Time course of biochemical and behavioural effects of a single high dose of chlorpyrifos.

The purpose the present study was to determine if tolerance is developed to all behavioural effects produced by a single high dose of chlorpyrifos (CPF). For this, the study was divided in two phases; in the first phase, we studied the time course of the effects produced by treatment with a high dose of CPF (250 mg/kg s.c.) on rat locomotor activity and anxiety behaviours recorded on an open-field, as well as on AChE inhibition. Results showed that CPF produced a maximum inhibition of AChE (72% of inhibition) 2 days after its administration, exhibiting a partial recovery of its activity by day 30 (55% of inhibition). On locomotor activity CPF produced a biphasic effect; a reduction only on day 2, and an increase on day 30. An anxiolytic-like effect was only observed within 2 and 5 days after CPF treatment. These results indicate that the tolerance has been developed to the behavioural effects produced by s.c. administration of CPF, but with a different time course. In the second phase, since disturbances in cholinergic system might trigger dopaminergic dysfunctions, we tested the locomotor activity following challenge with amphetamine (1mg/kg i.p.) at 11 and 30 days after CPF treatment. Data obtained showed that amphetamine produced an increase in total distances and rearing in vehicle and CPF groups on days 11 and 30. However, CPF group exhibited lower increase relative to vehicle group in both days. This effect is independent of the percentage of AChE inhibition and therefore, of change in the cholinergic system. Data are discussed under the light of the adaptative mechanisms underlying the recovery of the cholinergic overstimulation after s.c. exposure to high doses of CPF.