GABA_B receptors contribute to vestibular compensation after unilateral labyrinthectomy in pigmented rats

Abstract.

The horizontal vestibulo-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 recording of spontaneous eye movements in darkness, and the latter by estimating the slow-phase velocity (SPV) gain of compensatory eye movements during 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 36742 caused a decompensation by exaggerating the remaining ipsilesional eye drift. 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 aggravated SPV gain and phase lead asymmetries in UL rats during vestibular stimulation. Per- and post-rotatory nystagmus induced by velocity step stimulation revealed an imperfect velocity-storage function in UL animals, which was modulated by baclofen. An investigation of the baclofen effect on SPV gain asymmetry during different time intervals after chemical UL showed a completely developed effect on the 6th day. Bilateral flocculectomy did not alter the effects of baclofen on UL animals. It is concluded that physiological stimulation of GABA_B receptors contributes to minimise the vestibulo-oculomotor asymmetry during the partially compensated period after UL. Administration of an agonist or an antagonist changes the asymmetry towards the ipsi- or contralesional side, possibly by altering the spontaneous neuronal activity in the bilateral medial vestibular nuclei. The results are compatible with a hypothesis, supported by in vitro slice experiments, that the efficacy of GABA_B receptors is up-regulated on the ipsilesional side and down-regulated on the contralesional side.