Developmental Effects of Malathion Exposure on Recognition Memory and Spatial Learning in Males Wistar Rats

DOI: 10.4236/jbbs.2013.33033   PDF   HTML   XML   3,611 Downloads   5,577 Views   Citations


Most cognitive effects of Organophosphate Pesticides (OP) are induced after exposure to parathion, chlorpyrifos and diazinon, which the usage has been restricted because of overt signs of their toxicities. In this study, we investigate whether developmental exposure to Malathion could impair spatial learning and recognition memory in male rats. Animals exposed by intragastric route, from in utero to young adult stage, to incremental doses of Malathion dissolved in corn oil; 100, 200 and 300 mg/kg of body weight, and one control group are given corn oil. Then, cognitive and behaveioral abilities are assessed using Barnes maze and object recognition memory task. Malathion administration at 300 mg/kg is toxic to pregnant dams, and pups are stillborns. Rats exposed to 200 mg/kg make a significant working memory error, and require more time to find an escape box during the initial training phase of Barnes maze. However, fewer errors are made in rats exposed to 100 mg/kg. For reversal learning task, the high dose group shows great deficits in spatial strategy to locate the new position of the box. With respect to recognition task, both dose 100 and 200 mg/kg impair significant short-term (2 h after habituation phase) object recognition memory, but long-term (24 h after habituation phase) recognition memory is intact in high dose group. The current study also reveals that all treatments induce high significant neocortex acetylcholinesterase (AChE) activity inhibition, but 100 mg/kg dose is not sufficient to disrupt great hippocampal activity alteration. These results suggest that developmental exposure to Malathion, despite low toxicity described, may induce late-emerging spatial learning and recognition memorialterations. Moreover, Cortical and hippocampal area that support strongly these behaviors remain sensitive to incremental doses of Malathion.

Share and Cite:

P. N’Go, F. Azzaoui, P. Soro, M. Samih, A. Ahami, M. Najimi and F. Chigr, "Developmental Effects of Malathion Exposure on Recognition Memory and Spatial Learning in Males Wistar Rats," Journal of Behavioral and Brain Science, Vol. 3 No. 3, 2013, pp. 331-340. doi: 10.4236/jbbs.2013.33033.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] B. Eskenazi, A. R. Marks, A. Bradman, K. Harley, D. B. Barr, C. Johnson, et al., “Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children,” Environmental Health Perspectives, Vol. 115, No. 5, 2007, pp. 792-798.
[2] C. Lu, K. Toepel, R. Irish, R. A. Fenske, D. B. Barr and R. Bravo, “Organic Diets Significantly Lower Children’s Dietary Exposure to Organophosphorus Pesticides,” Environmental Health Perspectives, Vol. 114, No. 2, 2006, pp. 260-263.
[3] M. K. Morgan, L. S. Sheldon, C. W. Croghan, P. A. Jones, G. L. Robertson, J. C. Chuang, N. K. Wilson and C. W. Lyu, “Exposures of Preschool Children to Chlorpyrifos and Its Degradation Product 3,5,6-trichloro-2-pyridinol in Their Everyday Environments,” Journal of Exposure Analysis and Environmental Epidemiology, Vol. 15, No. 4, 2005, pp. 297-309.
[4] M. Maroni, C. Colosio, A. Ferioli and A. Fait, “Biological Monitoring of Pesticide Exposure: A Review. Introduction,” Toxicology, Vol. 143, No. 1, 2000, pp. 1-118.
[5] D. J. Ecobichon, “Pesticides and Neurological Diseases,” CRC Press, Boca Raton, 1994, p. 381.
[6] L. M. Wang, W. H. Ye, S. S. Zhou, K. D. Lin, M. R. Zhao and W. P. Liu, “Acute and Chronic Toxicity of Organophosphate Monocrotophos to Daphnia Magna,” Journal of Environmental Science and Health, Part B, Vol. 44, No. 1, 2009, pp. 38-43.
[7] T. C. Kwong, “Organophosphate Pesticides: Biochemistry and Clinical Toxicology,” Therapeutic Drug Monitoring, Vol. 24, No. 1, 2002, pp. 144-149. doi:10.1097/00007691-200202000-00022
[8] K. P. Cantor, A. Blair, G. Everett, et al., “Pesticides and Other Agricultural Risk Factors for Non-Hodgkin’s Lymphoma among Men in Iowa and Minnesota,” Cancer Research, Vol. 52, No. 9, 1992, pp. 2447-2455.
