These data provide novel evidence that individual differences in SIP are not predictive of behavioral reactivity in animal models of anxiety and suggest an important role for the dopaminergic system in such individual differences. These findings point to SIP as a useful animal model for investigating the neurobiological basis of vulnerability to several psychopathologies in which the dopaminergic system is involved.

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The purpose of the present study was to determine the effect of two different doses of the organophosphate insecticide O,O'-diethyl-O-3,5,6-trichloro-2-pyridylphosphorothionate [chlorpyrifos (CPF)], a cholinesterase (ChE) inhibitor, in the plus-maze test of anxiety in the rat, as well as on acetylcholinesterase (AChE) activity in the brain. In a first experiment, the behavioural methodology was validated by showing the anxiolytic and anxiogenic effects of diazepam and pentylenetetrazole (PTZ), respectively. Acute exposure to CPF (166 mg/kg and 250 mg/kg, s.c.) produced significant dose-dependent inhibition (54% and 71%, respectively) of whole-brain AChE 48 hours after treatment. Neither dose produced signs of acute cholinergic toxicity at any time following treatment, as was verified by a functional observational battery. Both doses of CPF were injected 48 h before testing in the plus-maze and were shown to have anxiogenic effects as demonstrated by the significant decrease in the percentage of time spent and percentage of entries into open arms. This report thus shows clear behavioural alteration as an acute effect of an organophosphate in the absence of any classic sign of cholinergic toxicity. Our results are relevant to the understanding of both the pharmacology of anxiety and the behavioural toxicology of cholinesterase inhibitors.

Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide that has been widely used in agriculture as a pesticide. The primary mechanism of acute toxic action of OPs is initiated by acetylcholinesterase (AChE) inhibition. However, non-AChE targets have also been proposed as alternative that contributes to the acute lethal action and side effects of short or long-term exposure. Recently, we have found that a single dose of 250 mg/kg CPF produces acceleration in acquisition on schedule-induced polydipsia (SIP) procedure 6 months after its administration. Moreover, CPF animals show a higher level of impulsivity in a delay-discounting task 1 year after acute administration, and these effects are potentiated when animals are divided into high (HD) and low (LD) drinkers in SIP. In the present study, rats were injected with a subcutaneous (sc) dose of 250 mg/kg of CPF, and 10 weeks later its effect on delay-discounting task was evaluated. Consequently, these animals were evaluated based on SIP, and divided into two populations (HD and LD) according to their rates of drinking in this task. One year after OP administration, these animals were re-evaluated in a delay-discounting task. Results revealed that the CPF-administered rats prefer immediate reward and show a more impulsive choice, 10 weeks after CPF administration. Furthermore, 1 year after it administration, only animals treated with CPF that are high drinkers on SIP are more impulsive than the rest of the groups Therefore, these data suggest that some individuals are more sensitive to OP intoxication than the others, at least in terms of durability of sequelae.

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