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 (unila teral vestibular deafferentation, UVD) results in a syndrome of ocular moto r and postural disorders, many of which disappear over time in a process of behavioural recovery known as vestibular compensation. Excitatory amino ac id receptors, in particular the N-methyl-D-aspartate (NMDA) receptor, have been implicated in vestibular compensation; however, the metabotropic gluta mate receptors (mGluRs) have not been studied in this context. The aim of t his study was to determine whether group I mGluRs in the brainstem vestibul ar nucleus complex (VNC) ipsilateral to the UVD are involved in vestibular compensation of the static symptoms of UVD in guinea pig. The selective gro up I mGluR antagonist (RS)-1-aminoindan-1,5,dicarboxylic acid (AIDA) was co ntinuously infused into the ipsilateral VNC for 30-min pre-UVD and 30-min p ost-UVD by cannula, at a rate of 1 mu l/h, using one of four doses: 0.1 fg, 0.1 pg, 0.1 ng or 0.1 mu g (n=5 animals in each case). In control conditio ns, a 0.1-fg (n=4) or 0.1-mu g (n=5) NaOH vehicle was infused into the ipsi lateral VNC using the same protocol. In order to control for the possibilit y that AIDA disrupted spontaneous neuronal activity in the VNC in normal an imals, 0.1 mu g AIDA (n=4) or 0.1 mu g 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) we re measured at 8, 10, 12, 15, 20, 25, 30, 35, 45 and 50 h post-UVD. In addi tion, the righting reflex latency (RRL) was measured in labyrinthine-intact animals in order to assess whether AIDA impaired motor coordination in lab yrinthine-intact animals. In UVD animals, the highest dose of AIDA signific antly reduced SN frequency and changed its rate of compensation (P<0.001 an d P<0.0001, respectively). This dose of AIDA also caused a significant redu ction in YHT (P<0.005) as well as a significant change in its rate of compe nsation (P<0.0001). However, RHT was not significantly affected. In the lab yrinthine-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 an d some postural symptoms following UVD. Furthermore, group I mGluRs may not contribute to the resting activity of vestibular nucleus neurons.