Effects of baclofen on the angular vestibulo-ocular reflex

Mingjia Dai, Theodore Raphan, Bernard Cohen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The purpose of this study was to determine the effect of baclofen, a GABAB agonist on the angular vestibulo-ocular reflex (aVOR). Model studies have shown that the aVOR comprises a "direct" pathway, which determines its high frequency gain g1, and an indirect "velocity storage" pathway, which determines its low frequency characteristics. Velocity storage can be characterized by an integrator with a dominant time constant, TVOR, and a gain g0 that couples afferent information from the semicircular canals to the integrator. Baclofen preferentially shortens the velocity storage time constant in monkeys, but its effect on TVOR, go, and g1 in humans is unknown. Six subjects were tested after administration of a placebo or of 10, 20, or 30 mg of baclofen in a double-blind design. The aVOR was elicited in darkness with steps of rotation at 138°/s, and g1, g0, and T VOR were determined from model fits of the slow phase velocity of the per- and post-rotatory nystagmus. Baclofen significantly reduced both T VOR and g0 at dosages of 20 and 30 mg, but had no effect on g1. Small reductions in g0 were associated with large reductions in vestibular output. Thus, baclofen does not affect the direct aVOR pathway in humans, but controls the low frequency aVOR in two ways: it limits the input to velocity storage and modulates its time constant. We speculate that pre-synaptic GABAB terminals in the vestibular nuclei are responsible for the control of the afferent input to velocity storage through g0, while the post-synaptic GABAB terminals are responsible for altering the duration of activity that reflects the time constant. The lack of effect of baclofen on the aVOR gain suggests that only GABAA receptors are utilized in the direct aVOR pathway.

Original languageEnglish
Pages (from-to)262-271
Number of pages10
JournalExperimental Brain Research
Volume171
Issue number2
DOIs
StatePublished - May 2006

Keywords

  • GABA
  • Nystagmus
  • Velocity storage
  • Vestibular

Fingerprint

Dive into the research topics of 'Effects of baclofen on the angular vestibulo-ocular reflex'. Together they form a unique fingerprint.

Cite this