Volume 9, Issue 4, July 2020, Page: 99-107
Effects of Separate and Combined Chronic Ingestion of Codeine and Tramadol on Exploratory Learning Behaviour Among Male Albino Rats
Shyngle Kolawole Balogun, Department of Psychology, Faculty of the Social Sciences, University of Ibadan, Ibadan, Nigeria
Jackson Iheukwumere Osuh, Department of Psychology, Faculty of Social Sciences, Federal University, Oye-Ekiti, Nigeria
Oluwatosi Olatunde Olotu, Department of Psychology, Faculty of the Social Sciences, University of Ibadan, Ibadan, Nigeria
Received: Jun. 24, 2020;       Accepted: Jul. 9, 2020;       Published: Jul. 17, 2020
DOI: 10.11648/j.ajap.20200904.13      View  127      Downloads  69
Tramadol and codeine are opioids known to have effective analgesic effects and potentials for the possible development of tolerance and addiction. The recent increase in the use and abuse of these substances coupled with research evidence implicating the ability of these opioids to readily access opioid receptors in the central nervous system (CNS) is a source of research concern. This study, therefore, examined the effects of chronic exposure to codeine and tramadol on exploratory learning behaviour. Twenty-four (24) male albino rats weighing between 150-200g and 4-6 weeks old, collected from the University of Ibadan Veterinary animal farm were used for this study. They were divided into 4 experimental groups of codeine, tramadol, combined codeine and tramadol and control groups with 6 rats in each group. They were exposed to 8mg/kg of codeine, 20mg/kg of tramadol, combined 8mg/kg of codeine and 20mg/kg of tramadol, and normal saline for the codeine, tramadol, combined codeine and tramadol and control groups respectively for 28 days. The rats were administered with the drugs every other day and observed after each treatment day for exploratory learning behaviour using the T-maze. randomized block ANOVA showed a significant effect of codeine and tramadol on exploratory learning behaviour among male albino rats, f (3,67) = 19.08, p < 0.001, η2=.08. Male albino rats in the codeine treatment group significantly took more time exploring the maze (Mean = 176.64) than combined group (Mean =168.13), tramadol group (Mean =131.10) and control group (Mean =92.48). The mean differences were significant (p<.001). It was concluded that chronic exposure to tramadol and codeine has implications for exploratory learning and memory deficits.
Exploratory Learning Behavior, Codeine, Tramadol, Male Albino Rats
To cite this article
Shyngle Kolawole Balogun, Jackson Iheukwumere Osuh, Oluwatosi Olatunde Olotu, Effects of Separate and Combined Chronic Ingestion of Codeine and Tramadol on Exploratory Learning Behaviour Among Male Albino Rats, American Journal of Applied Psychology. Vol. 9, No. 4, 2020, pp. 99-107. doi: 10.11648/j.ajap.20200904.13
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Jentsch, J. D., & Taylor, J. R. (1999). Impulsivity resulting from frontostriatal dysfunction in drug abuse: Implications for the control of behavior by reward-related stimuli. In Psychopharmacology (Vol. 146, Issue 4, pp. 373–390). https://doi.org/10.1007/PL00005483
Everitt, B. J., & Robbins, T. W. (2005). Neural systems of reinforcement for drug addiction: From actions to habits to compulsion. In Nature Neuroscience (Vol. 8, Issue 11, pp. 1481–1489). https://doi.org/10.1038/nn1579
Sipahi, A., Satilmis, S., & Basa, S. (2015). Comparative study in patients with symptomatic internalderangements of the temporomandibular joint: Analgesicoutcomes of arthrocentesis with or without intra-articularmorphine and tramadol. British Journal of Oral and Maxillofacial Surgery, 53 (4), 316–320. https://doi.org/10.1016/j.bjoms.2014.12.018 LK - http://sfx.hul.harvard.edu/sfx_local?sid=EMBASE&issn=15321940&id=doi:10.1016%2Fj.bjoms.2014.12.018&atitle=Comparative+study+in+patients+with+symptomatic+internalderangements+of+the+temporomandibular+joint%3A+Analgesicoutcomes+of+arthrocentesis+with+or+without+intra-articularmorphine+and+tramadol&stitle=Br.+J.+Oral+Maxillofac.+Surg.&title=British+Journal+of+Oral+and+Maxillofacial+Surgery&volume=53&issue=4&spage=316&epage=320&aulast=Sipahi&aufirst=A.&auinit=A.&auf
