Vulnerability of long-term neurotoxicity of chlorpyrifos: effect on schedule-induced polydipsia and a delay discounting task.
BACKGROUND
Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide that has been widely used in extensive agriculture as a pesticide. The primary mechanism of acute toxic action of OPs is inhibition of acetylcholinesterase (AChE). However, targets other than AChE have been proposed to contribute to the acute lethal action and side effects of short- or long-term exposure to these compounds. Bekkedal et al. (Sci Total Environ 274:119-123;2001) showed that chronic administration of the OP trimethylolpropane phosphate (TMPP) reduces the number of schedule-induced polydipsia (SIP) sessions necessary to induce asymptotic drinking level.


METHODS
In the present work, rats were injected with 250 mg/kg CPF and 6 months later, its effect on schedule-induced polydipsia was evaluated. In addition, after stable levels of SIP, a pharmacological study was carried out to determine the implication of other systems in the long-term effects of OPs. Finally, these animals were evaluated in a delay discounting task, as a measure of impulsivity.


RESULTS
Results indicate that the CPF group gives more licks to obtain the same amount of water than control rats (VHC). Moreover, the administration of diazepam produces an increased water intake in the CPF without any observable effect in VHC rats. Data of the delay discounting task show that CPF rats prefer an immediate reward and show a major impulsive choice.


CONCLUSIONS
Taken together, our data confirm and extend the long-term behavioral effects of subcutaneous administration of CPF and point to a role for other systems that, besides AChE inhibition, contribute to the long-term neurotoxicity of CPF.
Cardona
D
D
Departamento de Neurociencia y Ciencias de la Salud, Universidad de Almería, La Cañada, Almería, 04120, Spain. dcardona@ual.es
López-Grancha
M
M
López-Crespo
G
G
Nieto-Escamez
F
F
Sánchez-Santed
F
F
Flores
P
P
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004390:Chlorpyrifos / Q000633:toxicity*; D018679:Cholinergic Agonists / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004327:Drinking Behavior / Q000187:drug effects*; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D007175:Impulsive Behavior; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000523:psychology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D013997:Time Factors
D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D018756:GABA Antagonists; D018757:GABA Modulators; D007306:Insecticides; D000110:Acetylcholinesterase; D004390:Chlorpyrifos