Caffeine is the most widely consumed psychoactive drug in the world, ingested as natural components of chocolate, coffee and tea and as added components to soda and energy drinks. Here we assessed behavioural changes caused by chronic caffeine administration as well as morphological changes within specific regions of the adult mice brain: the hippocampus and amygdala. Twenty-four adult male albino mice were randomly divided into three groups. Caffeine was administered daily by gavage for 8 weeks at a dosage of 20 mg/kg for low dose (LD) group and 60 mg/kg for high dose (HD) group while the third group served as control (CNT). After the period of administration, neurobehavioural tasks were carried out; Morris water maze for learning and memory open field test and elevated plus maze test for anxiety. The mice were sacrificed; their brain tissues were harvested and processed for H&E, Cresyl violet and Golgi staining, and assessed qualitatively and quantitatively. Quantitative data from the neurobehavioural tests and neuronal cell counts were expressed as means ± standard errors of means and compared across the groups using analysis of variance (ANOVA). Significance was set at p< 0.05.
Mice in the high dose group learnt faster and had significantly increased number of platform crossings in the Morris water maze test. There was, however, a slightly increased level of anxiety in the caffeine-treated mice, compared to controls. Histo-morphometric analysis revealed significantly increased number of pyramidal neurons in the hippocampus in the low dose group, but a decreased neuronal count in the amydala of the low dose and high dose groups compared to controls. The pyramidal neurons in the hippocampus of the caffeine-treated mice had increased apical dendritic length compared to the controls. Our findings strengthen the available data suggesting that prolonged caffeine intake improves cognition, and this process could be mediated by promoting the growth of dendrites and increased number of neurons. However, this is coupled with an increased tendency to be anxiogenic.
Alhaider, I.A., Aleisa, M.A., Tran, T.T., Alzoubi, K.H.and Alkadhi, A.K. 2010. Chronic caffeine treatment prevents sleep deprivation-induced impairment of cognitive function and synaptic plasticity. Sleep 33:437–444.
Almosawi, S., Baksh, H. Qareeballa, A., Falamarzi, F., Alsaleh, B., Alrabaani, M., Alkalbani, A., Mahdi, S. and Kamal, A. 2018. Acute Administration of Caffeine: The Effect on Motor Coordination, Higher Brain Cognitive Functions, and the Social Behavior of BLC57 Mice. Behavioural Science. 8, 65.
Angelucci, M.E.M., Cesário, C., Hiroi, Rosalen, P.L. and C. da Cunha, C. 2002. Effects of caffeine on learning and memory in rats tested in the Morris water maze. Brazilian Journal of Medical and Biological Research 35: 1201-1208
Antonioua, K., Kafetzopoulosa, E., Papadopoulou-Daifotib, Z., Hyphantisa, T. and Marselos, M. 1998. d-amphetamine, cocaine and caffeine: a comparative study of acute effects on locomotor activity and behavioural patterns in rats. Neuroscience and Biobehavioral Reviews 23; 189–196
Ardais AP, Borges MF, Rocha AS, Sallaberry C, Cunha RA, Porciuncula LO. Caffeine triggers behavioral and neurochemical alterations in adolescent rats. Neuroscience. 2014; 270:27–39. [PubMed: 24726984]
Dunwiddie, T. V. and Masino, S. A. 2001. The role and regulation of adenosine in the central nervous system. Annual Review of Neuroscience. 24: 31–55
Ekong, M.B., Kingsley A. Okon, K.A., and Muonagolu. N.J. 2017. Effect of Caffeine on Body Weight and Hippocampal Cells in a Murine Model. The Pharmaceutical and Chemical Journal, 4(5):174-181
El Yacoubi, M., Ledent, C., MeÂnard, J.F., Parmentier, M., Costentin, J. and Vaugeois, J.M. 2000. The stimulant effects of caffeine on locomotor behaviour in mice are mediated through its blockade of adenosine A2A receptors. British Journal of Pharmacology 129, 1465 ± 147
Fredholm BB, Bättig K, Holmén J, Nehlig A, Zvartau EE. Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev. 1999 Mar;51(1):83-133.
Gökcen, B.B., Şanlier, N. (2019). Coffee consumption and disease correlations. Critical Reviews in Food Science and Nutrition. 59(2):336-348. doi: 10.1080/10408398.2017. 1369391. Epub 2017 Sep 29
Han, M.E., Park, K.H., Baek, S.Y., Kim, B.S., Kim, J.B., Kim, H.J. and Oh, S.O. 2007. Inhibitory effects of caffeine on hippocampal neurogenesis and function. Biochemical and Biophysical Research Communications. 356 (2007) 976–980
Henigsberg, N., Kalember, P., Petrovic, Z. K., and Secic, A. 2019. Neuroimaging research in posttraumatic stress disorder - Focus on amygdala, hippocampus and prefrontal cortex. Progress in Neurosychopharmacology, Biology and Psychiatry 90, 37–42. doi: 10.1016/j.pnpbp.2018.11.003
Him, A., Deniz, B.N. and Onger, M.E. 2018. The effect of caffeine on neuron number of rats exposed to 900-MHz electromagnetic field. Turkish Journal of Veterinary and Animal Sciences. (2018) 42: 198-204 © TÜBİTAK doi:10.3906/vet-1802-31
Kim, T.W., Shin, Y.O., Lee, J.B., Min, Y.K., Yang, H.M., 2011. Caffeine increases sweating sensitivity via changes in sudomotor activity during physical loading. J. Med. Food 14, 1448–1455
Kolahdouzan, M. and Hamadeh, M.J. (2017). The neuroprotective effects of caffeine in neurodegenerative diseases. Central Nervous System Neuroscience and Therapeutics. 23(4):272-290
Lanini J, Galduróz JC, Pompéia S. (2016). Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions. Hum Psychopharmacol. 31(1):29-43.
