Effects of chlorpyrifos in the plus-maze model of anxiety

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.