Effects of the Combination of Caffeine, Nicotine, and 3,4 Methylenedioxymethamphetamine (MDMA) on the Hippocampus of Experimental Wistar Rats
Article Sidebar
Main Article Content
Abstract
Caffeine, nicotine, and MDMA are generally referred to as psychoactive substances which contain chemical substances that change the function of the brain and result in alteration of mood, perception, consciousness, cognition, or behavior. These substances are both rewarding and positively reinforcing which indicates a potential for inducing addiction. The hippocampus is an important part of the brain whose primary function is learning and memory. This study aimed to investigate the impact of combining caffeine, nicotine, and MDMA on the hippocampus of Wistar rats. A total of 32 Wistar rats were randomly divided into four groups, each consisting of eight animals. Group A served as the control and received normal saline (2 ml/kg.bw). Group B received a combination of caffeine (100 mg/kg) and nicotine (50 mg/kg), Group C received a combination of caffeine (100 mg/kg) and MDMA (10 mg/kg), and Group D received a combination of nicotine (50 mg/kg) and MDMA (10 mg/kg). The administration of substances continued for a duration of 21 days. The result showed that there was a significant increase in the level of neurotransmitters, Neuroarchitecture using different staining techniques and neurostructural changes were observed on the hippocampus, especially in the dentate gyrus across the co-administered groups. The co-administration of caffeine, nicotine, and MDMA did not cause any extensive hippocampal degeneration or localized neurodegeneration, however, there was an increase in the number of cells in the dentate gyrus which suggested a possible neurogenesis. Neurobehavioural analysis showed impairment in learning and memory.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Hammer GD, McPhee SJ. Pathophysiology of Disease: An Introduction to Clinical Medicine. 8th ed. New York: Lange; 2010. pp. 232-320
Kota D, Robinson SE, Imad Damaj M. Enhanced nicotine reward in adulthood after exposure to nicotine during early adolescence in mice. Biochem Pharmacol. 2009; 78(7):873-9.
Freye E. Pharmacological Effects of MDMA in Man. In: Pharmacology and Abuse of Cocaine, Amphetamines, Ecstasy and Related Designer Drugs. Springer; 2009.
Sheikholeslami B, Tootoonchi Z, Lavasani H, Hosseinzadeh Ardakani Y, Rouini M. Investigation of MDMA Inhibitory Effect on CytochromeP450 3A4 in Isolated Perfused Rat Liver Model Using Tramadol. Adv Pharm Bull. 202; 11(3):530-536.
Daly JW, Holmén J, Fredholm BB. Ar koffein beroendeframkallande? Världens mest nyttjade psykoaktiva substans påverkar samma delar av hjärnan som kokain [Is caffeine addictive? The most widely used psychoactive substance in the world affects same parts of the brain as cocaine]. Lakartidningen. 1998; 95(51-52):5878-83.
Doss MK, de Wit H, Gallo DA. The acute effects of psychoactive drugs on emotional episodic memory encoding, consolidation, and retrieval: A comprehensive review. Neurosci Biobehav Rev. 2023; 150:105188.
Gouzoulis-Mayfrank E, Daumann J. Neurotoxicity of methylenedioxyamphetamines (MDMA; ecstasy) in humans: how strong is the evidence for persistent brain damage? Addiction. 2006; 101(3):348-61.
Costa MS, Botton PH, Mioranzza S, Souza DO, Porciúncula LO. Caffeine prevents age-associated recognition memory decline and changes brain-derived neurotrophic factor and tirosine kinase receptor (TrkB) content in mice. Neuroscience. 2008; 153(4):1071-8.
Carter AJ, O'Connor WT, Carter MJ, Ungerstedt U. Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors. J Pharmacol Exp Ther. 1995; 273(2):637-42.
Trauth JA, Seidler FJ, McCook EC, Slotkin TA. Adolescent nicotine exposure causes persistent upregulation of nicotinic cholinergic receptors in rat brain regions. Brain Res. 1999; 851(1-2):9-19.
Halpin LE, Collins SA, Yamamoto BK. Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine. Life Sci. 2014; 97(1):37-44.
Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L. Toxicity of amphetamines: an update. Arch Toxicol. 2012; 86(8):1167-231.
Chakraborty R, Vepuri V, Mhatre SD, Paddock BE, Miller S, Michelson SJ, Delvadia R, Desai A, Vinokur M, Melicharek DJ, Utreja S, Khandelwal P, Ansaloni S, Goldstein LE, Moir RD, Lee JC, Tabb LP, Saunders AJ, Marenda DR. Characterization of a Drosophila Alzheimer's disease model: pharmacological rescue of cognitive defects. PLoS One. 2011; 6(6):e20799.
Ulusu U, Uzbay IT, Kayir H, Alici T, Karakas S. Evidence for the role of nitric oxide in nicotine-induced locomotor sensitization in mice. Psychopharmacology (Berl). 2005; 178(4):500-4.
Adeniyi PA, Ishola AO, Laoye BJ, Olatunji BP, Bankole OO, Shallie PD, Ogundele OM. Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment. Metab Brain Dis. 2016; 31(1):93-107.
Budzynska B, Wnorowski A, Kaszubska K, Biala G, Kruk-Słomka M, Kurzepa J, Boguszewska-Czubara A. Acute MDMA and Nicotine Co-administration: Behavioral Effects and Oxidative Stress Processes in Mice. Front Behav Neurosci. 2018; 12:149.
Pubill D, Garcia-Ratés S, Camarasa J, Escubedo E. Neuronal Nicotinic Receptors as New Targets for 17.Amphetamine-Induced Oxidative Damage and Neurotoxicity. Pharmaceuticals (Basel). 2011; 4(6):822–47.
Budzynska B, Boguszewska-Czubara A, Kruk-Slomka M, Skalicka-Wozniak K, Michalak A, Musik I, Biala G, Glowniak K. Effects of imperatorin on nicotine-induced anxiety- and memory-related responses and oxidative stress in mice. Physiol Behav. 2013; 122:46-55.
National research council (NRC) 2010.
Walf AA, Frye CA. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat Protoc. 2007; 2(2):322-8.
Pellow S, Chopin P, File SE, Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985; 14(3):149-67.
Harrison FE, Hosseini AH, McDonald MP. Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav Brain Res. 2009; 198(1):247-51.
Wang HR, Woo YS, Bahk WM. Caffeine-induced psychiatric manifestations: a review. Int Clin Psychopharmacol. 2015; 30(4):179-82.
Picciotto MR, Brunzell DH, Caldarone BJ. Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport. 2002;3(9):1097-106.
Anneken JH, Cunningham JI, Collins SA, Yamamoto BK, Gudelsky GA. MDMA increases glutamate release and reduces parvalbumin-positive GABAergic cells in the dorsal hippocampus of the rat: role of cyclooxygenase. J Neuroimmune Pharmacol. 2013; 8(1):58-65.
S Shingo AS, Kito S. Effects of nicotine on neurogenesis and plasticity of hippocampal neurons. J Neural Transm (Vienna). 2005; 112(11):1475-8.
Šlamberová R, Mikulecká A, Macúchová E, Hrebíčková I, Ševčíková M, Nohejlová K, Pometlová M. Effects of psychostimulants on social interaction in adult male rats. Behav Pharmacol. 2015; 26(8 Spec No):776-85.
Pascual M, Pla A, Miñarro J, Guerri C. Neuroimmune activation and myelin changes in adolescent rats exposed to high-dose alcohol and associated cognitive dysfunction: a review with reference to human adolescent drinking. Alcohol. 2014; 49(2):187-92.
Schmued LC. Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA. Brain Res. 2003; 974(1-2):127-33.
Marret S, Gressens P, Van-Maele-Fabry G, Picard J, Evrard P. Caffeine-induced disturbances of early neurogenesis in whole mouse embryo cultures. Brain Res. 1997; 773(1-2):213-6.
Adetunji OA, Adetunji IT, Afolayan S, Akinola OB. Role of Progesterone Treatment on the Microanatomy of the Prefrontal Cortex of Streptozotocin-Induced Diabetic Wistar Rats. Glob J Pharmacol. 2020; 14(1):08-16.