Caspani, O., Reitz, M. C., Ceci, A., Kremer, A., & Treede, R. D. (2014). Tramadol reduces anxiety-related and depression-associated behaviors presumably induced by pain in the chronic constriction injury model of neuropathic pain in rats. Pharmacology Biochemistry and Behavior, 124, 290–296. https://doi.org/10.1016/j.pbb.2014.06.018
Faron-Górecka, A., Kuśmider, M., Inan, S. Y., Siwanowicz, J., & Dziedzicka-Wasylewska, M. (2004). Effects of tramadol on α2-adrenergic receptors in the rat brain. Brain Research, 1016 (2), 263–267. https://doi.org/10.1016/j.brainres.2004.05.026
Gopalraju, P., Lalitha, R. M., Prasad, K., & Ranganath, K. (2014). Comparative study of intravenous Tramadol versus Ketorolac for preventing postoperative pain after third molar surgery - A prospective randomized study. Journal of Cranio-Maxillofacial Surgery, 42 (5), 629–633. https://doi.org/10.1016/j.jcms.2013.09.004
Lofwall, M. R., Babalonis, S., Nuzzo, P. A., Siegel, A., Campbell, C., & Walsh, S. L. (2013). Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: A two-phase randomized controlled trial *. Drug Alcohol Depend, 133 (1), 188–197. https://doi.org/10.1016/j.drugalcdep.2013.05.010
Fawzi, M. M. (2011). Some medicolegal aspects concerning tramadol abuse: The new Middle East youth plague 2010. An Egyptian overview | Elsevier Enhanced Reader. Egyptian Journal of Forensic Sciences, 99–102. https://reader.elsevier.com/reader/sd/pii/S2090536X1100030X?token=E929716E3BE86D1F0BF597C94413DA2B670EB6ADE340FBD7474ADBA8C0C1369BACA0331895AF3F0ECD7C043277DA7C1C
Seifi, M., Hassanpour Moghadam, M., Hadizadeh, F., Ali-Asgari, S., Aboli, J., & Mohajeri, S. A. (2014). Preparation and study of tramadol imprinted micro-and nanoparticles by precipitation polymerization: Microwave irradiation and conventional heating method. International Journal of Pharmaceutics, 471 (1–2), 37–44. https://doi.org/10.1016/j.ijpharm.2014.04.071
(WHO), W. H. O. (2017). WHO Expert Committee on Drug Dependence Thirty-ninth report. http://www.
Derry, S., Karlin, S. M., & Moore, R. A. (2013). Single dose oral ibuprofen plus codeine for acute postoperative pain in adults. In R. A. Moore (Ed.), Cochrane Database of Systematic Reviews (Vol. 2013, Issue 3). John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD010107.pub2
Nielsen, S., & Van Hout, M. C. (2017). Over-the-Counter Codeine-from Therapeutic Use to Dependence, and the Grey Areas in Between. Current Topics in Behavioral Neurosciences, 34, 59–75. https://doi.org/10.1007/7854_2015_422
Cooper, R. (2011). ’Respectable Addiction’-A qualitative study of over the counter medicine abuse in the UK.
Cooper, R. J. (2013). Over-the-counter medicine abuse-a review of the literature. Journal of Substance Use, 18 (2), 82–107. https://doi.org/10.3109/14659891.2011.615002
Nations, U., & Narcotics Control Board, I. (2012). 2011 INTERNATIONAL NARCOTICS CONTROL BOARD Report EMBARGO CAUTION UNITED NATIONS. www.incb.org
Robinson, G. M., Robinson, S. McCarthy, P., & Cameron, C. (2010). Misuse of over-the counter codeine.containing analgesics: Dependence and and other adverse effects. New Medical Journal, 123 (1317)
Washington Post (2018) Nigeria's ban on codeine cough syrups could spur Black Market ifDemand not addressed. The Henry J. Kaiser FamilyFoundation. https;//www.kff.org/news-summary/nigerians-ban-on-codeine-cough-syrup.could-spur-black-market-if-demand-not-addressed/
Kelley, A. E. (2004). Memory and addiction: Shared neural circuitry and molecular mechanisms. In Neuron (Vol. 44, Issue 1, pp. 161–179). Cell Press. https://doi.org/10.1016/j.neuron.2004.09.016
Schultz, W. (2010). Open Access REVIEW BioMed Central Dopamine signals for reward value and risk: basic and recent data. https://doi.org/10.1186/1744-9081-6-24
Jay, T. M. (2003). Dopamine: A potential substrate for synaptic plasticity and memory mechanisms. In Progress in Neurobiology (Vol. 69, Issue 6, pp. 375–390). Elsevier Ltd. https://doi.org/10.1016/S0301-0082(03)00085-6
Kalivas, P. (2004). Glutamate systems in cocaine addiction. Current Opinion in Pharmacology, 4 (1), 23–29. https://doi.org/10.1016/j.coph.2003.11.002
Abdolmohamadi, K., Ahmadi, E., Ghadiri, F., Abadi, S., Mohammadzadeh, A., & Yousefzadeh, B. (2019). Downloaded from frooyesh.ir at 19:21 +0430 on Thursday (Vol. 8, Issue 5).
Stefani, M. R., Groth, K., & Moghaddam, B. (2003). Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability. Behavioral Neuroscience, 117 (4), 728–737. https://doi.org/10.1037/0735-7044.117.4.728
Hosseini-Sharifabad, Ali, Ghahremani, M. H., Sabzevari, O., Naghdi, N., Abdollahi, M., Beyer, C., Bollen, E., Prickaerts, J., Roghani, A., & Sharifzadeh, M. (2012). Effects of protein kinase A and G inhibitors on hippocampal cholinergic markers expressions in rolipram- and sildenafil-induced spatial memory improvement. Pharmacology Biochemistry and Behavior, 101 (3), 311–319. https://doi.org/10.1016/j.pbb.2012.01.017
Sardari, M., Rezayof, A., Khodagholi, F., & Zarrindast, M. R. (2014). Basolateral amygdala GABA-A receptors mediate stress-induced memory retrieval impairment in rats. International Journal of Neuropsychopharmacology, 17 (4), 603–612. https://doi.org/10.1017/S1461145713001363
Makkar, S. R., Zhang, S. Q., & Cranney, J. (2010). Behavioral and neural analysis of GABA in the acquisition, consolidation, reconsolidation, and extinction of fear memory. In Neuropsychopharmacology (Vol. 35, Issue 8, pp. 1625–1652). Nature Publishing Group. https://doi.org/10.1038/npp.2010.53
Hritcu, L., Clicinschi, M., & Nabeshima, T. (2007). Brain serotonin depletion impairs short-term memory, but not long-term memory in rats. Physiology and Behavior, 91 (5), 652–657. https://doi.org/10.1016/j.physbeh.2007.03.028
Chavant, F., Favrelière, S., Lafay-Chebassier, C., Plazanet, C., & Pérault-Pochat, M. C. (2011). Memory disorders associated with consumption of drugs: Updating through a case/noncase study in the French PharmacoVigilance Database. British Journal of Clinical Pharmacology, 72 (6), 898–904. https://doi.org/10.1111/j.1365-2125.2011.04009.x
Abdel-Ghany, R., Nabil, M., Abdel-Aal, M., & Barakat, W. (2015). Nalbuphine could decrease the rewarding effect induced by tramadol in mice while enhancing its antinociceptive activity. European Journal of Pharmacology, 758, 11–15. https://doi.org/10.1016/j.ejphar.2015.03.062
Spain, J. W., & Newsom, G. C. (1991a). Chronic opioids impair acquisition of both radial maze and Y-maze choice escape. Psychopharmacology, 105 (1), 101–106. https://doi.org/10.1007/BF02316870
Jesse, C. R., Bortolatto, C. F., Savegnago, L., Rocha, J. B. T., & Nogueira, C. W. (2008). Involvement of l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 32 (8), 1838–1843. https://doi.org/10.1016/j.pnpbp.2008.08.010
Nava-Mesa, M. O., Lamprea, M. R., & Múnera, A. (2013). Divergent short- and long-term effects of acute stress in object recognition memory are mediated by endogenous opioid system activation. Neurobiology of Learning and Memory, 106, 185–192. https://doi.org/10.1016/j.nlm.2013.09.002
Ng, K. F. J., Yuen, T. S. T., & Ng, V. M. W. (2006). A comparison of postoperative cognitive function and pain relief with fentanyl or tramadol patient-controlled analgesia. Journal of Clinical Anesthesia, 18 (3), 205–210. https://doi.org/10.1016/j.jclinane.2005.08.004
Hosseini-Sharifabad, A, Rabban, S., Sharifzadeh, M., & Bagheri, N. (2016). Acute and chronic tramadol administration impair spatial memory in rat. Research in Pharmaceutical Sciences, 11 (1), 49–57.
Hadad, S., & Assistant, M. (2018). Attention and Memory in Tramadol Addiction. In SOHAG MEDICAL JOURNAL (Vol. 22, Issue 3). www.pdffactory.com
National Research Council (2011) GUIDE FOR LABORATORY ANIMALS FOR THE CARE AND USE OF ANIMALS. Eight Edition Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Institute for LaboratoryAnimal Research Division on Earth animal studies. htpp://www.nap.edu
Uwadiegwu Achukwu, P., Terry Omorodion, N., Tosan, E., aloh, H. E., Charles, E., & Ome, O. (2019). Codeine and its Histopathological Effect on Brain of Albino Rats: An Experimental Study.
