Acute intoxication by organophosphorus anticholinesterases (OPs) has been associated with depression and other neuropsychiatric disorders. We previously reported that adult male rats treated with diisopropylfluorophosphate (2.5 mg/kg, sc) showed acute cholinergic signs followed by changes (increased immobility/decreased swimming) in the forced swim test (a measure of behavioral despair) for at least one month. This study was conducted to evaluate the further persistence of changes in the forced swim test out to 4 months and to compare responses in a sucrose preference test, a measure of anhedonia. Adult male rats were treated with vehicle (peanut oil, 1 mL/kg, sc) or DFP (2.0, 2.25 or 2.5 mg/kg) followed by sacrifice 4 h later for measurement of OP-sensitive serine hydrolases (cholinesterase [ChE], fatty acid amide hydrolase [FAAH], and monoacylglycerol lipase [MAGL]) in hippocampus. Additional rats were treated similarly and evaluated for functional signs of acute toxicity from 30 min to 6 days, and then motor activity, forced swim behavior and sucrose preference at approximately 1 week, 1 month and 4 months after dosing. All dosages of DFP elicited serine hydrolase inhibition (ChE, 92–96 %; FAAH, 46–63 %; MAGL, 26–33 %). Body weight was reduced in all DFP-treated groups during the first two weeks, and lethality was noted with the higher dosages. Involuntary movements were elicited in all DFP treatment groups during the first week, but both time of onset and rate of recovery were dose-related. There was a significant reduction in ambulation at one week after the highest dosage (2.5 mg/kg), but no other significant locomotor changes were noted. Immobility was increased and swimming was decreased in the forced swim test at all three time-points by 2.25 mg/kg DFP, and at 2 of 3 time-points by the other dosages. While length of water deprivation and time after DFP dosing affected sucrose preference, DFP treatment had no main effect. We conclude that the forced swim test (a measure of behavioral despair/coping mechanism for inescapable stress) is a robust and persistent neurobehavioral consequence of acute DFP intoxication while sucrose preference, a measure of anhedonia and a common symptom of major clinical depression, is not affected.

有机磷抗胆碱酯酶 (OP) 的急性中毒与抑郁症和其他神经精神疾病有关。我们之前曾报道过，用二异丙基氟磷酸盐（2.5 毫克/千克，皮下）治疗的成年雄性大鼠在强迫游泳测试（一种行为绝望的测量）中表现出急性胆碱能迹象，随后出现变化（增加不动/减少游泳）至少一个月。进行这项研究是为了评估强迫游泳测试中变化的进一步持续性长达 4 个月，并比较蔗糖偏好测试中的反应，这是一种衡量快感缺乏的方法。成年雄性大鼠用载体（花生油，1 mL/kg，sc）或 DFP（2.0、2.25 或 2.5 mg/kg）治疗，4 小时后处死以测量 OP 敏感的丝氨酸水解酶（胆碱酯酶 [ChE]，脂肪酸酰胺水解酶 [FAAH]，和海马体中的单酰基甘油脂肪酶 [MAGL])。对另外的大鼠进行类似处理，并在给药后约 1 周、1 个月和 4 个月评估 30 分钟至 6 天的急性毒性的功能体征，然后评估运动活动、强迫游泳行为和蔗糖偏好。所有剂量的 DFP 都引起丝氨酸水解酶抑制（ChE，92–96 %；FAAH，46–63 %；MAGL，26–33 %）。在前两周，所有 DFP 治疗组的体重都降低了，并且在较高剂量下观察到了致死率。在第一周内，所有 DFP 治疗组都引发了不自主运动，但发病时间和恢复速度均与剂量相关。在最高剂量 (2.5 mg/kg) 后一周，行走显着减少，但没有注意到其他显着的运动变化。在强迫游泳测试中，2.25 mg/kg DFP 在所有三个时间点增加了不动，而在三个时间点中的 2 个时间点使用其他剂量减少了游泳。虽然断水时间和 DFP 给药后的时间会影响蔗糖偏好，但 DFP 处理没有主要影响。我们得出结论，强迫游泳测试（一种对不可避免的压力的行为绝望/应对机制的测量）是急性 DFP 中毒的一种强大而持久的神经行为后果，而蔗糖偏好，一种快感缺乏的测量方法和主要临床抑郁症的常见症状，不是做作的。