Behavioral and Neurochemical Consequences of Subacute Acetamiprid Administration in a Mice Model

Document Type : Original Article

Authors

Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq

10.21608/javs.2025.413743.1707

Abstract

Acetamiprid, a neonicotinoid insecticide, effectively controls a wide range of crop pests and fleas on livestock and pets. This research examined the neurobehavioral and biochemical consequences of subacute, low-dose oral exposure to acetamiprid in adult mice. The study population was divided into four groups (5 mice/group), including one control group, while the remaining groups received 3.14, 6.29, and 12.59 mg/kg acetamiprid orally three times per week for a duration of 28 days. Behavioral evaluations indicated a clear dose-dependent decline in motor performance, spatial learning, and memory. Reduced rearing activity in the open-field test, poorer outcomes in the negative geotaxis assessment, and fewer head-poking events were indicative of these impairments. Animals treated with higher doses (6.29 and 12.59 mg/kg) also exhibited shorter wire-hanging endurance times and reduced alternation in the T-maze, pointing to deficits in working memory. Biochemical investigations revealed notable reductions in cholinesterase activity in both plasma and brain tissues, coupled with pronounced oxidative stress, as evidenced by increased malondialdehyde levels and decreased glutathione content. Such alterations emerged as early as the 14th day of treatment and persisted until the 28th day. Collectively, the results indicate that subacute acetamiprid exposure can interfere with cholinergic signaling, promote oxidative injury, and compromise both cognitive and motor abilities in mice. Additional studies are needed to clarify the long-term neurodevelopmental risks associated with neonicotinoid exposure in mammals.

