A new goldfish model to evaluate pharmacokinetic and pharmacodynamic effects of drugs used for motion sickness in different gravity loads

This paper proposes a new goldfish model to predict pharmacodynamic/pharmac okinetic effects of drugs used to treat motion sickness administered in dif fering gravity loads. The assumption of these experiments is that the vesti bular system is dominant in producing motion sickness and that the visual s ystem is secondary or of small import in the production of motion sickness. Studies will evaluate the parameter of gravity and the contribution of vis ion to the role of the neurovestibular system in the initiation of motion s ickness with and without pharmacologic agents. Promethazine will be studied first. A comparison of data obtained in different groups of goldfish will be done (normal vs. acutely and chronically bilaterally blinded vs. sham op erated). Some fish will be bilaterally blinded 10 months prior to initiatio n of the experiment (designated the chronically bilaterally blinded group o f goldfish) to evaluate the neuroplasticity of the nervous system and the a ssociated return of neurovestibular function. Data will be obtained under d iffering gravity loads with and without a pharmacological agent for motion sickness. Experiments will differentiate pharmacological effects on vision vs. neurovestibular input to motion sickness. Comparison of data obtained i n the normal fish and in acutely and chronically bilaterally blinded fish w ith those obtained in fish with intact and denervated otoliths will differe ntiate if the visual or neurovestibular system is dominant in response to a ltered gravity and/or drugs. Experiments will contribute to validation of t he goldfish as a model for humans since plasticity of the central nervous s ystem allows astronauts to adapt to the altered visual stimulus conditions of 0-g. Space motion sickness may occur until such an adaptation is achieve d. (C) 2001 Elsevier Science Ltd. All rights reserved.