title: The role of GABAB receptors in the vestibular oculomotor system in mice.
abstract: 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.
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address: naokish@naramed-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimizu
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA; Department of Psychology, Azusa Pacific University, Azusa California, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Wood
authors.affiliation: Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kushiro
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: Perachio
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address: tomakish@utmb.edu.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Makishima
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005133:Eye Movements / Q000187:drug effects*; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009760:Nystagmus, Physiologic / Q000187:drug effects; D010037:Otolithic Membrane / Q000187:drug effects; D011601:Psychophysics; D011963:Receptors, GABA-A / Q000378:metabolism*; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects*; D012399:Rotation
chemical_list: D058786:GABA-B Receptor Agonists; D011963:Receptors, GABA-A; D001418:Baclofen
keywords: Baclofen; Eye movement; Gamma-amino butyric acid (GABA); Off-vertical axis rotation (OVAR); Velocity storage mechanism (VSM); Vestibulo-ocular reflex (VOR)