416:Head Movements; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009760:Nystagmus, Physiologic; D014722:Vestibule, Labyrinth / Q000187:drug effects / Q000201:enzymology / Q000294:innervation / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester