Oral Amodiaquine, Artesunate and Artesunate Amodiaquine Combination Affects Open Field Behaviors and Spatial Memory in Healthy Swiss Mice


Effects of amodiaquine, artesunate and artesunate amodiaquine combination on open field novelty-induced behaviors and spatial memory in healthy mice were studied. Forty mice were used in the open field and fifty each in the radial arm maze and Y maze; mice were assigned into four or five groups of ten each, Group A served as control (distilled water), Groups B, C and D received artesunate (4 mg/kg), amodiaquine (10 mg/kg) and artesunate-amodiaquine combination (4 mg/kg and10 mg/kg) respectively, while Group E animals (for the cognition tests) were given scopolamine (2 mg/kg). Drugs and vehicle were administered orally for three days. Results were analysed by one way analysis of variance followed by a posthoc test. Results showed that artesunate and amodiaquine either in combination or administered singly caused a significant increase in open field novelty-induced horizontal locomotion and rearing. Grooming in the open field showed increments in the artesunate alone and artesunate amodiaquine groups while significant reductions in spatial memory were also seen in the cognition models used.

Share and Cite:

A. Onaolapo, O. Onaolapo, E. Awe, S. Oloyede and A. Joel, "Oral Amodiaquine, Artesunate and Artesunate Amodiaquine Combination Affects Open Field Behaviors and Spatial Memory in Healthy Swiss Mice," Journal of Behavioral and Brain Science, Vol. 3 No. 8, 2013, pp. 569-575. doi: 10.4236/jbbs.2013.38059.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] T. Gordi and E. I. Lepist, “Artemisinin Derivatives: Toxic for Laboratory Animals, Safe for Humans?” Toxicology Letters, Vol. 147, No. 2, 2004, pp. 99-107.
[2] World Health Organization, “Antimalarial Drug Combination Therapy,” Report of a WHO Technical Consultation, Geneva, 2001.
[3] M. Adjuik, P. Agnamey, A. Babiker, S. Borrmann, P. Brasseur, M. Cisse, F. Cobelens, S. Diallo, J. F. Faucher, P. Garner, S. Gikunda, P. G. Kremsner, S. Krishna, B. Lell, M. Loolpapit, P. B. Matsiegui, M. A. Missinou, J. Mwanza, F. Ntoumi, P. Olliaro, P. Osimbo, P. Rezbach, E. Some and W. R. Taylor, “Amodiaquine-Artesunate versus Amodiaquine for Uncomplicated Plasmodium falciparum Malaria in African Children: A Randomised, Multicentre Trial,” The Lancet, Vol. 359, No. 9315, 2002, pp, 1365-1372.
[4] F. Abacassamo, S. Enosse, J. J. Aponte, F. X. Gomez-Olive, L. Quinto, S. Mabunda, A. Barreto, P. Magnussen, A. M. Ronn, R. Thompson and P. L. Alonso, “Efficacy of Chloroquine, Amodiaquine, Sulphadoxine-Pyrimethamine and Combination Therapy with Artesunate in Mozambican Children with Non-Complicated Malaria,” Tropical Medicine & International Health, Vol. 9, No. 2, 2004, pp. 200-208.
[5] T. K. Mutabingwa, D. Anthony, A. Heller, R. Hallet, J. Ahmed, C. Drakeley, B. M. Greenwood and C. J. Whitty, “Amodiaquine Alone, Amodiaquine+Sulfadoxine-Pyrimethamine, Amodiaquine+Artesunate, and ArtemetherLumefantrine for Outpatient Treatment of Malaria in Tanzanian Children: A Four-Arm Randomized Effectiveness Trial,” The Lancet, Vol. 365, No. 9469, 2005, pp. 1474-1480. http://dx.doi.org/10.1016/S0140-6736(05)66417-3
[6] M. Martin, A. Alaribe, R. Ejemot, A. Oyo-Ita, J. Ekenjoku, C. Nwachukwu, D. Ordu and E. Ezedinachi, “Artemether-Lumefantrine versus Artesunate plus Amodiaquine for Treating Uncomplicated Childhood Malaria in Nigeria: Randomized Controlled Trial,” Malaria Journal, Vol. 5, No. 43, 2006.
[7] T. T. Hien and N. J. White, “Qinghaosu,” The Lancet, Vol. 341, No. 8845, 1993, pp. 603-608.
