Background

Phosalone (Pln) is an organophosphorus pesticide acetylcholinesterase (AChE) inhibitor. Blockade of AChE amplifies ACh signaling that is related to depressive symptoms. The effects of Pln exposure were evaluated on depressive behavior in mice and the involvement of muscarinic ACh receptor (MAChR) was assessed.

Material and methods

After measuring total activity in the locomotor test the immobility time during the forced swimming test (FST) in male mice was evaluated as an index of depression. Pln single dose was administered by gavage feeding and examined after 3 h (day1) and on day 7 for evaluating delayed toxicity. In separate groups Pln was administered for 5 consecutive days and examined on day 6 also after one-week delay on day12.

Results

While there were only marginal differences in the locomotor tests. Immobility time during the FST significantly increased on day1 by Pln 6, 12, 40 mg/kg (185 ± 17 s, 186 ± 9 s, 172.0 ± 7 s respectively) compared with control animals (149 ± 8 s, p < 0.01), immobility time was higher than control on day 6 after multiple exposures to Pln (0.6, 6, 12, 20 mg/kg 190 ± 20s, 210 ± 4 s, 196 ± 10s, 204 ± 9 respectively, vs control 153 ± 7 p < 0.001). The immobility time remained high following a week of relapse. The co-administration of Pln with scopolamine (Scp) a MAChR antagonist reduced immobility time (141 ± 10s vs Pln 186 ± 9 s, p < 0.01).

Conclusion

Single exposure to Pln induced depressive-like effects that were reversed by Scp, indicating that MAChR stimulation may be involved. While cumulative exposures caused more pronounced changes in depressive behavior that remained after a week from the last exposure.

中文翻译：

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AChR 对 Phosalone 暴露后小鼠的抑郁样行为负有部分责任

背景

Phosalone (Pln) 是一种有机磷农药乙酰胆碱酯酶 (AChE) 抑制剂。AChE 的阻断会放大与抑郁症状相关的 ACh 信号。评估了 Pln 暴露对小鼠抑郁行为的影响，并评估了毒蕈碱乙酰胆碱受体 (MAChR) 的参与情况。

材料与方法

在运动测试中测量总活动量后，雄性小鼠强迫游泳测试 (FST) 期间的不动时间被评估为抑郁指数。Pln 单剂量通过管饲法给药，并在 3 小时（第 1 天）和第 7 天后检查以评估延迟毒性。在不同的组中，连续 5 天施用 Pln，并在第 12 天延迟一周后在第 6 天进行检查。

结果

虽然在运动测试中只有微小的差异。与对照动物 (149 ± 8 s, p  < 0.01)相比，FST 期间的不动时间在第 1 天显着增加 Pln 6、12、40 mg/kg（分别为 185 ± 17 s、186 ± 9 s、172.0 ± 7 s ） , 多次暴露于 Pln 后第 6 天的不动时间高于对照（0.6、6、12、20 mg/kg 190 ± 20 秒、210 ± 4 秒、196 ± 10 秒、204 ± 9，对比对照 153 ± 7 p  < 0.001)。在复发一周后，不动时间仍然很长。Pln 与东莨菪碱 (Scp) 一种 MAChR 拮抗剂的共同给药减少了不动时间（141 ± 10 秒与 Pln 186 ± 9 秒，p  < 0.01）。

结论

单次暴露于 Pln 诱导的抑郁样效应被 Scp 逆转，表明可能涉及 MAChR 刺激。虽然累积暴露导致抑郁行为发生更明显的变化，但在最后一次暴露一周后仍然存在。