Assessment of drug‐induced changes in visual processing using the optomotor response in rodents (1060.5)

Abstract

Drug‐induced ocular toxicity is one of the major obstacles that would halt clinical development of a drug. One nonclinical method of detecting alterations in visual processing may be to assess the effects of a drug on optomotor responses (OR). The present study examined OR in rats as an indication of visual dysfunction using two compounds, quinine and sodium iodate, that are known to produce visual impairment in humans. Male Wistar Han rats were administered vehicle or quinine (100 or 300 mg/kg, p.o.) and OR was assessed at predose, 30, and 120 minutes postdose using the OptoMotry system (CerebralMechanics Inc.). Quinine elicited a dose‐dependent decrease in OR at both timepoints . Furthermore, locomotor activity was assessed in these rats at 30 minutes postdose. Quinine (100 mg/kg, p.o.) resulted in a trend towards decreased activity whereas 300 mg/kg produced significant decreases in locomotor activity. This suggests that decreases in activity did not interfere with the OR at 100 mg/kg but may have affected the measurement at 300 mg/kg. In another study, OR was assessed in rats up to 4 weeks after administration of sodium iodate (50 mg/kg, i.v.) Sodium iodate produced a significant reduction in OR from 2 hours to 1 week postdose. Reduced locomotor activity was detected at 2 hours postdose in sodium iodate‐treated rats. These decreases subsided by 24 hours postdose, suggesting that decreased OR observed at 24 hours and 1 week postdose were not due to decreased activity. Although factors such as sedation may interfere with the ability to assess the OR, the results were in agreement with published literature. Altogether, assessing OR in rodents may be beneficial in characterizing the adverse effects of test compounds on visual perception and acuity.