Effect of Fluoxetine and Acacetin on Central Vestibular Compensation in an Animal Model of Unilateral Peripheral Vestibulopathy

Damage to the peripheral vestibular system is known to generate a syndrome characterized by postural, locomotor, oculomotor, perceptual and cognitive deficits. Current pharmacological therapeutic solutions for these pathologies lack specificity and efficacy. Recently, we demonstrated that apamin, a specific SK channel blocker, significantly reduced posturo-locomotor and oculomotor deficits in the cat and the rat. The aim of the present study was to test the antivertigo potential of compounds belonging to the SK antagonists family, such as Acacetin and Fluoxetine. Young rats were subjected to unilateral ototoxic lesions of the vestibular organ using transtympanic administration of arsanilic acid (TTA) to evoke unilateral vestibular loss (UVL). Vestibular syndrome was monitored using behavioural evaluation allowing appreciation of the evolution of static and dynamic posturolocomotor deficits. A significant effect of the TTA insult was only found on the distance moved, the mean body velocity and the not moving time. From day 2 to week 2 after TTA, the distance moved and the mean body velocity were significantly decreased, while the not moving time was significantly increased. Acacetin does not evoke any significant change in the vestibular posturo-locomotor parameters' kinetics. Administration of Fluoxetine two weeks before TTA and over three weeks after TTA (preventive group) does not evoke any significant change in the vestibular posturo-locomotor parameters' kinetics. Administration of Fluoxetine from three weeks after TTA significantly delayed the functional recovery. This study demonstrates that Acacetin or Fluoxetine in TTA vestibulo-injured rats does not bring any significant benefit on the posture and locomotor balance deficits.