GABA(B) receptors contribute to vestibular compensation after unilateral labyrinthectomy in pigmented rats

The horizontal vestibule-ocular reflex was studied in pigmented rats, which had been unilaterally, chemically labyrinthectomised 6-144 days previously . During this partially compensated stage after unilateral labyrinthectomy (UL), both static and dynamic deficits remain The former was evaluated by r ecording of spontaneous eye movements in darkness, and the latter by estima ting the slow-phase velocity (SPV) gain of compensatory eye movements durin g horizontal vestibular stimulation. The GABA(B) agonist baclofen caused a reversal of the remaining ipsilesional drift of the eyes in darkness into a nystagmus with a contralesional slow phase. The GABA(B) antagonist CGP 367 42 caused a decompensation by exaggerating the remaining ipsilesional eye d rift. Further, baclofen equilibrated or reversed the asymmetry between ipsi - and contralesional SPV gains during horizontal sinusoidal rotations at 0. 2 Hz and 0.8 Hz. This was achieved by an increase in the ipsilesional gain and a decrease in the contralesional gain. The phase lead during sinusoidal rotation (0.2 Hz) was larger following rotation to the lesioned side than to the intact side in UL rats. This asymmetry was reversed by baclofen. CGP 36742 inhibited the effects of baclofen, while the antagonist per se aggra vated SPV gain and phase lead asymmetries in UL rats during vestibular stim ulation. Per- and post-rotatory nystagmus induced by velocity step stimulat ion revealed an imperfect velocity-storage function in UL animals, which wa s modulated by baclofen. An investigation of the baclofen effect on SPV gai n asymmetry during different time intervals after chemical UL showed a comp letely developed effect on the 6th day. Bilateral flocculectomy did not alt er the effects of baclofen on UL animals. It is concluded that physiologica l stimulation of GABA(B) receptors contributes to minimise the vestibulo-oc ulomotor asymmetry during the partially compensated period after UL. Admini stration of an agonist or an antagonist changes the asymmetry towards the i psi- or contralesional side, possibly by altering the spontaneous neuronal activity in the bilateral medial vestibular nuclei. The results are compati ble with a hypothesis, supported by in vitro slice experiments, that the ef ficacy of GABA(B) receptors is up-regulated on the ipsilesional side and do wn-regulated on the contralesional side.