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ABDUL HAMEED, Y. M., and NASER, A. S., 2025. Exploring The Anxiolytic and Neurobehavioral Benefits of Serratiopeptidase in Mice. Journal of Applied Veterinary Sciences, 10 (1): 57-63. https://dx.doi.org/10.21608/javs.2024.330246.1455
ALEMDAR, N. T., DEMIR, S., YULUG, E., KULABER, A., DEMIR, E. A., ERDOGAN, N. S., BALKAN, B., and YILMAZ, O., 2025. Acetamiprid-induced testicular toxicity in mice: ameliorative effect and potential mechanisms of morin. BMC Complementary Medicine and Therapies, 25(1): 1–12. https://doi.org/10.1186/s12906-025-04983-y
AL-HAMADANY, N. S., and AL-ZUBAIDY, M. H., 2023. Evaluating the toxic oral doses of iron oxide nanoparticles in mice. Iraqi Journal of Veterinary Sciences, 37(4):801–811 https://doi.org/10.33899/ijvs.2023.138368.2796
AL-HAMADANY, N. A., and ALZUBAIDY, M. H., 2023. Sub-acute Effects of α-Fe2O3 Nanoparticles on Some Biochemical Parameters in Mice. Journal of Applied Veterinary Sciences, 8 (3): 46-53. https://dx.doi.org/10.21608/javs.2023.210749.1232
AL-NAJMAWI, T. K., and AL-ZUBAIDY, M. H., 2022. Acute toxicity events of ivermectin in chicks' model. Iraqi Journal of Veterinary Sciences, 36(4): 1119– 1124. https://doi.org/10.33899/ijvs.2022.133188.2188
AL-SHALCHI, R. F., and MOHAMMAD, F. K., 2024. Alterations of neurobehavioral performance, blood and brain cholinesterase activities and cholesterol levels by repeated statin treatments in mice. Bulletin of Pharmaceutical Sciences Assiut University, 47(1): 415–425.https://doi.org/10.21608/bfsa.2024.270145.2033
AL-ZUBAIDY, M. H. I. 2021. Acute neurotoxicity of acetaminophen in chicks. Veterinarski Arhiv, 91(4): 379–387. https://doi.org/10.24099/vet.arhiv.0950
AL-ZUBAIDY, M. H., I., and AMIN, S. M., 2019. Cholinesterase inhibition in chicks treated with manganese chloride. Iraqi Journal of Veterinary Sciences. 32(2):37-42. https://doi.org/10.33899/ijvs.2019.153875
AL-ZUBAIDY, M. H. I., and MOHAMMAD, F. K., 2007. Metoclopramide protection of diazinon-induced toxicosis in chickens. Journal of Veterinary Science, 8(3): 249–254. https://doi.org/10.4142/jvs.2007.8.3.249
AL-ZUBAIDY, M. H. I., and MOHAMMAD, F., K., 2013. Effects of acute manganese neurotoxicity in young chicks. Arhiv za Higijenu Rada i Toksikologiju, 64(1): 69–75. https://doi.org/10.2478/10004-1254-64-2013-2222
BALLINGER, E., C., ANANTH, M., TALMAGE, D., A., and ROLE, L., W. 2016. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron, 91(6): 1199–1218. https://doi.org/10.1016/j.neuron.2016.09.006
BLOKHINA, O., VIROLAINEN, E., and FAGERSTEDT, K., V., 2003. Antioxidants, oxidative damage and oxygen deprivation stress: a review. Annals of Botany, 91(2): 179–194. https://doi.org/10.1093/aob/mcf118
CAMMAROTA, M., BEVILAQUA, L. R. M., BONINI, J. S., ROSSATTO, J. I., MEDINA, J., H., and IZQUIERDO, N., 2004. Hippocampal glutamate receptors in fear memory consolidation. Neurotoxicity Research, 6: 205–211. https://doi.org/10.1007/bf03033222
DEACON, R. M. J. 2013. Measuring the strength of mice. Journal of Visualized Experiments, (76): e2610. https://doi.org/10.3791/2610
DHOUÏB, I. B., ANNABI, A., DOGHRI, R., REJEB, I., DALLAGI, Y., BDIRI, Y., JAMOUSSI, K., ABID-ESSEFI, S., and BÉJAOUI, S., 2017. Neuroprotective effects of curcumin against acetamiprid-induced neurotoxicity and oxidative stress in the developing male rat cerebellum: biochemical, histological, and behavioral changes. Environmental Science and Pollution Research, 24: 27515–27524. https://doi.org/10.1007/s11356-017-0331-5
EL-BIALY, B. E. S., ABD ELDAIM, M. A., HASSAN, A., and ABDEL-DAIM, M. M., 2020. Ginseng aqueous extract ameliorates lambda-cyhalothrin–acetamiprid insecticide mixture for hepatorenal toxicity in rats: role of oxidative stress-mediated proinflammatory and proapoptotic protein expressions. Environmental Toxicology, 35:(2), 124–135. https://doi.org/10.1002/tox.22848
EL-GENDY, K. S., ALY, N. M., MAHMOUD, F. H., and ALLAH, D. A., 2022. Toxicological assessment of sublethal dose of acetamiprid in male mice and the efficacy of quercetin. Pesticide Biochemistry and Physiology, 184: 105078. https://doi.org/10.1016/j.pestbp.2022.105078
GASMI, S., CHAFAA, S., LAKROUN, Z., ROUABHI, R., TOUAHRIA, C., KEBIECHE, M., CHERIF, H., and BOUKHALF, A. A., 2019. Neuronal apoptosis and imbalance of neurotransmitters induced by acetamiprid in rats. Toxicological and Environmental Health Sciences, 11: 305–311. https://doi.org/10.1007/s13530-019-0417-1
GASMI, S., KEBIECHE, M., ROUABHI, R., TOUAHRIA, C., LAHOUEL, A., LAKROUN, Z., CHERIF, H., and BOUKHALFA, A., 2017. Alteration of membrane integrity and respiratory function of brain mitochondria in the rats chronically exposed to a low dose of acetamiprid. Environmental Science and Pollution Research, 24: 22258–22264. https://doi.org/10.1007/s11356-017-9901-9
