Reduction of the dominant time
constant (T(VOR)) of the angular vestibulo-ocular reflex (aVOR) by habituation is associated with a decrease in
motion sickness susceptibility.
Baclofen, a
GABA(b) agonist, reduces the time constant of the velocity storage integrator in the aVOR in a dose-dependent manner. The high frequency aVOR gain is unaltered by
baclofen. Here we demonstrate that the reduction in T(VOR) produced by
oral administration of 20 mg of
baclofen causes a significant reduction in
motion sickness susceptibility, tested with roll while rotating (RWR). These data show that
motion sickness susceptibility can be pharmacologically manipulated with a
GABA(b) agonist and support our conclusion that
motion sickness is generated through velocity storage. We also show how
baclofen acts on velocity storage at the neural level. A vestibular-plus-saccade (VPS) neuron was recorded in the rostral medial vestibular nucleus (rMVN) of a cynomolgus monkey, an area where we postulate that velocity storage is generated. The cell had a time constant during steps of velocity that was close to that of the T(VOR). After parenteral administration of
baclofen, there was a similar decrease in the time constants of the VPS neuron and the T(VOR). This is the first demonstration of the concurrence of unit and aVOR time constants before and after
baclofen. The data support the hypothesis that the velocity storage integrator is generated through activity of vestibular-only (VO) and VPS neurons in rMVN and suggest that
GABA(b) synapses on VO and VPS neurons are likely to be involved in the
baclofen-induced reduction in
motion sickness susceptibility.