Effects of chronic infusion of a GABAA receptor agonist or antagonist into the vestibular nuclear complex on vestibular compensation in the guinea pig.
The aim of this study was to determine the effects of chronic infusion of a GABA(A) 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 GABA(A) receptor-mediated and the UVD-induced decrease in resting activity.
Gliddon
Catherine M
CM
Vestibular Research Group, Department of Pharmacology and Toxicology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand.
Darlington
Cynthia L
CL
Smith
Paul F
PF
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D009760:Nystagmus, Physiologic / Q000187:drug effects; D011187:Posture / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D014726:Vestibular Nuclei / Q000187:drug effects* / Q000502:physiology
D011724:Pyridazines; D011963:Receptors, GABA-A; D009118:Muscimol; C049853:gabazine