Mahdi S, Almosawi S, Baksh H, et al. Effect of chronic administration and withdrawal of caffeine on motor function, cognitive functions, anxiety, and the social behavior of BLC57 mice. Int J Health Sci (Qassim). 2019;13(2):10-16.
Noschang, C.G., Krolow, R., Pettenuzza, L.F., Avila, M.C. and Faschin, A. 2009. Interaction between chronic stress and chronic comsumption of caffeine on the enzymatic antioxidant system. Neurochemical Research. 34;1508-74, http://dx.doi.org/10.1007/s11064-009-9945-4.
Olopade, F.E. and Shokunbi, M.T. 2016. Neurobehavioral Deficits in Progressive Experimental Hydrocephalus in Neonatal Rats. Nigerian Journal of Physiology and Science. 31 :105-113
Olopade, F.E. and Shokunbi, M.T. (2018). The development of the external granular layer of the
cerebellum and neurobehavioral correlates in neonatal rats following intrauterine and
postnatal exposure to caffeine. Journal of Caffeine and Adenosine Research. 8 (1), 27-36.
Pechlivanova, D.M., Tchekalarova, J.D., Alova, L.H., Petkov, V.V., Nikolov, R.P. and Yakimova, K.S. 2012. Effect of long-term caffeine administration on depressive-like behavior in rats exposed to chronic unpredictable stress. Behavioural Pharmacology. 4 (2012).
Pellow, S., Chopin, P., File, S.E, and Briley, M. 1985. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. Journal of Neuroscience Methods 14:149–167.
Ribeiro., J. A., Sebastiao,. A. M. and de Mendonca, A. 2002. Adenosine receptors in the nervous system: pathophysiological implications. Progress in Neurobiology 68(6): 377-92
Ribeiro JA, Sebastiao AM, de Mendonca A. Participation of adenosine receptors in neuroprotection. Drug News Perspect. 2003 Mar;16(2):80-6. doi: 10.1358/dnp.2003.16.2.740246
Ruxton CH. The suitability of caffeinated drinks for children: a systematic review of randomised controlled trials, observational studies and expert panel guidelines. J Hum Nutr Diet. 2014; 27:342–357. [PubMed: 25099503]
Sallaberry, C., Nunes, F., Marcelo S. Costa, M.S., Gabriela T. Fioreze, T.G., Ardais, A.P., Henrique, P., Botton. S., Klaudat, Forte, T.B., Souza, O.D., Elisabetsky, E. and Porciúncula, O.L. 2013. Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rat. Neuropharmacology 64 (2013) 153-159.
Stafford, L.D., Rusted, J., Yeomans, M.R., 2007. Caffeine, mood, and performance. A selective review. In: Smith, B.D., Gupta, U., Gupta, B.S. (Eds.), Caffeine and Activation Theory: Effects on Health and Behavior. Taylor and Francis, Boca Raton, FL, pp. 284–310.
Toschi, N., Duggento, A., and Passamonti, L. 2017. Functional connectivity in amygdalar-sensory/ (pre)motor networks at rest: new evidence from the Human Connectome Project. European Journal of Neuroscience. 45, 1224–1229. doi: 10.1111/ejn.13544
Trapp GS, Allen K, O’Sullivan TA, Robinson M, Jacoby P, Oddy WH. Energy drink consumption is associated with anxiety in Australian young adult males. Depress Anxiety. 2014; 31:420–428. [PubMed: 24019267]
Vila-Luna, S., Cabrera-Isidoro, S., Vila-Luna, L., JuarezDiaz, I., Bata-Garcia, J.L. and Alvarez-Cervera, F.J. 2012. Chronic caffeine consumption prevents cognitive decline from young to middle age in rats, and is associated with increased length, branching, and spine density of basal dendrites in CA1 hippocampal neurons. Neuroscience. 202:384–395.
Vriend, C., Boedhoe, P. S., Rutten, S., Berendse, H. W., van der Werf, Y. D., and van den Heuvel, O. A. 2016. A smaller amygdala is associated with anxiety in Parkinson’s disease: a combined FreeSurfer-VBM study. Journal of Neurology and Neurosurgery Psychiatry 87, 493–500. doi: 10.1136/jnnp-2015-310383
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