Long term compulsivity on the 5-choice serial reaction time task after acute Chlorpyrifos exposure

Abstract

Pesticide exposure has been associated with neuropsychological and psychiatric impairments and neurodegenerative disorders. Pesticide exposure commonly causes a deficit in inhibitory control behaviours. In the present study, we investigated whether acute exposure to organophosphate (OP) chlorpyrifos (CPF) is related to long-term lack of inhibitory control; we also examined the possible neurochemical basis of this association. Lister Hooded rats were exposed to an acute dose of CPF (250 mg/kg). Seven months later, we tested inhibitory control with the 5-choice serial reaction time task (5-CSRTT). We manipulated the baseline conditions of this task and also systemically pre-administered d-amphetamine, quinpirole, dizocilpine (MK-801) or ketanserin. We also analysed the post-mortem baseline levels of monoamines and amino acids in different brain regions. On the 5-CSRT task, CPF-exposed rats showed elevated perseverative responses that persisted across manipulation of baseline conditions of the task and under most of the pharmacological challenges tested. Only D-amphetamine induced a dose-dependent amelioration of the increased perseverative responses in the CPF group. The CPF group also exhibited increased levels of dopamine metabolism in the hippocampus and decreased levels of gamma-aminobutyric acid (GABA) and glutamate in the striatum compared to the vehicle group. These findings suggest that CPF induced a long-term compulsivity that was apparent in the 5-CSRT task and associated with changes in monoaminergic and amino acid brain systems of inhibitory control function. Exposure to high doses of OP should be taken into account in studies of environmental causes for neurodegenerative, neuropsychological and neuropsychiatric disorders.