EFEITOS IDADE-DEPENDENTES DA INTOXICAÇÃO AGUDA PELO ORGANOFOSFORADO TRIAZOFÓS SOBRE COMPORTAMENTOS RELACIONADOS À ANSIEDADE E DEPRESSÃO EM RATOS

Abstract

Organophosphate compounds (OP) are acetylcholinesterase (AChE) inhibitors widely used in agriculture for pest control, especially in developing countries. Exposure to OP can increase the risk of developing depression, anxiety and cognitive disorders. The behavioral consequences of acute triazophos (TZP) intoxication, a moderately toxic OP, in tests related to depression and anxiety have not yet been investigated. OP tend to affect juvenile animals to a greater extent than adults. Therefore, our objective was to investigate whether acute exposure to TZP would induce different profiles of behavioral changes related to anxiety and depression in juvenile and adult rats. For this, juvenile (28 days) and adult (8 weeks) male Wistar rats were acutely intoxicated (ip) with sublethal doses of a commercial formulation of TZP (doses of 3.75, 7.5 and 15 mg/kg for juveniles and, 7.5, 15 and 30 mg/kg for adults) or treated with saline solution (control group). The animals were tested 24 hours after intoxication in an open field (OF) and in an elevated plus maze (EPM) to assess locomotor activity and anxious behaviors. We also evaluated the activity of AChE in the hippocampus and cortex of these animals. An independent group of animals was subjected to the forced swim test (FST) 24 h, 8, 15 and 22 days after intoxication to assess persistent behavioral effects. In adult rats, TZP 7.5 mg/kg increased the percentage of entries, while TZP 15 mg/kg decreased the percentage of time spent in the open arms of the EPM, suggesting anxiolytic and anxiogenic effects, respectively. In juvenile animals, only TZP 3.75 mg/kg promoted anxiogenic effect. TZP impaired locomotion in the OF in juveniles at the highest dose. TZP decreased the percentage of OF center entries at the highest dose in both juvenile and adult rats. At the highest doses, TZP inhibited hippocampal and cortical AChE in both juvenile and adult rats. All doses of TZP increased immobility and reduced swimming frequency in the FST 24 h after intoxication, suggesting a depressive-like effect. In juvenile rats, TZP 15 mg/kg also decreases climbing frequency. The depressive-like effect of TZP persisted for up to 15 days in juvenile animals treated with TZP 7.5 and 15 mg/kg and for 22 days in adult animals treated with TZP 7.5 and 30 mg/kg. Our results demonstrate that juvenile and adult animals present different patterns of behavioral changes after a single TZP exposure, suggesting that acute intoxication is sufficient to cause short- and long-term damage Additionally, AChE inhibition seems not to be the only mechanism underlying these behavioral effects. Our results point to the need for monitoring the mental health of patients who survive an acute OP intoxication.