[9] S. H. Zahm, D. D. Weisenburger, R. C. Saal, et al., “The Role of Agricultural Pesticide Use in the Development of Non-Hodgkin’s Lymphoma in Women,” Archives of Environmental Health, Vol. 48, No. 5, 1993, pp. 353-358. doi:10.1080/00039896.1993.9936725
[10] H. H. McDuffie, P. Pahwa, J. R. McLaughlin, et al., “Non-Hodgkin’s Lymphoma and Specific Pesticide Exposures in Men: Cross-Canada Study of Pesticides and Health,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 10, No. 11, 2001, pp. 1155-1163.
[11] L. Brenner, “Malathion,” Journal of Pesticide Reform, Vol. 12, 1992, p. 29
[12] E. Bustos-Obregón and P. Gonzáles-Hormazabal, “Effect of a Single Dose of Malathion on Spermatogenesis in Mice,” Asian Journal of Andrology, Vol. 5, No. 2, 2003, pp. 105-107.
[13] M. Abdollahi, M. Donyavi, S. Pournourmohammadi and M. Saadat, “Hyperglycemia Associated with Increased Hepatic Glycogen Phosphorylase and Phosphoenolpyruvate Carboxykinase Activities in Rats Following Subchronic Exposure to Malathion,” Comparative Biochemistry and Physiology Part C: Pharmacology, Toxicology and Endocrinology, Vol. 137, No. 4, 2004, pp. 343-347.
[14] T. A. Slotkin, “Developmental Cholinotoxicants: Nicotine and Chlorpyrifos,” Environmental Health Perspectives, Vol. 107, Suppl. 1, 1999, pp. 71-80.
[15] P. Z. Ruckart, K. Kakolewski, F. J. Bove and W. E. Kaye, “Long-Term Neurobehavioral Health Effects of Methyl Nparathion Exposure in Children in Mississippi and Ohio,” Environmental Health Perspectives, Vol. 112, No. 1, 2004, pp. 46-51. doi:10.1289/ehp.6430
[16] Sanborn, Margaret, et al., “Systematic Review of Pesticide Human Health Effects,” Ontario College of Family Physicians Toronto, Toronto, 23 April 2004.
[17] F. L. Assini, K. D. Zanette, P. S. Brocardo, P. Pandolfo, A. L. Rodrigues and R. N. Takahashi, “Behavioral Effects and ChE Measures after Acute and Repeated Administration of Malathion in Rats,” Environmental Health Perspectives, Vol. 20, No. 3, 2005, pp. 443-449. doi:10.1016/j.etap.2005.05.007
[18] C. I. Acker, A. C. Souza, S. Pinton, J. T. Da Rocha, C. A. Friggi, R. Zanella and C. W. Nogueira, “Repeated Malathion Exposure Induces Behavioral Impairment and AChE Activity Inhibition in Brains of Rat Pups,” Ecotoxicology and Environmental Safety, Vol. 74, No. 8, 2011, pp. 2310-2315. doi:10.1016/j.ecoenv.2011.07.035
[19] T. A. Slotkin, T. L. Lassiter, I. T. Ryde, N. Wrench, E. D. Levin and F. J. Seidler, “Consumption of a High-Fat Diet in Adulthood Ameliorates the Effects of Neonatal Parathion Exposure on Acetylcholine Systems in Rat Brain Regions,” Environmental Health Perspectives, Vol. 117, No. 6, 2009, pp. 916-922.
[20] S. X. Guo-Ross, , J. E. Chambers, , E. C. Meek and R. L. Carr, “Altered Muscarinic Acetylcholine Receptor Subtype Binding in Neonatal Rat Brain Following Exposure to Chlorpyrifos or Methyl Parathion,” Toxicological Sciences, Vol. 100, No. 1, 2007, pp. 118-127. doi:10.1093/toxsci/kfm195
[21] J. Tang, R. L. Carr and J. E. Chambers, “The Effects of Repeated Oral Exposures to Methyl Parathion on Rat Brain Cholinesterase and Muscarinic Receptors during Postnatal Development,” Toxicological Sciences, Vol. 76, No. 2, 2003, pp. 400-406. doi:10.1093/toxsci/kfg245
[22] F. O.Johnson, J. E. Chambers, C. A. Nail, S. Givaruangsawat and R. L. Carr, “Developmental Chlorpyrifos and Methyl Parathion Exposure Alters Radial Arm Maze Performance in Juvenile and Adult Rats,” Toxicological Sciences, Vol. 109, No. 1, 2009, pp. 132-142. doi:10.1093/toxsci/kfp053
[23] L. M. Icenogle, N. C. Christopher, W. P. Blackwelder, D. P. Caldwell, D. Qiao, F. J. Seidler, T. A. Slotkin and E. D. Levin, “Behavioral Alterations in Adolescent and Adult Rats Caused by a Brief Subtoxic Exposure to Chlorpyrifos during Neurulation,” Neurotoxicology and Teratology, Vol. 26, No. 1, 2004, pp. 95-101. doi:10.1016/
[24] A. Ennaceur, “One-Trial Object Recognition in Rats and Mice: Methodological and Theoretical Issues,” Behavioural Brain Research, Vol. 215, No. 2, 2010, pp. 244254.
