Effects of baclofen on the angular vestibulo-ocular reflex

Area of Science:

• Neuroscience
• Vestibular System Physiology
• Pharmacology

Background:

• The angular vestibulo-ocular reflex (aVOR) is crucial for gaze stabilization during head movements.
• The aVOR comprises direct (high-frequency) and indirect (low-frequency, velocity storage) pathways.
• Baclofen's effect on human aVOR pathways, particularly velocity storage, remains largely unknown.

Purpose of the Study:

• To investigate the effects of baclofen, a GABA(B) agonist, on the human angular vestibulo-ocular reflex (aVOR).
• To determine baclofen's impact on the direct pathway gain (g(1)) and velocity storage parameters (T(VOR), g(0)).

Main Methods:

• A double-blind, placebo-controlled study involving six human subjects.
• Administration of varying dosages of baclofen (10, 20, 30 mg) or placebo.
• Elicitation of aVOR using rotational steps and analysis of nystagmus slow-phase velocity to model parameters.

Main Results:

• Baclofen significantly reduced the velocity storage time constant (T(VOR)) and input gain (g(0)) at 20 and 30 mg dosages.
• No significant effect of baclofen was observed on the direct pathway gain (g(1)).
• Baclofen's modulation of g(0) correlated with reduced vestibular output.

Conclusions:

• Baclofen influences the low-frequency aVOR in humans by modulating velocity storage, not the direct pathway.
• It limits afferent input to velocity storage (g(0)) and alters its time constant (T(VOR)).
• Findings suggest pre- and post-synaptic GABA(B) receptor involvement in vestibular nuclei for velocity storage control.