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The molecular and behavioral effects of the developmental exposure to low doses of Chlorpyrifos (CPF) have been intensively studied in young (neonates and adolescents), and adult animals. However, no study examined influences of developmental CPF exposure in older adult or geriatric rats. This is relevant as such ages are generally linked to cognitive decline and the onset of specific neurodegenerative disorders, some of them previously associated with CPF exposure in both preclinical and human studies. 1 mg/kg/mL of CPF was orally administered to both male and female Wistar rats from Postnatal day 10 to 15. Animals' spatial memory, learning, compulsivity, motricity, and anxiety were analyzed with Morris Water Maze (15-16 months of age) and the Plus-maze (at 18 months of age). Results showed that postnatal CPF exposure did not alter either spatial memory, compulsive-like behaviors, or anxiety levels in late-adult rats. However, CPF exposed rats were hyposensitive to brief disruptions (Probe stage) following the learning phase and showed a general decrease in locomotor activity in both paradigms. These data are relevant as it is the first time that developmental exposure to CPF has been studied at such a late age, observing important effects in locomotor activity that could be linked to specific pathologies previously associated with CPF effects in people. Future studies should extend these findings to other behaviors and molecular outcomes.

Exposure to pesticides has been linked to an increased vulnerability to neurodegenerative diseases. In order to study whether the exposure to the organophosphate chlorpyrifos renders the brain prone to amyloid-beta peptide deposition and accelerates its neuropathological and behavioural effects, Wistar rats were injected a single subcutaneous dose of chlorpyrifos (250 mg/kg) and subsequently infused with Aβ(1–42) peptide (i.c.v.) for 15 days. No effects of either treatment were noted in the classic water maze test. The animals infused with Aβ peptide showed worse performance when the platform was both hidden and moved from trial to trial. Both groups showed worse performance when the platform was visible and moved from trial to trial. No amyloid deposition was observed in hippocampus or cerebral cortex after the infusion period, although microtubule-associated protein 1A (MAP1A) immunoreactivity was significantly reduced in hippocampus and prefrontal cortex, whereas chlorpyrifos exposure produced a significant reduction of microtubule-associated protein 2 (MAP2) in the prefrontal cortex. Therefore, behavioural deficits could be related to a loss of dendrite and spine processes in these brain regions.

Little is known about the long-term effects of chronic exposure to low-level organophosphate (OP) pesticides, and the role of neurotransmitter systems, other than the cholinergic system, in mediating OP neurotoxicity. In this study, rats were administered 5 mg/kg/day of chlorpyrifos (CPF) for 6 months commencing at 3-months-of-age. The animals were examined 7 months later (at 16-months-of-age) for spatial learning and memory in the Morris water maze (MWM) and locomotor activity. In addition, we assessed the chronic effects of CPF on glutamatergic and gamma-aminobutyric acid (GABAergic) function using pharmacological challenges with dizocilpine (MK801) and diazepam. Impaired performance related to altered search patterns, including thigmotaxis and long-term spatial memory was noted in the MWM in animals exposed to CPF, pointing to dietary CPF-induced behavioral disturbances, such as anxiety. Twenty-four hours after the 31st session of repeated acquisition task, 0.1 mg/kg MK801, an N-methyl-. d-aspartate (NMDA) antagonist was intraperitoneally (i.p.) injected for 4 consecutive days. Decreased latencies in the MWM in the control group were noted after two sessions with MK801 treatment. Once the MWM assessment was completed, animals were administered 0.1 or 0.2 mg/kg of MK801 and 1 or 3 mg/kg of diazepam i.p., and tested for locomotor activity. Both groups, the CPF dietary and control, displayed analogous performance in motor activity. In conclusion, our data point to a connection between the long-term spatial memory, thigmotaxic response and CPF long after the exposure ended.