[25] A. Ennaceur and J. Delacour, “A New One-Trial Test for Neurobiological Studies of Memory in Rats. 1: Behavioral Data,” Behavioural Brain Research, Vol. 31, No. 1, 1988, pp. 47-59 doi:10.1016/0166-4328(88)90157-X
[26] C. A. Barnes, “Memory Deficits Associated with Senescence: A Neurophysiological and Behavioral Study in the Rat,” Journal of Comparative & Physiological Psychology, Vol. 93, No. 1, 1979, pp. 74-104.
[27] I. Fedorova, N. Hussein, M.H. Baumann, C. Di Martino and N. Salem, Jr. “An n-3 Fatty Acid Deficiency Impairs Rat Spatial Learning in the Barnes Maze,” Behav Neurosci. Vol. 123, No. 1, 2009, pp. 196-205. doi:10.1037/a0013801
[28] U. Greferath, A. Bennie, A. Kourakis and G. L. Barrett, “Impaired Spatial Learning in Aged Rats Is Associated with Loss of p75-Positive Neurons in the Basal Forebrain,” Neuroscience, Vol. 100, No. 2, 2000, pp. 363-373. doi:10.1016/S0306-4522(00)00260-8
[29] J. M. Daniel, A. J. Fader, A. L. Spencer and G. P. Dohanich, “Estrogen Enhances Performance of Female Rats during Acquisition of a Radial Arm Maze,” Hormones and Behavior, Vol. 32, No. 3, 1997, pp. 217-225.
[30] D. S. Olton, “The Radial Arm Maze as a Tool in Behavioral Pharmacology,” Physiology & Behavior, Vol. 40, No. 6, 1987, pp. 793-797. doi:10.1016/0031-9384(87)90286-1
[31] G. L. Ellman, K. D. Courtney, V. R. M. Andres and R. M. Featherstone, “A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity,” Biochemical Pharmacology, Vol. 7, No. 2, 1961, pp. 88-95. doi:10.1016/0006-2952(61)90145-9
[32] F.-Z. Azzaoui, H. Hami, M. El-Hioui, S. Boulbaroud and A. Ahami “Attempt at the Determination of Aluminum Nitrate LD50 and the Study of Its Neurotoxicological Effect in Wistar Rat,” Biology and Medicine, Vol. 4, No. 2, 2012, pp. 89-94.
[33] H. R. Santos, W. M. Cintra, Y. Aracava, C. M. Maciel, N. G. Castro, E. X. Albuquerque, “Spine Density and Dendritic Branching Pattern of Hippocampal CA1 Pyramidal Neurons in Neonatal Rats Chronically Exposed to the Organophosphate Paraoxon,” Neurotoxicology, Vol. 25, No. 3, 2004, pp. 481-494.
[34] A. L. Jones and L. Karalliedde, “Poisoning,” In: N. A. Boon, N. R. Colledge, S. S. Davidson and B. R. Walker, Eds., Davidson’s Principles and Practice of Medicine, 20th Edition, Churchill Livingstone, Edinburgh, 2006, pp. 203-226.
[35] M. Antunes and G. Biala. “The Novel Objects Recognition Memory: Neurobiology, Test Procedure, and Its Modifications,” Cognitive Processing, Vol. 13, No. 2, 2012, pp. 93-110. doi:10.1007/s10339-011-0430-z
[36] M. L. Reger, D. A. Hovda and C. C. Giza, “Ontogeny of Rat Recognition Memory Measured by the Novel Object Recognition Task,” Developmental Psychobiology, Vol. 51, No. 8, 2009, pp. 672-678. doi:10.1002/dev.20402
[37] T. T. Win-Shwe, D. Nakajima, S. Ahmed and H. Fujimaki, “Impairment of Novel Object Recognition in Adulthood after Neonatal Exposure to Diazinon,” Archives of Toxicology, Vol. 87, No. 4, 2012, pp. 753-762.
