Effects of intra-vestibular nucleus injection of the group I metabotropic glutamate receptor antagonist AIDA on vestibular compensation in guinea pigs.
Removal of the peripheral vestibular receptor cells in one inner ear (unilateral vestibular deafferentation, UVD) results in a syndrome of ocular motor and postural disorders, many of which disappear over time in a process of behavioural recovery known as vestibular compensation. Excitatory amino acid receptors, in particular the N-methyl-D-aspartate (NMDA) receptor, have been implicated in vestibular compensation; however, the metabotropic glutamate receptors (mGluRs) have not been studied in this context. The aim of this study was to determine whether group I mGluRs in the brainstem vestibular nucleus complex (VNC) ipsilateral to the UVD are involved in vestibular compensation of the static symptoms of UVD in guinea pig. The selective group I mGluR antagonist (RS)-1-aminoindan-1,5,dicarboxylic acid (AIDA) was continuously infused into the ipsilateral VNC for 30-min pre-UVD and 30-min post-UVD by cannula, at a rate of 1 microl/h, using one of four doses: 0.1 fg, 0.1 pg, 0.1 ng or 0.1 microg (n=5 animals in each case). In control conditions, a 0.1-fg (n=4) or 0.1-microg (n=5) NaOH vehicle was infused into the ipsilateral VNC using the same protocol. In order to control for the possibility that AIDA disrupted spontaneous neuronal activity in the VNC in normal animals, 0.1 microg AIDA (n=4) or 0.1 microg NaOH (n=2) was infused into the VNC in labyrinthine-intact animals. In both groups, static symptoms of UVD (i.e. spontaneous nystagmus, SN, yaw head tilt, YHT and roll head tilt, RHT) were measured at 8, 10, 12, 15, 20, 25, 30, 35, 45 and 50 h post-UVD. In addition, the righting reflex latency (RRL) was measured in labyrinthine-intact animals in order to assess whether AIDA impaired motor coordination in labyrinthine-intact animals. In UVD animals, the highest dose of AIDA significantly reduced SN frequency and changed its rate of compensation (P<0.001 and P<0.0001, respectively). This dose of AIDA also caused a significant reduction in YHT (P<0.005) as well as a significant change in its rate of compensation (P<0.0001). However, RHT was not significantly affected. In the labyrinthine-intact animals, AIDA infusion did not induce a UVD syndrome, nor did it significantly affect RRL. These results suggest that group I mGluRs in the ipsilateral VNC may be involved in the expression of ocular motor and some postural symptoms following UVD. Furthermore, group I mGluRs may not contribute to the resting activity of vestibular nucleus neurons.
Gliddon
C M
CM
Department of Pharmacology, School of Medical Sciences, University of Otago Medical School, Dunedin, New Zealand.
Sansom
A J
AJ
Smith
P F
PF
Darlington
C L
CL
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003714:Denervation; D007758:Ear, Inner / Q000294:innervation / Q000502:physiology / Q000601:surgery; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D019416:Head Movements / Q000187:drug effects / Q000502:physiology; D007189:Indans / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009759:Nystagmus, Pathologic / Q000503:physiopathology; D011493:Protein Kinase C / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D003689:Vestibular Nucleus, Lateral / Q000187:drug effects* / Q000502:physiology*
C095756:1-aminoindan-1,5-dicarboxylic acid; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D018094:Receptors, Metabotropic Glutamate; D011493:Protein Kinase C; D002118:Calcium