Comparative neurochemical and neurobehavioral effects of repeated chlorpyrifos exposures in young and adult rats

https://doi.org/10.1016/0091-3057(93)90344-SGet rights and content

Abstract

Neonatal (7 days old) rats are markedly more sensitive than adults (3 months old) to the acute toxic effects of the insecticide, chlorpyrifos (CPF). In the present study, we have compared the effects of subacute CPF exposures in these same age groups. Repeated doses of CPF (40 mg/kg, SC, every 4 days, total of 4 doses) caused extensive inhibition of cortical, hippocampal, and striatal cholinesterase (ChE) activity in adult rats at 4 (90–92%) and 14 (71–78%) days after the last treatment. Rats treated similarly during postnatal maturation (beginning on day 7) showed a much lower degree of ChE inhibition (21–60%) at these time points. Muscarinic ([3H]quinuclidinyl benzilate, QNB) receptor binding in cortex, hippocampus, and striatum was reduced in adult brain at 4 (30–43%) and 14 (22–32%) days after the final treatment, whereas receptor densities were only marginally affected (5–11% reduction) in young rats. Basal motor activity levels were not affected in either young or adult rats as a function of CPF exposure. CPF-treated adult rats exhibited higher activity levels after challenge with scopolamine (1 mg/kg, IP) at 2, 4, 6, and 8 weeks after treatment, whereas CPF exposure did not affect the motoric response to scopolamine in rats treated during postnatal maturation. These data suggest that although neonatal rats are more sensitive to acute lethal effects from high doses of CPF, adult rats exhibit more persistent neurochemical and neurobehavioral alterations following repeated, lower-level exposures.

References (26)

Cited by (105)

  • Berberine affords protection against oxidative stress and apoptotic damage in F1 generation of wistar rats following lactational exposure to chlorpyrifos

    2021, Pesticide Biochemistry and Physiology
    Citation Excerpt :

    This is in accordance with the experiments of Kondakala et al. (2017) and Ouardi et al. (2019) who reported a dose dependent effect of chlorpyrifos on AChE activity as at higher doses a significant inhibition was observed contrary to the lower doses and acute treatments. Rapid recovery of brain AChE activity following exposure is maybe due to spontaneous reactivation of the phosphorylated enzyme or de novo protein synthesis (Chakraborti et al., 1993). An important element of this study concerning cellular apoptosis focused more specifically on DNA damage-induced apoptosis.

  • Intrinsic and extrinsic factors that can modify toxicity

    2020, An Introduction to Interdisciplinary Toxicology: From Molecules to Man
  • Chemical warfare agents and the nervous system

    2020, Handbook of Toxicology of Chemical Warfare Agents
  • Oxidative Stress, Unfolded Protein Response, and Apoptosis in Developmental Toxicity

    2015, International Review of Cell and Molecular Biology
    Citation Excerpt :

    For instance, neonatal rats are more sensitive to the organophosphate, chlorpyrifos, than adults (Chakraborti et al., 1993). Chlorpyrifos has been shown to cause neurobehavioral defects following early exposure in mammals (Chakraborti et al., 1993; Chanda and Pope, 1996). It has also been linked to aberrant behavior, spinal curvature, pericardial edema, and mortality in zebrafish embryos (Kienle et al., 2009), whereas exposed frogs displayed tail flexure and decreased neuromuscular activity (Bonfanti et al., 2004).

View all citing articles on Scopus
View full text