[38] R. S. Hammond, L. E. Tull and R. W. Stackman, “On the Delay-Dependent Involvement of the Hippocampus in Object Recognition Memory,” Neurobiology of Learning and Memory, Vol. 82, No. 1, 2004, pp. 26-34. doi:10.1016/j.nlm.2004.03.005
[39] J. R. Clarke, M. Cammarota, A. Gruart, I. Izquierdo and J. M. Delgado-Garcia, “Plastic Modifications Induced by Object Recognition,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 6, 2010, pp. 2652-2657. doi:10.1073/pnas.0915059107
[40] B. D. Winters and T. J. Bussey, “Removal of Cholinergic Input to Perirhinal Cortex Disrupts Object Recognition but Not Spatial Working Memory in the Rat,” European Journal of Neuroscience, Vol. 21, No. 8, 2005, pp. 22632270. doi:10.1111/j.1460-9568.2005.04055.x
[41] C. F. Hohmann, “A Morphogenetic Role for Acetylcholine in Mouse Cerebral Neocortex,” Neuroscience & Biobehavioral Reviews, Vol. 27, No. 4, 2003, pp. 351-363. doi:10.1016/S0149-7634(03)00066-6
[42] J. Yanai, “Neurobehavioral Teratology,” Elsevier, Amsterdam, 1984.
[43] T. A. Slotkin, “Cholinergic Systems in Brain Development and Disruption by Neurotoxicants: Nicotine, Environmental Tobacco Smoke, Organophosphates,” Toxicology and Applied Pharmacology, Vol. 198, No. 2, 2004, pp. 132-151. doi:10.1016/j.taap.2003.06.001
[44] B. Eskenazi, A. Bradman and R. Castorina, “Exposures of Children to Organophosphate Pesticides and Their Potential Adverse Health Effects,” Environmental Health Perspectives, Vol. 107, Suppl. 3, 1999, pp. 409-419. doi:10.1289/ehp.99107s3409
[45] G. Sarkisyan and P. B. Hedlund, “The 5-HT7 Receptor Is Involved in Allocentric Spatial Memory Information Processing,” Behavioural Brain Research, Vol. 202, No. 1, 2009, pp. 26-31. doi:10.1016/j.bbr.2009.03.011
[46] T. A. Slotkin and F. J. Seidler, “Developmental Exposure to Terbutaline and Chlorpyrifos, Separately or Sequentially, Elicits Presynaptic Serotonergic Hyperactivity in Juvenile and Adolescent Rats,” Brain Research Bulletin, Vol. 73, No. 4-6, 2007, pp. 301-309. doi:10.1016/j.brainresbull.2007.04.004
[47] J. E. Aldridge, E. D. Levin, F. J. Seidler and T. A. Slotkin, “Developmental Exposure of Rats to Chlorpyrifos Leads to Behavioral Alterations in Adulthood, involving Serotonergic Mechanisms and Resembling Animal Models of Depression,” Environmental Health Perspectives, Vol. 113, No. 5, 2005, pp. 527-531.
[48] G. Koopmans, A. Blokland, P. van Nieuwenhuijzen and J. Prickaerts, “Assessment of Spatial Learning Abilities of Mice in a New Circular Maze,” Physiology & Behavior, Vol. 79, No. 4-5, 2003, pp. 683-693. doi:10.1016/S0031-9384(03)00171-9
[49] T. Nakashiba, D. L. Buhl, T. J. McHugh and S. Tonegawa, “Hippocampal CA3 Output is Crucial for Ripple-Associated Reactivation and Consolidation of Memory,” Neuron, Vol. 62, No. 6, 2009, pp. 781-787.
[50] H. Eichenbaum, “Cortico-Hippocampal System for Declarative Memory,” Nature Reviews Neuroscience, Vol. 1, No. 1, 2000, pp. 41-50.
[51] S. Brimijoin and C. Koenigsberger, “Cholinesterases in Neural Development: New Findings and Toxicologic Implications,” Environmental Health Perspectives, Vol. 107, Suppl. 1, 1999, pp. 59-64.
[52] J. W. Bigbee, K. V. Sharma, J. J. Gupta and J. L. Dupree, “Morphogenic Role for Acetylcholinesterase in Axonal Outgrowth during Neural Development,” Environmental Health Perspectives, Vol. 107, Suppl. 1, 1999, pp. 81-87.