Lee, E. Y., Lee, E. B., Park, B. J., Lee, C. K., Yoo, B., Lim, M. K., Shim, S. C., Sheen, D. H., Seo, Y., Ah Kim, H., Baek, H. J., & Song, Y. W. (2006). Tramadol 37.5-mg/acetaminophen 325-mg combination tablets added to regular therapy for rheumatoid arthritis pain: A 1-Week, randomized, double-blind, placebo-controlled trial. Clinical Therapeutics, 28 (12), 2052–2060. https://doi.org/10.1016/j.clinthera.2006.12.019
Vaseghi, G., Rabbani, M., & Hajhashemi, V. (2013). The effect of AM281, a cannabinoid antagonist, on memory performance during spontaneous morphine withdrawal in mice. Research in Pharmaceutical Sciences, 8 (1), 59.
Benini, F., & Barbi, E. (2014). Doing without codeine: why and what are the alternatives? https://doi.org/10.1186/1824-7288-40-16.
Xie, R., & Hammarlund-Udenaes, M. (1998). Blood-brain barrier equilibration of codeine in rats studied with microdialysis. Pharmaceutical Research, 15 (4), 570–575. https://doi.org/10.1023/A:1011929910782
Hau, V. S., Huber, J. D., Campos, C. R., Davis, R. T., & Davis, T. P. (2004). Effect of λ-carrageenan-induced inflammatory pain on brain uptake of codeine and antinociception. Brain Research, 1018 (2), 257–264. https://doi.org/10.1016/j.brainres.2004.05.081
Birthelmer, A., Stemmelin, J., Jackisch, R., & Cassel, J. C. (2003). Presynaptic modulation of acetylcholine, noradrenaline, and serotonin release in the hippocampus of aged rats with various levels of memory impairments. Brain Research Bulletin, 60 (3), 283–296. https://doi.org/10.1016/S0361-9230(03)00042-X
Dubrovina, N. I., & Ilyutchenok, R. Y. (1996). Dopamine and opioid regulation of the memory retrieval recovery in mice. Behavioural Brain Research, 79 (1–2), 23–29. https://doi.org/10.1016/0166-4328(95)00258-8
Ghamati, L., Hajali, V., Sheibani, V., Esmaeilpour, K., Sepehri, G., & Shojaee, M. (2014). Single and repeated ultra-rapid detoxification prevents cognitive impairment in morphine addicted rats: a privilege for single detoxification. Addiction & Health, 6 (1–2), 54–64. http://www.ncbi.nlm.nih.gov/pubmed/25140218
Mackintosh, N. J. (1975). A theory of attention: Variations in the associability of stimuli with reinforcement. Psychological Review, 82 (4), 276–298. https://doi.org/10.1037/h0076778
Baghishani, F., Mohammadipour, A., Hosseinzadeh, H., Hosseini, M., & Ebrahimzadeh-bideskan, A. (2018). The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin. Metabolic Brain Disease, 33 (3), 907–916. https://doi.org/10.1007/s11011-018-0194-6
Zhuo, H. Q., Huang, L., Huang, H. Q., & Cai, Z. (2012). Effects of chronic tramadol exposure on the zebrafish brain: A proteomic study. Journal of Proteomics, 75 (11), 3351–3364. https://doi.org/10.1016/j.jprot.2012.03.038
Ghoneim, F. M., Khalaf, H. A., Elsamanoudy, A. Z., & Helaly, A. N. (2014). Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: Histological, immunohistochemical and biochemical study. International Journal of Clinical and Experimental Pathology, 7 (11), 7323–7341.
Boostani, R., & Derakhshan, S. (2012). Tramadol induced seizure: A 3-year study. Caspian Journal of Internal Medicine, 3 (3), 484–487.
Hussein, S. A., Samir,;, Latif, A., Aal, A., & Ismail, H. K. (2017). Neurodegeneration and oxidative stress induced by tramadol administration in male rats: The effect of its withdrawal. http://www.bvmj.bu.edu.eg
Candeletti, S., Lopetuso, G., Cannarsa, R., Cavina, C., & Romualdi, P. (2006). Effects of prolonged treatment with the opiate tramadol on prodynorphin gene expression in rat CNS. Journal of Molecular Neuroscience, 30 (3), 341–347. https://doi.org/10.1385/JMN:30:3:341
Kim, E. J., Pellman, B., & Kim, J. J. (2015). Stress effects on the hippocampus: A critical review. In Learning and Memory (Vol. 22, Issue 9, pp. 411–416). Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/lm.037291.114
Chieffi, S., Messina, G., Villano, I., Messina, A., Esposito, M., Monda, V., Valenzano, A., Moscatelli, F., Esposito, T., Carotenuto, M., Viggiano, A., Cibelli, G., & Monda, M. (2017). Exercise influence on hippocampal function: Possible involvement of orexin-a. Frontiers in Physiology, 8, 85. https://doi.org/10.3389/fphys.2017.00085
Rajabian, A., Hosseini, A., Hosseini, M., & Sadeghnia, H. R. (2019). A review of potential efficacy of saffron (Crocus sativus L.) in cognitive dysfunction and seizures. In Preventive Nutrition and Food Science (Vol. 24, Issue 4, pp. 363–372). Korean Society of Food Science and Nutrition. https://doi.org/10.3746/pnf.2019.24.4.363
Zarrindast, M. R., Hoghooghi, V., & Rezayof, A. (2008). Inhibition of morphine-induced amnesia in morphine-sensitized mice: Involvement of dorsal hippocampal GABAergic receptors. Neuropharmacology, 54 (3), 569–576. https://doi.org/10.1016/j.neuropharm.2007.11.004
Kouwenberg, A.-L., Martin, G. M., Skinner, D. M., Thorpe, C. M., & Walsh, C. J. (2012). Spontaneous Object Recognition in Animals: A Test of Episodic Memory. www.intechopen.com
Rabbani, M., Hajhashemi, V., & Mesripour, A. (2009). Increase in brain corticosterone concentration and recognition memory impairment following morphine withdrawal in mice. Stress, 12 (5), 451–456. https://doi.org/10.1080/10253890802659612
Darke, S., Sims, J., McDonald, S., & Wickes, W. (2000). Cognitive impairment among methadone maintenance patients. Addiction, 95 (5), 687–695. https://doi.org/10.1046/j.1360-0443.2000.9556874.x
Davis, P. E., Liddiard, H., & McMillan, T. M. (2002). Neuropsychological deficits and opiate abuse. Drug and Alcohol Dependence, 67 (1), 105–108. https://doi.org/10.1016/S0376-8716(02)00012-1
Curran, H. V., Kleckham, J., Bearn, J., Strang, J., & Wanigaratne, S. (2001). Effects of methadone on cognition, mood and craving in detoxifying opiate addicts: A dose-response study. Psychopharmacology, 154 (2), 153–160. https://doi.org/10.1007/s002130000628
Ornstein, T. J., Iddon, J. L., Baldacchino, A. M., Sahakian, B. J., London, M., Everitt, B. J., & Robbins, T. W. (2000). Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology, 23 (2), 113–126. https://doi.org/10.1016/S0893-133X(00)00097-X
Eisch, A. J., Barrot, M., Schad, C. A., Self, D. W., & Nestler, E. J. (2000). Opiates inhibit neurogenesis in the adult rat hippocampus. www.pnas.orgcgidoi10.1073pnas.120552597
Farahmandfar, M., Karimian, S. M., Naghdi, N., Zarrindast, M. R., & Kadivar, M. (2010). Morphine-induced impairment of spatial memory acquisition reversed by morphine sensitization in rats. Behavioural Brain Research, 211 (2), 156–163. https://doi.org/10.1016/j.bbr.2010.03.013
Ma, M. X., Chen, Y. M., He, J., Zeng, T., & Wang, J. H. (2007). Effects of morphine and its withdrawal on Y-maze spatial recognition memory in mice. Neuroscience, 147 (4), 1059–1065. https://doi.org/10.1016/j.neuroscience.2007.05.020
Spain, J. W., & Newsom, G. C. (1991b). Chronic opioids impair acquisition of both radial maze and Y-maze choice escape. Psychopharmacology, 105 (1), 101–106. https://doi.org/10.1007/BF02316870
Retailleau, A., Dejean, C., Fourneaux, B., Leinekugel, X., & Boraud, T. (2013). Why am I lost without dopamine? Effects of 6-OHDA lesion on the encoding of reward and decision process in CA3. Neurobiology of Disease, 59, 151–164. https://doi.org/10.1016/j.nbd.2013.07.014
Papich, M. G. (2016). Codeine. In Saunders Handbook of Veterinary Drugs (pp. 183–184). Elsevier. https://doi.org/10.1016/B978-0-323-24485-5.00175-3
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