The vestibular system, a tool to study neurotoxicants in the central nervous system

Abstract: The vestibular and opto-ocular motor (VOOM) system in pigmented rats was investigated. Horizontal eye movements were recorded by the magnetic search coil technique during different kind of stimulations. The dynamics of the vestibular ocular reflex (VOR) and the optokinetic reflex (OKR) as well as the interaction of the two rel1exes were analysed. The ability to cancel nystagmus during vestibular and optokinetic stimulation was found to be comparable to "higher" animals.The experimental model was used to study the effects of toxicants and drugs on the VOOM system. Four different solvents, known to cause disturbances of the central nervous system (CNS), were tested. Acute exposure by inhalation of each solvent gave specific dose-response related effects in the VOOM system, most of which could be explained by an alteration of the cerebellar-vestibular circuit. However there were differences among the four solvents, the results indicating that different solvents should be considered as individual substances in toxicological CNS research.The effects of drugs, related to GABAB-transmission, were investigated.Baclofen, a GABAB-agonist, affected the VOR, the OKR and the interaction of these two in a dose-related way. All these effects could be blocked by CGP 35348, a GABAB-antagonist.The similarities in the effects of baclofen to the effects of toluene were striking. It was demonstrated that effects of toluene on the VOR could be blocked by CGP 35348 at a dose which did not cause any effects per se. It was concluded that some of the effects of toluene on the VOOM system were related to GABA-transmission, directly or indirectly.The VOOM system was also used in an otoneurological test battery to investigate the effects on the CNS in workers, long-term exposed to solvents. Dynamic posturography was also performed to obtain an indication of the integration of somatosensory, visual, and vestibular stimuli in the equilibrium system. Reduced ability to visual suppression, prolonged latency of saccades and pathology in the posturography tests were found in the solvent exposed group compared to results of a non-exposed healthy control group.All exposed worker had been evaluated for a possible chronic toxic encephalopathy (CTE) and were categorized in three groups non-CTE, incipient CTE, and CTE. These categories, based on psychometric test results and case histories of exposure and symptoms, were poorly correlated to the otoneurological findings. Even in the non-CTE group pathological findings were present. Lesions in the CNS revealed by an otoneurological investigation were apparently not found in the neuropsychological investigation. This indicates that an otoncurological test battery could contribute valuable information in the evaluation of long-term solvent exposed people suspected for CTE.The studies related above, demonstrate that the VOOM system is an useful tool in evaluating toxicological effects in the CNS.