Neonatal exposure to a type-I pyrethroid (bioallethrin) induces dose—response changes in brain muscarinic receptors and behaviour in neonatal and adult mice

doi:10.1016/0006-8993(94)91666-7

Brain Research

Volume 645, Issues 1–2, 9 May 1994, Pages 318-324

https://doi.org/10.1016/0006-8993(94)91666-7 Get rights and content

Abstract

This study shows that neonatal exposure to the insecticide bioallethrin has a dose-dependent effect on muscarinic cholinergic receptors (MAChR) in the neonatal mouse, leading to permanent changes in MAChR and in spontaneous behaviour in adult mice. Neonatal NMRI mice, given oral doses of either bioallethrin or the vehicle, once daily between the 10th and 16th postnatal day, were killed at the age of 17 days or 1 week after the spontaneous motor behaviour tests at 4 months. The MAChR were assayed in the cerebral cortex by using the antagonist quinuclidinyl benzilate ([³H]QNB) and the agonist carbachol. In the 17-day-old mice bioallethrin exposure elicited a significant dose-dependent increase in the specific [³H]QNB binding. The competition study showed that the proportion of low-affinity binding was significantly increased in the 17-day-old mice compared with controls. In the adult mouse there was a significant dose-dependent decrease in specific [³H]QNB binding. In these adult mice the behavioural variables ‘locomotion’ and ‘total activity’ showed significant (P ≤ 0.01) dose-dependent increases at all doses up to and including 0.70 mg/kg b.wt.

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We found multiple susceptible periods, spanning from the prenatal phase to age 6. Previous animal studies have suggested that both prenatal and postnatal periods may represent susceptible phases for pyrethroid neurotoxicity (Ahlbom et al. 1994; Burns et al. 2013; Eriksson and Nordberg 1990; Richardson et al. 2015; Talts et al. 1998). Multiple susceptible periods are also plausible considering the continuous brain development from in utero to adolescence (Kim et al. 2021).
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A recent study on fish erythrocytes reported genotoxicity of bioallethrin using micronuclei assay (Chaudhari and Saxena, 2016). Although neurotoxic and behavioural effects on exposure to bioallethrin are well documented (Talts et al., 1998; Ahlbom et al., 1994; Eriksson and Nordberg, 1990) there is only limited work related to toxicity in other systems. Research suggests that pyrethroids increase free radical generation which affects integrity of plasma membrane leading to cell death (Banerjee et al., 2001; Sadowska-Woda et al., 2010; Romero et al., 2012).
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Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk.
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Neonatal exposure to a type-I pyrethroid (bioallethrin) induces dose—response changes in brain muscarinic receptors and behaviour in neonatal and adult mice

Abstract

Anim. Behav.

Pestic. Biochem. Physiol.

Brain Res.

Toxicol. Lett.

Neurosci. Lett.

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Brain Res.

Neurotoxicology

Int. J. Dev. Neurochem.

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Neurosci. Lett.

Science

J. Biol. Chem.

J. Chem. Neuroanat.

Neurochem. Res.

J. Neurosci.

Brain Res.

Neurotoxicology

Life Sci.

Science

Brain Res.

Mol. Brain Res.

Nature

Behav. Brain Res.

Gen. Pharmacol.

Marble burying and spontaneous motor activity in mice: interactions over days and the effect of diazepam

Scand. J. Psychol.