RESUMO
Acute organophosphate (OP) poisoning induces well-known signs of toxicosis related to acetylcholinesterase (AChE) inhibition. However, the relationship between acute OP poisoning and the onset of psychiatric disorders remains unclear. Thus, we investigated behavioural and biochemical consequences of acute exposure to the OP chlorpyrifos in male rats and also the effectiveness of the antidotes atropine and pralidoxime on reversing these changes. A sub-lethal dose of commercial chlorpyrifos (20â¯mg/kg, i.p.) elicited signs of acute toxicosis during the first hours after its injection in rats. Twenty-four hours after treatment, this single dose of chlorpyrifos induced a depressive-like behaviour in the rat forced swimming test without impairing locomotor activity. At this time (24â¯h), chlorpyrifos decreased plasma butyrylcholinesterase (BChE) activity and hippocampal, striatal and prefrontal cortical AChE activity in rats. The behavioural and biochemical consequences of acute chlorpyrifos poisoning do not seem to be long lasting, since 30â¯days later they were absent. We evaluated whether these behavioural and biochemical consequences of acute chlorpyrifos treatment would be reversed by the antidotes atropine (10â¯mg/kgâ¯i.p.) and/or pralidoxime (40â¯mg/kg; i.p.) given 1â¯h after poisoning. Pralidoxime partially reactivated the AChE activity in the prefrontal cortex, but not in the hippocampus and striatum. Atropine attenuated the depressive-like behaviour induced by chlorpyrifos in rats. Our results suggest that acute chlorpyrifos poisoning induces a transient depressive-like behaviour possible related to hippocampal AChE inhibition. They suggest that treatment with atropine and pralidoxime seems to be insufficient to counteract all the effects of OP acute poisoning, at least in rats.
Assuntos
Antídotos/farmacologia , Atropina/farmacologia , Encéfalo/efeitos dos fármacos , Clorpirifos/toxicidade , Depressão/prevenção & controle , Intoxicação por Organofosfatos/prevenção & controle , Acetilcolinesterase/metabolismo , Animais , Antídotos/administração & dosagem , Atropina/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Encéfalo/enzimologia , Depressão/induzido quimicamente , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Masculino , Intoxicação por Organofosfatos/etiologia , Compostos de Pralidoxima/administração & dosagem , Compostos de Pralidoxima/farmacologia , Ratos , Ratos WistarRESUMO
Although evidence indicates that exposure to organophosphorus (OP) pesticides induces neurobehavioral disorders, little is known about the effects of OP on aggressive behaviour. Our study investigated the effects of repeated exposure to an OP pesticide, methamidophos, on the isolation-induced aggressive behaviour in mice. Forty seven male mice were individually housed for a month. Socially isolated animals were then confronted with a standard non-isolated opponent for 15 min (pre-treatment trial), and the latency and frequency of aggressive and general exploratory behaviours were recorded. Based on the presence of attack behaviour in the pre-treatment trial, mice were classified as isolation-induced aggressive and non-aggressive. All mice were then treated for 7 days with methamidophos (3.5 mg/kg/day, n = 22, intraperitoneal (i.p.)) or saline (1 mL/kg/day, control group, n = 25, i.p.), and a second trial was performed. Repeated exposure to methamidophos induced attack behaviour in non-aggressive mice. The treatment with methamidophos also decreased plasma butyrylcholinesterase and brain acetylcholinesterase activity. These results suggest that methamidophos has a pro-aggressive effect on socially isolated mice.