Behavioral and biochemical effects of neonicotinoid thiamethoxam on the cholinergic system in rats

Departamento de Fisiologia, Centro de Ciências Biológicas, Universidade Federal do Pará, Belém-PA, Brazil.
Ecotoxicology and Environmental Safety (Impact Factor: 2.76). 06/2009; 73(1):101-7. DOI: 10.1016/j.ecoenv.2009.04.021
Source: PubMed


Thiamethoxam is a neonicotinoid insecticide, a group of pesticides that acts selectively on insect nicotinic acetylcholine receptors (nAChRs), with only a little action on mammalian nAChRs. Nevertheless, the selectivity of neonicotinoids for the insect nAChRs may change when these substances are metabolized. Therefore, we aimed to determine the potential effects of thiamethoxam on mammalian brain, testing the performance in the open field and elevated plus-maze of rats exposed to this insecticide and, in order to establish the neurochemical endpoints, we measured the acetylcholinesterase activity in different brain regions (hippocampus, striatum and cortex) and the high-affinity choline uptake (HACU) in synaptosomes from rat hippocampus. Treated animals received thiamethoxam (25, 50 or 100mg/kg) for 7 consecutive days. The results showed that treatment with thiamethoxam induced an increase in the anxiety behavior at two doses (50 or 100mg/kg). Moreover, there was a significant decrease in both HACU and acetylcholinesterase activity. Our hypothesis is that thiamethoxam (or its metabolites) could be acting on the central rats nAChRs. This would produce an alteration on the cholinergic transmission, modulating the anxiety behavior, acetylcholinesterase levels and HACU.

Download full-text


Available from: Maxwell Santana, Jan 25, 2015
    • "It also caused the impairment of olfactory learning and abnormal responsiveness to water in Apis mellifera[20] and blocked the normal process of oviposition and feeding in brown cocoa mired.[21] Recently, Rodrigues et al.,[22] has reported a significant increase in high affinity choline uptake and acetylcholine activity in the brain of rats exposed to the thiamethoxam. In one of our recent studies to evaluate the genotoxicity of LC20 of cypermethrin on ITS1 and 2 of Culex quinquefasciatus, a significant increase in the incidence of induced nucleotide mutations were observed in the form of deletion, insertion and substitution of bases at several loci along the amplified sequences.[3] "
    [Show abstract] [Hide abstract]
    ABSTRACT: The present article deals with the polymerase chain reaction (PCR)-based genotoxicity evaluation of neonicotinoid pesticides, imidacloprid and thiamethoxam, by using the genome of a mosquito Anopheles stephensi taken as an experimental model. After treatment of the second instar larvae with LC(20) of the pesticides for 24 h, the induced nucleotide sequence variations in the internal transcribed spacer 2 (ITS2) of freshly hatched unfed control and treated individuals was studied from the sequence alignment data and the mutations in the form of insertion, deletion and substitution of bases were recorded. Measurable differences, indicative of the genetic damage due to imidacloprid and thiamethoxam were observed when ITS2 sequences of control and treated individuals were compared. It was found that imidacloprid-treated individual had 8 deletions, 29 insertions, 18 transitions and 33 transversions, whereas thiamethoxam-treated individual had 10 deletions, 8 insertions, 47 transitions and 68 transversions.
    05/2012; 19(2):201-6. DOI:10.4103/0971-6580.97223
  • Source
    • "The insecticidal activity of neonicotinoids is caused by their modes of action on nicotinic acetylcholine receptors (nAChRs). Neonicotinoids are active as acetylcholine agonists at the postsynaptic insect nAChRs with much higher affinity, and the toxicity of these compounds plays a major role in pest control (Muccio et al., 2006; Rodrigues et al., 2010; Tomizawa & Casida, 2005; Van Scoy et al., 2010). However, the neurotoxicity of these compounds also affects useful insects such as bees (EFSA, 2010), and this non-targeted property may constitute a fatal flaw of the neonicotinoid insecticides. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A determination method for clothianidin and its metabolites (MNG, TMG, TZMU, and TZNG) in crown daisy, sedum, and amaranth grown under greenhouse conditions has been developed. The target compounds were identified and quantitatively determined using liquid chromatography coupled to tandem mass spectrometry. The matrix-matched calibration curves, used for quantification of the field-incurred analyte residues, were linear with coefficients of determination (r2) exceeding 0.99. The matrix effects ranged from −61.4 ± 3.6 to 328.3 ± 26.9 in three different crops. The limits of detection and quantitation were in the ranges of 0.01–0.04 and 0.04–0.16 mg/kg, respectively. The mean recoveries of the analytes ranged between 71.7% and 120.3%. The validated method developed herein was successively applied for the determination of clothianidin and its four metabolites in field-incurred samples. The parent compound, clothianidin, was identified as the main residue and the metabolite residues were variable in the treated crown daisy, sedum, and amaranth samples.
    Food Chemistry 04/2012; 131(4):1546–1551. DOI:10.1016/j.foodchem.2011.09.134 · 3.39 Impact Factor
  • Source
    • "Exposure to IMI in utero causes decreased sensorimotor performance and increased expression of glial fibrillary acidic protein (GFAP) in the motor cortex and hippocampus of neonatal rats [10]. Furthermore, it has been reported that the neonicotinoids thiamethoxam and clothianidin induce dopamine release in the rat striatum via nAChRs [11] and that thiamethoxam alters behavioral and biochemical processes related to the rat cholinergic systems [12]. Recently, IMI and clothianidin have been reported to agonize human α4β2 nAChR subtypes [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Acetamiprid (ACE) and imidacloprid (IMI) belong to a new, widely used class of pesticide, the neonicotinoids. With similar chemical structures to nicotine, neonicotinoids also share agonist activity at nicotinic acetylcholine receptors (nAChRs). Although their toxicities against insects are well established, their precise effects on mammalian nAChRs remain to be elucidated. Because of the importance of nAChRs for mammalian brain function, especially brain development, detailed investigation of the neonicotinoids is needed to protect the health of human children. We aimed to determine the effects of neonicotinoids on the nAChRs of developing mammalian neurons and compare their effects with nicotine, a neurotoxin of brain development. Primary cultures of cerebellar neurons from neonatal rats allow for examinations of the developmental neurotoxicity of chemicals because the various stages of neurodevelopment-including proliferation, migration, differentiation, and morphological and functional maturation-can be observed in vitro. Using these cultures, an excitatory Ca(2+)-influx assay was employed as an indicator of neural physiological activity. Significant excitatory Ca(2+) influxes were evoked by ACE, IMI, and nicotine at concentrations greater than 1 µM in small neurons in cerebellar cultures that expressed the mRNA of the α3, α4, and α7 nAChR subunits. The firing patterns, proportion of excited neurons, and peak excitatory Ca(2+) influxes induced by ACE and IMI showed differences from those induced by nicotine. However, ACE and IMI had greater effects on mammalian neurons than those previously reported in binding assay studies. Furthermore, the effects of the neonicotinoids were significantly inhibited by the nAChR antagonists mecamylamine, α-bungarotoxin, and dihydro-β-erythroidine. This study is the first to show that ACE, IMI, and nicotine exert similar excitatory effects on mammalian nAChRs at concentrations greater than 1 µM. Therefore, the neonicotinoids may adversely affect human health, especially the developing brain.
    PLoS ONE 02/2012; 7(2):e32432. DOI:10.1371/journal.pone.0032432 · 3.23 Impact Factor
Show more