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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Behavioral and neural toxicity of arteether in rats.
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Behavioral and neural toxicity of arteether in rats.

机译：蒿甲醚对大鼠的行为和神经毒性。

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摘要

Repeated administration of the artemisinin antimalarial compound, 3-arteether (AE) (25 mg/kg, i.m.) was evaluated in rats using a two-choice, discrete trial, auditory discrimination task and subsequent neurohistology. Rats were trained to choose one of two response levers following presentation of white noise or a tone + white noise. Increasing and decreasing the intensity of the tone increased and decreased discriminability, respectively, and differential reinforcement density produced systematic changes in response bias. AE (n = 5) or vehicle (n = 5) was injected daily (9-12 days). Initial injections of AE did not affect behavioral performance. Continuing daily injections produced significant decreases in choice accuracy and significant increases in choice reaction time. When overt signs of severe toxicity were observed, rats were sacrificed and significant neural pathology was observed in the nucleus trapezoideus of AE-treated rats. In a subsequent experiment, AE was injected for 3 (n = 5), 5 (n = 5), or 7 (n = 5), consecutive days and performance was examined for an additional 7 days. Behavioral disruption was only observed in rats receiving AE for 7 days and the greatest degree of disruption occurred after AE injections were completed. Histopathological examination showed significant neural pathology in the nuclei trapezoideus, superior olive, and ruber of rats receiving 7- and 5-day AE regimens, and in the nucleus trapezoideus of rats receiving the 3-day regimen. Thus, behavioral disruption reflected, but did not predict, neuropathology. These results confirm and extend earlier results demonstrating neurotoxicity of AE in rats. Further, these results demonstrate that the auditory discrimination task provides an objective behavioral measure of AE neurotoxicity, and thus, can serve as a valuable tool for the safety development of AE and other artemisinin antimalarial compounds.
机译：使用两项选择的离散试验，听觉辨别任务和随后的神经组织学评估了大鼠中青蒿素抗疟化合物3-arteether（AE）（25 mg / kg，i.m.）的重复给药。出现白噪声或音调+白噪声后，训练大鼠选择两种反应杠杆之一。音调强度的增加和减少分别增加和减少了可辨别性，并且不同的增强密度在响应偏差上产生了系统的变化。每天（9-12天）注射AE（n = 5）或赋形剂（n = 5）。初次注射AE不会影响行为表现。每天连续注射会导致选择准确性显着下降，选择反应时间显着增加。当观察到明显的严重毒性迹象时，处死大鼠，并且在AE处理的大鼠的梯形核中观察到明显的神经病理。在随后的实验中，连续3天注射AE 3（n = 5），5（n = 5）或7（n = 5），并再检查7天的表现。仅在接受AE的大鼠中观察到行为中断7天，并且最大程度的中断发生在AE注射完成后。组织病理学检查显示，在接受7天和5天AE方案的大鼠的梯形核，上橄榄和橡胶中以及在接受3天方案的大鼠的梯形核中均具有明显的神经病理。因此，行为中断反映但未预测神经病理学。这些结果证实并扩展了先前的结果，证实了AE对大鼠的神经毒性。此外，这些结果表明，听觉辨别任务为AE神经毒性提供了客观的行为量度，因此可以作为AE和其他青蒿素抗疟化合物安全开发的有价值的工具。

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