KARA, M., YUMRUTAS, O., DEMIR, C. F., OZDEMIR, H. H., BOZGEYIK, I., COSKUN, S., KAZAZ, S. N., KAZAZ, N., and ALTUNAY, S., 2015. Insecticide imidacloprid influences cognitive functions and alters learning performance and related gene expression in a rat model. International Journal of Experimental Pathology, 96(5): 332–337. https://doi.org/10.1111/iep.12139
KARACA, B. U., ARICAN, Y. E., BORAN, T., BINAY, S., OKYAR, A., KAPTAN, E., AYDIN, M. S., KILINC, A., and AKSOY, M., 2019. Toxic effects of subchronic oral acetamiprid exposure in rats. Toxicology and Industrial Health, 35 (11–12): 679–687. https://doi.org/10.1177/0748233719893203
KHALIL, H. A., and FARIS, G. A., 2025. A Study Investigating the Synergistic Analgesic Effects of Nefopam and Medetomidine in a Multimodal Pain Management Approach in Mice. Journal of Applied Veterinary Sciences, 10 (3): 129 136. https://doi.org/10.21608/javs.2025.389940.1628
KHOVARNAGH, N., and SEYEDALIPOUR, B., 2021. Antioxidant, histopathological and biochemical outcomes of short-term exposure to acetamiprid in liver and brain of rat: The protective role of N-acetylcysteine and S-methylcysteine. Saudi Pharmaceutical Journal, 29(3): 280–289. https://doi.org/10.1016/j.jsps.2021.02.004
KUTLU, M., G., and GOULD, T., J. 2015. Nicotinic receptors, memory, and hippocampus. In Neurobiology of Nicotine and Tobacco, 137–163. https://doi.org/10.1007/978-3-319-13665-3_6
MITSUSHIMA, D., SANO, A., and TAKAHASHI, T., 2013. A cholinergic trigger drives learning-induced plasticity at hippocampal synapses. Nature Communications, 4(1): 2760. https://doi.org/10.1038/ncomms3760
OLAJIDE, O. J., GBADAMOSI, I. T., YAWSON, E. O., AROGUNDADE, T., LEWU, F. S., OGUNRINOLA, K. Y., ABUBAKAR, O. L., and SULEIMAN, M., 2021. Hippocampal degeneration and behavioral impairment during Alzheimer-like pathogenesis involves glutamate excitotoxicity. Journal of Molecular Neuroscience, 71: 1205–1220. https://doi.org/10.1007/s12031-020-01747-w
ONAOLAPO, O. J., ONAOLAPO, A. Y., MOSAKU, T. J., AKANJI, O. O., and ABIODUN, O., R., 2012. Elevated plus maze and Y-maze behavioral effects of subchronic, oral low dose monosodium glutamate in Swiss albino mice. Journal of Pharmacy and Biological Sciences, 3(4): 21–27. http://dx.doi.org/10.9790/3008-0342127
PETRIE, A., and WATSON, P., 2013. Statistics for veterinary and animal science. 3rd ed. John Wiley & Sons.
PHOGAT, A., SINGH, J., KUMAR, V., and MALIK, V., 2022. Toxicity of the acetamiprid insecticide for mammals: a review. Environmental Chemistry Letters, 1–26. https://doi.org/10.1007/s10311-021-01353-1
POTHU, U. K., THAMMISETTY, A. K., and NELAKUDITI, L. K., 2019. Evaluation of cholinesterase and lipid profile levels in chronic pesticide exposed persons. Journal of Family Medicine and Primary Care, 8(6): 2073–2078.  https://doi.org/10.4103/jfmpc.jfmpc_440_19
PREISER, J. 2012. Oxidative stress. Journal of Parenteral and Enteral Nutrition, 36(2): 147–154. https://doi.org/10.1177/0148607111434963
SAITO, H., FURUKAWA, Y., SASAKI, T., KITAJIMA, S., KANNO, J., and TANEMURA, K., 2023. Behavioral effects of adult male mice induced by low-level acetamiprid, imidacloprid, and nicotine exposure in early life. Frontiers in Neuroscience, 17:1239808. https://doi.org/10.3389/fnins.2023.1239808
SANO, K., ISOBE, T., YANG, J., WIN-SHWE, T. T., YOSHIKANE, M. NAKAYAMA, S., F., NAKAJIMA, D., KASHIWA, H., and SHINKAI, Y., 2016. In utero and lactational exposure to acetamiprid induces abnormalities in socio-sexual and anxiety-related behaviors of male mice. Frontiers in Neuroscience, 10: 228. https://doi.org/10.3389/fnins.2016.00228
SHAMSI, M., SOODI, M., SHAHBAZI, S., and OMIDI, A., 2021. Effect of acetamiprid on spatial memory and hippocampal glutamatergic system. Environmental Science and Pollution Research, 28: 27933–27941.https://doi.org/10.1007/s11356-020-12314-6
SINGH, T. B., MUKHOPADHAYAY, S. K., SAR, T. K., and GANGULY, S., 2012. Acetamiprid induces toxicity in mice under experimental conditions with prominent effect on the hematobiochemical parameters. Journal of Drug Metabolism and Toxicology, 3(6): 134. http://dx.doi.org/10.4172/2157-7609.1000134
SZYNDLER, J., PIECHAL, A., BLECHARZ-KLIN, K., SKÓRZEWSKA, A., MACIEJAK, P., WALKOWIAK, J., TURZYŃSKA, D., LEWANDOWSKA, A., and WISŁOWSKA, A., 2006. Effect of kindled seizures on rat behavior in water Morris maze test and amino acid concentrations in brain structures. Pharmacological Reports, 58(1): 75–82.PMID: 16531633
TERAYAMA, H., ENDO, H., TSUKAMOTO, H., MATSUMOTO, K., UMEZU, M., KANAZAWA, T., MITSUHASHI, T., SHIMIZU, T., KAKUTANI, H., and TANAKA, M., 2016. Acetamiprid accumulates in different amounts in murine brain regions. International Journal of Environmental Research and Public Health, 13(10): 937.https://doi.org/10.3390/ijerph13100937
TOMIZAWA, M., and CASIDA, J. E., 2005. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annual Review of Pharmacology and Toxicology, 45(1): 247–268. https://doi.org/10.1146/annurev.pharmtox.45.120403.095930