The role of GABAB receptors in the vestibular oculomotor system in mice

• Published in: Behavioural brain research 2016-04, Vol.302, p.152-159
• Main Authors: Shimizu, Naoki, Wood, Scott, Kushiro, Keisuke, Perachio, Adrian, Makishima, Tomoko
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Baclofen; Baclofen - pharmacology; Dose-Response Relationship, Drug; Eye movement; Eye Movements - drug effects; GABA-B Receptor Agonists - pharmacology; Gamma-amino butyric acid (GABA); Male; Mice; Mice, Inbred C57BL; Nystagmus, Physiologic - drug effects; Off-vertical axis rotation (OVAR); Otolithic Membrane - drug effects; Psychophysics; Receptors, GABA-A - metabolism; Reflex, Vestibulo-Ocular - drug effects; Rotation; Velocity storage mechanism (VSM); Vestibulo-ocular reflex (VOR)
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2016.01.017

•We studied effects of systemic administration of baclofen on mice eye movements.•Large effects were shown on the responses through higher-order vestibular system.•Obtained findings were in good agreement with the findings of nodulectomized mice.•Well-conserved GABAergic system in oculomotor pathway across mammals was suggested.•For study of GABA transmission, diversity of vestibular system should be considered. Systemic administration of a gamma-amino butyric acid type B (GABAB) receptor agonist, baclofen, affects various physiological and psychological processes. To date, the effects on oculomotor system have been well characterized in primates, however those in mice have not been explored. In this study, we investigated the effects of baclofen focusing on vestibular-related eye movements. Two rotational paradigms, i.e. sinusoidal rotation and counter rotation were employed to stimulate semicircular canals and otolith organs in the inner ear. Experimental conditions (dosage, routes and onset of recording) were determined based on the prior studies exploring the behavioral effects of baclofen in mice. With an increase in dosage, both canal and otolith induced ocular responses were gradually affected. There was a clear distinction in the drug sensitivity showing that eye movements derived from direct vestibulo-ocular reflex pathways were relatively unaltered, while the responses through higher-order neural networks in the vestibular system were substantially decreased. These findings were consistent with those observed in primates suggesting a well-conserved role of GABAB receptors in the oculomotor system across frontal-eyed and lateral-eyed animals. We showed here a previously unrecognized effect of baclofen on the vestibular oculomotor function in mice. When interpreting general animal performance under the drug, the potential contribution of altered balance system should be taken into consideration.