Abstract
The aim of this study was to determine the effects of chronic infusion of a GABAA receptor agonist/antagonist into the ipsilateral or contralateral vestibular nuclear complex (VNC) on vestibular compensation, the process of behavioral recovery that occurs after unilateral vestibular deafferentation (UVD). This was achieved by a mini-osmotic pump that infused, over 30 h, muscimol or gabazine into the ipsilateral or contralateral VNC. Spontaneous nystagmus (SN), yaw head tilt (YHT), and roll head tilt (RHT) were measured. Infusion of muscimol or gabazine into either the ipsilateral or the contralateral VNC had little effect on SN compensation. In contrast, infusion of muscimol (250, 500, and 750 ng) into the contralateral VNC and gabazine (31.25, 62.5, and 125 ng) into the ipsilateral VNC significantly affected YHT and RHT (p < 0.05), but not their rate of compensation (p > 0.05). Interestingly, the effects of muscimol and gabazine on YHT and RHT were consistent throughout the first 30 h post-UVD. Infusion of muscimol (62.5, 125, and 250 ng) into the ipsilateral VNC and gabazine (125, 375, and 750 ng) into the contralateral VNC had little effect on YHT and RHT or their rate of compensation. These results suggest that the ipsilateral gabazine and contralateral muscimol infusions are modifying the expression of the symptoms without altering the mechanism of compensation. Furthermore, the neurochemical mechanism responsible for vestibular compensation can cope with the both the GABAA receptor-mediated and the UVD-induced decrease in resting activity.
Footnotes
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This research was supported by a Project Grant from the Health Research Council of New Zealand (to P.F.S. and C.L.D.). C.M.G. was supported by a Foundation for Research, Science and Technology Bright Futures Ph.D. Scholarship.
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doi:10.1124/jpet.104.082172.
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ABBREVIATIONS: UVD, unilateral vestibular deafferentation; VNC, vestibular nuclear complex; SN, spontaneous nystagmus; THIP, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride; YHT, yaw head tilt; RHT, roll head tilt; SR 95531, 2-(3′carboxy-2′-propyl)-3-amino-6-p-methoxyphenylpyridazinium bromide; ANOVA, analysis of variance.
- Received December 12, 2004.
- Accepted January 31, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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