The effects of L-NAME on vestibular compensation and NOS activity in the vestibular nucleus, cerebellum and cortex of the guinea pig.
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.
Paterson
S
S
Vestibular Research Group, Department of Pharmacology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand.
Zheng
Y
Y
Smith
P F
PF
Darlington
C L
CL
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*
D004791:Enzyme Inhibitors; D019331:NG-Nitroarginine Methyl Ester