[8] R. Hutagalung, H. Htoo, P. Nwee, J. Arunkamomkiri, J. Zwang and V. I. Carrara, “A Case-Control Auditory Evaluation of Patients Treated with Artemether-Lumefantrine,” The American Journal of Tropical Medicine and Hygiene, Vol. 74, No. 2, 2006, pp. 211-214.
[9] P. E. Thuma, G. J. Bhat, G. F. Mabeza, C. Osborne, G. Biemba and G. M. Shakankale, “A Randomized Controlled Trial of Arte Motil (Beta-Arteether) in Zambian Children with Cerebral Malaria,” The American Journal of Tropical Medicine and Hygiene, Vol. 62, No. 4, 2000, pp. 524-529.
[10] T. H. Tran, N. P. Day, H. P. Nguyen, T. H. Nguyen, T. H. Tran and P. L. Pham, “A Controlled Trial of Artemether or Quinine in Vietnamese Adults with Severe Falciparum Malaria,” The New England Journal of Medicine, Vol. 335, No. 2,1996, pp. 76-78.
[11] S. Toovey and A. Jamieson, “Response to: Artemisinin Derivatives: Toxic for Laboratory Animals, Safe for Humans?” Toxicology Letters, Vol. 151, No. 3, 2004, pp. 491-492.
[12] L. A. Panossian, N. I. Garga and D. Pelletier, “Toxic Brainstem Encephalopathy after Artemisinins Treatment for Breast Cancer,” Annals of Neurology, Vol. 58, No. 5, 2005, pp. 812-813. http://dx.doi.org/10.1002/ana.20620
[13] R. L. Clark, T. E. K. White, S. A. Clode, I. Gaunt, P. Winstanley and S. A. Ward, “Developmental Toxicity of Artesunate and an Artesunate Combination in the Rat and Rabbit,” Birth Defects Research Part B, Developmental and Reproductive Toxicology, Vol. 71, No. 6, 2004, pp. 380-394. http://dx.doi.org/10.1002/bdrb.20027
[14] G. Schmuck, A.-M. Klaus, F. Krotlinge and F. W. Langewische, “Developmental and Reproductive Toxicity Studies on Artemisone,” Birth Defects Research Part B, Developmental and Reproductive Toxicology,Vol. 86, No. 2, 2009, pp. 131-143.
[15] R. F. Genovese, H. A. Nguyen and S. R. Mog, “Effects of Arteether on an Auditory Radial-Arm Maze Task in Rats,” Physiology & Behavior, Vol. 73, No. 1-2, 2001, pp. 87-91. http://dx.doi.org/10.1016/S0031-9384(01)00462-0
[16] Q. G. Li, S. R. Mog, Y. Z. Si, D. E. Kyle, M. Gettayacamin and W. K. Milhous, “Neurotoxicity and Efficacy of Arteether Related to Its Exposure Times and Exposure Levels in Rodents,” The American Journal of Tropical Medicine and Hygiene, Vol. 66, No. 5, 2002, pp. 516-525.
[17] Y. Si, Q. Li, L. Xie, K. Bennett, P. J. Weina and S. Mog, “Neurotoxicity and Toxicokinetics of Artelinic Acid Following Repeated Oral Administration in Rats,” International Journal of Toxicology, Vol. 26, No. 5, 2007, pp. 401-410. http://dx.doi.org/10.1080/10915810701582913
[18] C. R. Bepler, H. N. Baier, S. McCracken, C. L. Rentschler, F. B. Rogers and J. Lansbury, “A 15 Month Controlled Study of the Effects of Amodiaquine (Camoquin) in Rheumatoid Arthritis,” Arthritis & Rheumatism, Vol. 2, No. 5, 1959, pp. 403-413.
[19] H. Pomeroy, C. Warren, D. Mills and G. M, Clark, “The Effect of Amodiaquine (Camoquin) on the Course of Rheumatoid Arthritis,” Arthritis & Rheumatism, Vol. 2, No. 5, 1959, pp. 396-402.
[20] K. A. Neftel, W. Woodtly, M. Schmid, P. G. Frick and J. Fehr, “Amodiaquine Induced Agranulocytosis and Liver Disease,” British Medical Journal, Vol. 292, 1986, pp. 721-723.
[21] L. N. Markham, E. Giostra, A. Hadengue, M. Rossier, M. Rebsamen and J. Desmeules, “Emergency Liver Transplantation in Amodiaquine-Induced Fulminant Hepatitis,” The American Journal of Tropical Medicine and Hygiene, Vol. 77, No. 1, 2007, pp. 14-15.
