Lima Carla S, Ribeiro-Carvalho Anderson, Filgueiras Cláudio C, Manhães Alex C, Meyer Armando, Abreu-Villaça Yael
Laboratório de Neurofisiologia, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Av. Prof. Manoel de Abreu 444, 5 andar - Vila Isabel, Rio de Janeiro, RJ, 20550-170, Brazil.
Neurotoxicology. 2009 May;30(3):471-8. doi: 10.1016/j.neuro.2009.01.009. Epub 2009 Feb 7.
Epidemiologic studies have suggested that organophosphate exposure is associated with an increased risk of depression and suicide. Considering that the neurobiological basis of this association is not well understood, in the present study we evaluated the depressive-like behavior of Swiss mice subchronically exposed to the organophosphate methamidophos at adulthood. From postnatal days 60 to 89 (PN60-PN89), one of two concentrations of methamidophos [higher dose (HiD): 5.25 microg/ml; lower dose (LoD): 1.31 microg/ml] or vehicle was administered in the drinking water. Immobile behavior, an animal model of depressive behavior, was assessed in the forced swimming and tail suspension tests either during (PN88) or after (PN99) the exposure period. On the subsequent day (PN89 or PN100), the Rota-rod and endurance swimming tests were used to evaluate motor performance. Brain acetylcholinesterase activity was quantified. During exposure, the LoD group presented increased immobility in the tail suspension test when compared to controls. The HiD group presented increased immobility in the forced swimming test when compared to LoD and control groups, an effect that emerged after cessation of exposure. There were no motor performance alterations. During exposure, acetylcholinesterase activity was inhibited in the HiD (43%) and LoD (15%) groups. After exposure, enzyme activity was reduced (25%) only in the HiD group. There were no signs of systemic toxicity. There were no correlations between acetylcholinesterase activity and behavioral measures. Our results indicate that methamidophos at doses below the threshold for systemic toxicity induces depressive-like behavior in adult mice.
流行病学研究表明，接触有机磷与抑郁症和自杀风险增加有关。鉴于这种关联的神经生物学基础尚未完全明确，在本研究中，我们评估了成年期亚慢性接触有机磷甲胺磷的瑞士小鼠的抑郁样行为。从出生后第60天至89天（PN60 - PN89），在饮用水中给予两种浓度之一的甲胺磷[高剂量（HiD）：5.25微克/毫升；低剂量（LoD）：1.31微克/毫升]或溶剂。在暴露期间（PN88）或暴露后（PN99），通过强迫游泳和悬尾试验评估作为抑郁行为动物模型的不动行为。在随后的一天（PN89或PN100），使用转棒试验和耐力游泳试验评估运动性能。对脑乙酰胆碱酯酶活性进行定量分析。在暴露期间，与对照组相比，LoD组在悬尾试验中的不动时间增加。与LoD组和对照组相比，HiD组在强迫游泳试验中的不动时间增加，这种效应在暴露停止后出现。未观察到运动性能改变。在暴露期间，HiD组（43%）和LoD组（15%）的乙酰胆碱酯酶活性受到抑制。暴露后，仅HiD组的酶活性降低（25%）。未出现全身毒性迹象。乙酰胆碱酯酶活性与行为指标之间无相关性。我们的结果表明，低于全身毒性阈值剂量的甲胺磷可诱导成年小鼠出现抑郁样行为。
