ArticleChemico-biological interactions2016
Mechanism for the acute effects of organophosphate pesticides on the adult 5-HT system.
Article in Chemico-biological interactions, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 45 citations in OpenAlex.
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- Neuroprotective and antioxidant effects of3 Biotech · 2025Article
- LC-MS/MS-Profiling of Human Serum Unveils Significant Increase in Neuroinflammation and Carcinogenesis Following Chronic Organophosphate Exposure.Journal of proteome research · 2025Article
- Protective effect of quercetin liposome on acute low dose diazinon-induced oxidative stress and neurobehavioral disorders by affecting serotonin metabolite in mature male rats.Veterinary research forum : an international quarterly journal · 2025Article
- Neuroprotective Effect of WhiteFoods (Basel, Switzerland) · 2023Article
- Use of computational toxicology tools to predictCurrent research in toxicology · 2022Article
- A Fluidics-Based Biosensor to Detect and Characterize Inhibition Patterns of Organophosphate to Acetylcholinesterase in Food Materials.Micromachines · 2021Article
- Therapeutic Potential of Dihydropyridine Calcium Channel Blockers on Oxidative Injury Caused by Organophosphates in Cortex and Cerebellum: An In Vivo Study.Indian journal of clinical biochemistry : IJCB · 2020Article
- Pulmonary thrombosis in acute organophosphate poisoning-Case report and literature overview of prothrombotic preconditioning in organophosphate toxicity.Toxicology reports · 2019Article
- Protective effect of some plant oils on diazinon induced hepatorenal toxicity in male rats.Saudi journal of biological sciences · 2017Article
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10 authors at 1 institution in 1 country.
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Abstract
The neurotransmitter serotonin (5-HT) is involved in mood disorder aetiology and it has been reported that (organophosphate) OP exposure affects 5-HT turnover. The aim of this study was to elucidate the mechanism underlying OP effects on the adult 5-HT system. First, acute in vivo administration of the OP diazinon (0, 1.3, 13 or 39 mg/kg i.p.) to male Hooded Lister rats inhibited the activity of the cholinergic enzyme acetylcholinesterase in blood and in the hippocampus, dorsal raphe nucleus (DRN), striatum and prefrontal cortex. Diazinon-induced cholinesterase inhibition was greatest in the DRN, the brain's major source of 5-HT neurones. Second, acute in vivo diazinon exposure (0 or 39 mg/kg i.p.) increased the basal firing rate of DRN neurones measured ex vivo in brain slices. The excitatory responses of DRN neurones to α1-adrenoceptor or AMPA/kainate receptor activation were not affected by in vivo diazinon exposure but the inhibitory response to 5-HT was attenuated, indicating 5-HT1A autoreceptor down-regulation. Finally, direct application of the diazinon metabolite diazinon oxon to naive rat brain slices increased the firing rate of DRN 5-HT neurones, as did chlorpyrifos-oxon, indicating the effect was not unique to diazinon. The oxon-induced augmentation of firing was blocked by the nicotinic acetylcholine receptor antagonist mecamylamine and the AMPA/kainate glutamate receptor antagonist DNQX. Together these data indicate that 1) acute OP exposure inhibits DRN cholinesterase, leading to acetylcholine accumulation, 2) the acetylcholine activates nicotinic receptors on 5-HT neurones and also on glutamatergic neurones, thus releasing glutamate and activating 5-HT neuronal AMPA/kainate receptors 3) the increase in 5-HT neuronal activity, and resulting 5-HT release, may lead to 5-HT1A autoreceptor down-regulation. This mechanism may be involved in the reported increase in risk of developing anxiety and depression following occupational OP exposure.
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