Baclofen, motion sickness susceptibility and the neural basis for velocity storage.
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.
Cohen
Bernard
B
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA. Bernard.Cohen@mssm.edu
Dai
Mingjia
M
Yakushin
Sergei B
SB
Raphan
Theodore
T
D000818:Animals; D001418:Baclofen / Q000494:pharmacology / Q000627:therapeutic use*; D004198:Disease Susceptibility; D005133:Eye Movements / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D019416:Head Movements / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008252:Macaca fascicularis; D008959:Models, Neurological; D009041:Motion Sickness / Q000188:drug therapy*; D009760:Nystagmus, Physiologic / Q000187:drug effects / Q000502:physiology; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects / Q000502:physiology*; D012399:Rotation
D018755:GABA Agonists; D001418:Baclofen