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.

Acute high dose of chlorpyrifos alters performance of rats in the elevated plus-maze and the elevated T-maze.

Chlorpyrifos (CPF) is a broad spectrum organophosphate (OP) pesticide widely used in agriculture, industry and household. Several animal studies indicate emotional disturbances after CPF exposure, although the results are sometimes puzzling. Thus, both anxiolytic and anxiogenic effects of CPF have been reported in different animal models of anxiety [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92; Sánchez-Amate MC, Dávila E, Cañadas F, Flores P, Sánchez-Santed F. Chlorpyrifos shares stimulus properties with pentilenetetrazol as evaluated by and operant drug discrimination task. Neurotoxicology 2002;23:795-803; López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7]. On the other hand, other behavioural effects of CPF are time-dependent [López-Crespo G, Carvajal F, Flores P, Sánchez-Santed F, Sánchez-Amate MC. Time-course of biochemical and behavioural effects of a single high dose of chlorpyrifos. Neurotoxicology 2007;28:541-7], raising the question that the effects of CPF could be task and post-administration time dependent. To test this hypothesis, three groups of rats were treated with a single high dose of CPF (250 mg/kg); one of the groups was tested on day 5 on the elevated plus-maze, to complete our previous study on day 2 [Sánchez-Amate MC, Flores P, Sánchez-Santed F. Effects of chlorpyrifos in the plus-maze model of anxiety. Behav Pharmacol 2001;12:285-92]. The remaining groups were tested on the elevated T-maze on days 2 and 5. CPF produced an increased open arm activity on the elevated plus-maze on day 5, an increased escape latency on the elevated T-maze on day 2 and an impaired inhibitory avoidance on day 5. Data are discussed taking together all studies carried out in our laboratory, confirming that CPF effects on emotional behaviour are dependent on both task contingencies and post-administration time.