Effects of baclofen on the angular vestibulo-ocular reflex.
The purpose of this study was to determine the effect of baclofen, a GABA(B) 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 g (1), 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, T (VOR), and a gain g (0) 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 T (VOR), g (0), and g (1) 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 degrees /s, and g (1), g (0), 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 g (0) at dosages of 20 and 30 mg, but had no effect on g (1). Small reductions in g (0) 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 GABA(B) terminals in the vestibular nuclei are responsible for the control of the afferent input to velocity storage through g (0), while the post-synaptic GABA(B) 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 GABA(A) receptors are utilized in the direct aVOR pathway.
Dai
Mingjia
M
Department of Neurology, Mount Sinai School of Medicine, 1 East 100th Street, Box 1135, New York, NY 10029-6574, USA. mingjia.dai@mssm.edu
Raphan
Theodore
T
Cohen
Bernard
B
D000328:Adult; D001418:Baclofen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004584:Electronystagmography; D005133:Eye Movements / Q000187:drug effects; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009760:Nystagmus, Physiologic; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects*; D013997:Time Factors
D018755:GABA Agonists; D001418:Baclofen