[53] M. Grifman, N. Galyam, S. Seidman and H. Soreq, “Functional Redundancy of Acetylcholinesterase and Neuroligin in Mammalian Neuritogenesis,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 23, 1998, pp. 13935-13940. doi:10.1073/pnas.95.23.13935
[54] D. Qiao, F. J. Seidler, Y. Abreu-Villaca, C. A. Tate, M. M. Cousins and T. A. Slotkin, “Chlorpyrifos Exposure during Neurulation: Cholinergic Synaptic Dysfunction and Cellular Alterations in Brain Regions at Adolescence and Adulthood,” Brain Research. Developmental Brain Research, Vol. 148, No. 1, 2004, pp. 43-52.
[55] A. D. Campana, F. Sanchez, C. Gamboa, M, J. de Gómez-Villalobos, F. De La Cruz, S. Zamudio and G. Flores, “Dendritic Morphology on Neurons from Prefrontal Cortex, Hippocampus, and Nucleus Accumbens Is Altered in Adult Male Mice Exposed to Repeated Low Dose of Malathion,” Synapse, Vol. 64, No. 4, 2008, pp. 283-290. doi:10.1002/syn.20494
[56] G. Sarkisyan and P. B. Hedlund, “The 5-HT7 Receptor Is Involved in Allocentric Spatial Memory Information Processing,” Behavioural Brain Research, Vol. 202, No. 1, 2009, pp. 26-31. doi:10.1016/j.bbr.2009.03.011
[57] E. D. Levin, N. Addy, A. Nakajima, N. C. Christopher, F. J. Seidler and T. A. Slotkin, “Persistent Behavioral Consequences of Neonatal Chlorpyrifos Exposure in Rats,” Developmental Brain Research, Vol. 130, No. 1, 2001, pp. 83-89. doi:10.1016/S0165-3806(01)00215-2
[58] R. P. Kesner, “Subregional Analysis of Mnemonic Functions of the Prefrontal Cortex in the Rat,” Psychobiology, Vol. 28, No. 2, 2000, pp. 219-228.
[59] A. Louilot, K. Taghzouti, H. Simon and M. Le Moal, “Limbic System, Basal Ganglia, and Dopaminergic Neurons. Executive and Regulatory Neurons and Their Role in the Organization of Behavior,” Brain, Behavior and Evolution, Vol. 33, No. 2-3, 1989, pp. 157-161. doi:10.1159/000115920
[60] E. J. Nestler and W. A. Carlezon Jr., “The Mesolimbic Dopamine Reward Circuit in Depression,” Biological Psychiatry, Vol. 59, No. 12, 2006, pp. 1151-1159. doi:10.1016/j.biopsych.2005.09.018
[61] S. B. Floresco, S. Ghods-Sharifi, C. Vexelman and O. Magyar, “Dissociable Roles for the Nucleus Accumbens Core and Shell in Regulating Set Shifting,” The Journal of Neuroscience, Vol. 26, No. 9, 2006, pp. 2449-2457. doi:10.1523/JNEUROSCI.4431-05.2006
[62] T. A. Slotkin, B. E. Bodwell, E. D. Levin and F. J. Seidler, “Neonatal Exposure to Low Doses of Diazinon: Long-Term Effects on Neural Cell Development and Acetylcholine Systems,” Environmental Health Perspectives, Vol. 116, No. 3, 2008, pp. 340-348. doi:10.1289/ehp.11005
[63] S. Ghods-Sharifi, D. M. Haluk and S. B. Floresco, “Differential Effects of Inactivation of the Orbitofrontal Cortex on Strategy Set-Shifting and Reversal Learning,” Neurobiology of Learning and Memory, Vol. 89, No. 4, 2008, pp. 567-573. doi:10.1016/j.nlm.2007.10.007
[64] R. N. Cardinal, J. A. Parkinson, J. Hall and B. J. Everitt, “Emotion and Motivation: The Role of the Amygdala, Ventral Striatum, and Prefrontal Cortex,” Neuroscience & Biobehavioral Reviews, Vol. 26, No. 3, 2002, pp. 321-352. doi:10.1016/S0149-7634(02)00007-6
[65] I. Toni and R. E. Passingham, “Prefrontal-Basal Ganglia Pathways Are Involved in the Learning of Arbitrary Visuomotor Associations: A PET Study,” Experimental Brain Research, Vol. 127, No. 1, 1999, pp. 19-32. doi:10.1007/s002210050770
[66] M. G. Purisai, A. L. McCormack, S. Cumine, J. Li, M. Z. Isla and D. A. Di Monte, “Microglial Activation as a Priming Event Leading to Paraquat-Induced Dopaminergic Cell Degeneration,” Neurobiology of Disease, Vol. 25, No. 2, 2007, pp. 392-400. doi:10.1016/j.nbd.2006.10.008

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.