[22] O. J. Onaolapo and A. Y. Onaolapo, “Subchronic Oral Bromocriptine Methanesulfonate Enhances Open Field Novelty-Induced Behavior and Spatial Memory in Male Swiss Albino Mice,” Neuroscience Journal, Vol. 2013, 2013, Article ID: 948241.
[23] S. Yoshida, H. Nagumo, T. Yokomine, H. Araki, A. Suzuki and H. Matsuoka, “Plasmodium Berghei Circumvents Immune Responses Induced by Merozoite Surface Protein 1and Apical Membrane Antigen 1-Based Vaccines,” PLoS One, Vol. 5, No. 10, 2010, pp. 1-10.
[24] R. W. Snow, C. A. Guerra, A. M. Noor, H. Y. Myint and S. I. Hay, “The Global Distribution of Clinical Episodes of Plasmodium falciparum Malaria,” Nature, Vol. 434, No. 7030, 2005, pp. 214-217.
[25] W. E. Crusio “Genetic Dissection of Mouse Exploratory Behavior,” Behavioural Brain Research, Vol. 125, No. 1-2, 2001, pp. 127-132.
[26] A. A. Ajayi and O. E. Ukponmwan, “Evidence of Angiotensin II and Endogenous Opioid Modulation of NIR in the Rat,” African Journal of Medicine & Medical Sciences, Vol. 23, No. 3, 1994, pp. 287-290.
[27] I. M. H. Al-Khatib, I. Doè Kmeci and M. Fujiwara, “Differential Role of Nucleus Accumbens and Caudate-Putamen in Mediating the Effect of Nomifensine and Methamphetamine Onambulation and Rearing of Rats in the Open-Field Test,” The Japanese Journal of Pharmacology, Vol. 67, No. 1, 1995, pp. 69-77.
[28] B. D. Sachs, “The Development of Grooming and Its Expression in Adult Animals,” Annals of the New York Academy of Sciences, Vol. 525, 1988, pp. 1-17.
[29] R. L. Terry, “Primate Grooming as a Tension Reduction Mechanism,” The Journal of Psychology: Interdisciplinary and Applied, Vol. 76, No. 1, 1970, pp. 129-136.
[30] B. M. Spruijt, J. A. van Hooff and W. H. Gispen, “Ethology and Neurobiology of Grooming Behavior,” Physiological Reviews, Vol. 72, No. 2, 1992, pp. 825-852.
[31] H. M. Barros, S. L. Tannhauser, M. A. Tannhauser and M. Tannhauser, “The Effects of GABAergic Drugs on Grooming Behaviour in the Open Field,” Pharmacology & Toxicology, Vol. 74, No. 4-5, 1994, pp. 339-344.
[32] A. J. Stoessl, “Dopamine D1 Receptor Agonist Induced Grooming Is Blocked by the Opiod Receptor Antagonist Maloxone,” European Journal of Pharmacology, Vol. 259, No. 3, 1996, pp. 301-303.
[33] J. Komorowska and S. M. Pellis, “Regulatory Mechanisms Underlying Novelty-Induced Grooming in the Laboratory rat,” Behavioural Processes, Vol. 67, No. 2, 2004, pp. 287-293.
[34] C. D. Conrad, K. A. Grote, R. J. Hobbs and A. Ferayorni, “Sex Differences in Spatial and Non-Spatial Y-Maze Performance after Chronic Stress,” Neurobiology of Learning and Memory, Vol. 79, 200, pp. 32-40.
[35] S. K. Kulkarni, “Handbook of Experimental Pharmacology,” 3rd Edition, Vallabh Prakashan, Delhi, 2005.
[36] N. P. Murphy, H. A. Lam and N. T. Maidment, “A Comparison of Morphine-Induced Locomotor Activity and Mesolimbic Dopamine Release in C57BL6, 129Sv and DBA2 Mice,” Journal of Neurochemistry, Vol. 79, No. 3, 2001, pp. 626-635.
[37] G. Porras, P. DeDeurwaerdere, D. Moison and U. Spampinato, “Conditional Involvement of Striatal Serotonin3 Receptors in the Control of in Vivo Dopamine Outflow in the Rat Striatum,” The European Journal of Neuroscience, Vol. 17, No. 4, 2003, pp. 771-781.

Copyright © 2023 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.