Abstract
Following reports of emotional psychopathology in children and adults exposed to organophosphates, the effects of postnatal chlorpyrifos (CPF) on fear-conditioning and depression-like behaviors were tested in adult mice. Concomitant changes in expression of mRNA for synaptic and soluble splice variants of acetylcholinesterase (AChE) were examined in mouse pups and adults of the Balb/C and C57Bl/6 (B6) strains, which differ in their behavioral and hormonal stress response. Mice were injected subcutaneously with 1 mg/kg CPF on postnatal days 4–10 and tested as adults for conditioned fear, sucrose preference, and forced swim. Acetylcholinesterase activity was assessed in the brains of pups on the first and last day of treatment. Expression of soluble and synaptic AChE mRNA was assessed in brains of treated pups and fear-conditioned adults using real-time PCR. Adult Balb/C mice exposed postnatally to CPF showed exacerbated fear-conditioning and impaired active avoidance. Adult B6 mice exposed postnatally to CPF showed a more specific fear response to tones and less freezing in the inter-tone intervals, in contrast to the vehicle-pretreated mice. Chlorpyrifos also attenuated sweet preference and enhanced climbing in the forced swim test. Chlorpyrifos-treated mice had increased expression of both synaptic and readthrough AChE transcripts in the hippocampus of Balb/C mice and decreased expression in the amygdala following fear-conditioning. In conclusion, postnatal CPF had long-term effects on fear and depression, as well as on expression of AChE mRNA. These changes may be related to alteration in the interaction between hippocampus and amygdala in regulating negative emotions.
Highlights
Extensive use of organophosphate pesticides (OPs), including chlorpyrifos (CPF), in agriculture is a subject of concern because of potential neurodevelopmental deficits following low level exposure.Emotional pathology following postnatal chlorpyrifosExposure to OPs is ubiquitous from gestation to adulthood
A 3-Way repeated measures ANOVA (RMANOVA) conducted between Treatment (NT, Vehicle, CPF), Strain (Balb/C; Balb/C and C57Bl/6 (B6)), and Day (PND-4 to -10) as a repeated measure, revealed the expected significant main effect of Day, F(6, 792) = 634.8; p < 0.00001, indicating growth
In adult mice there were no significant difference in groups pretreated with CPF or vehicle, there was a significant effect of Strain, F(1, 83) = 28.94, p = 0.000001, indicating that Balb/C mice were significantly heavier than B6 mice
Summary
Extensive use of organophosphate pesticides (OPs), including chlorpyrifos (CPF), in agriculture is a subject of concern because of potential neurodevelopmental deficits following low level exposure.Emotional pathology following postnatal chlorpyrifosExposure to OPs is ubiquitous from gestation to adulthood. Longitudinal studies in the USA indicated an association between gestational exposure to OPs and lower scores on IQ tests, attention deficits, impaired neurocognitive functions (Rauh et al, 2006, 2011; Marks et al, 2010; Bouchard et al, 2011; Engel et al, 2011), altered frontal lobe structure (Rauh et al, 2012), and increased signs of pervasive developmental disorder (PDD) and social dysfunction in specific populations of children (Engel et al, 2007; Eskenazi et al, 2007; Furlong et al, 2014). A reduction in the EPM anxiety assay was reported following perinatal exposure to CPF (Aldridge et al, 2005a; Ricceri et al, 2006) or diazinon (Roegge et al, 2008) but increased anxiety was reported in female mice after extended gestational and postnatal CPF exposure (Braquenier et al, 2010). In this study we focused on cued conditioned fear responses which are used to model phobic and trauma-related psychopathology
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