AN ELECTROPHYSIOLOGICAL METHOD FOR DETECTING VISUAL TOXICITY IN UNRESTRAINED RATS

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Abstract
Methods for recording the electroretinogram (ERG) and the visually evoked potential (VEP) in unrestrained rats were developed and used to test the long-term toxicity of diaminodiphenoxybutane (DAPB). The electrodes for recording the ERG and VEP were implanted chronically in the sclera of the eye and on the surface of the visual cortex, respectively. Both the ERG and VEP were recorded from unrestrained rats using a slip ring that allows the rat free movement without twisting the cables. Fifty responses to repetitive photic stimulation at 10-s intervals were averaged by means of a minicomputer. The waveforms of the ERG consisted of an initial negative wave (a-wave), followed by a positive wave (b-wave) with 3-4 oscillatory potentials on the rising slope. The VEP consisted of an initial positive wave (P1 wave), followed by a large negative wave (N1 wave) and late positive and negative deflections. The amplitudes of these components of the ERG and VEP varied considerably from animal to animal; these components within the same animal were reproducible within a 20% variation in amplitudes and a 10% variation in latencies measured from ERG and VEP obtained repeatedly for 7 wk in 6 control rats. Using this technique, the effects of DAPB, a retinotoxic compound, on ERG and VEP were studied. DAPB produced a marked dose-dependent decrease in the amplitudes and prolongation in the latencies of the ERG after a single i.v. injection at doses of 50 and 70 mg/kg. The VEP was also suppressed in parallel with the change of the ERG. This recording technique for ERG and VEP is apparently useful for evaluating the visual toxicity of drugs in unrestrained rats.

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