Effects of arteether on an auditory radial-arm maze task in rats

We evaluated the behavioral and neural toxicity of the artemisinin antimala rial compound, arteether (AE), using a novel radial-arm maze procedure. We have previously shown that AE can produce a distinctive pattern of neurotox icity in the brainstem and that auditory nuclei are particularly vulnerable . Thus, we assessed performance which depended upon auditory processing. We trained rats to choose one of eight arms of a radial maze, depending upon which arm served as the source of a white noise stimulus. Correct responses produced food reinforcement while incorrect choices had no programmed cons equences. When the task was acquired, AE (25 mg/kg/day; n = 7) or oil Vehic le (n = 7) was administered (intramuscularly) for seven consecutive days. B ehavioral sessions were conducted during the days of drug administrations a cid for 7 days following drug administrations. Subsequently, histopathology was conducted and a quantitative assessment of the nucleus trapezoideus wa s made. AE produced a progressive deficit in performance on the maze task. That is, accuracy decreased, choice latency increased, and the number of tr ials completed decreased. Moreover, the greatest deficits were observed dur ing the period following drug administrations. AE-treated rats revealed mar ked damage in the nucleus trapezoideus. The damage included chromatolysis, necrosis, and gliosis. Vehicle-treated rats did not show performance defici ts or neuropathology. These results extend earlier studies and show that AE can produce damage in the n. trapezoideus of rats, which is associated wit h performance deficits on a complex auditory task. Thus, the auditory radia l-arm maze task is a useful tool for assessing AE-induced toxicity. (C) 200 1 Elsevier Science Inc. All rights reserved.