The features of summary background electric activity of the hypothalamus of rats under conditions of chronic caffeine alimentation

  • T. G. Turitskaya Oles Honchar Dnipro National University
  • S. N. Lukashev Regional Clinical Hospital n.a. Mechnikov
  • V. P. Lyashenko Oles Honchar Dnipro National University
  • G. G. Sidorenko Dnipro National University of Railway Ttransport n.a. Academician V. Lazaryan
Keywords: brain activity; trophotropic and ergotropic zone of the hypothalamus; sodium caffeine benzoate; rat; chronic caffeine alimentation


One of the factors of the environment which essentially shifts homeostasis is diets which contain caffeine. The aim of the study was to find out the basic characteristics of background electrical activity of trophotrophic and ergotrophic zones of the hypothalamus in conditions of chronic caffeine alimentation. Experiments were carried out on non-linear white male rats. The first group consisted of control animals (n = 22). The second group (n = 24) was represented by the animals that were given pure caffeine in an amount of 150 mg/kg/day with their meal. The registration on a electrohypothalamogram was carried out in conditions of acute experiment, every 2 weeks for 12 weeks. The spectral (mkV2) and the normalized power (%) of electrohypothalamogram waves were analyzed within the common frequency band. The analysis of the results allowed us to establish a certain specificity of the reaction of the neuronal system of the trophotropic and ergotropic zones of the rat hypothalamus to the effect of chronic caffeine alimentation. The main difference in the reactive state of electrophysiological indices in the trophotrophic zone of rats is the lack of a typical desynchronization from the 4th to the 8th week of the study and the hypersynchronization after 12 weeks of the experiment. The most probable mechanism that explains the results obtained is the ultra-powerful GABA-ergic modulation of this zone, the main energy-accumulating center. Perhaps, this powerful inhibitory resource in this cerebral locus is the main stress-limiting factor that makes this zone of the central nervous system of rats less sensitive to caffeine exposure. Instead, under the influence of chronic caffeine load in the ergotropic zone of the hypothalamus, after 6 weeks of the experiment desynchronous high-frequency rhythms dominated. During the subsequent time of the experiment, we observed a decrease in both low-frequency and high-frequency components of the electrohypothalamogram of this zone. This gives reason to assume that the key component of the neurophysiological response of the posterior hypothalamus of rats to the caffeine ration is the powerful glutamatergic effects on the pre-synaptic and post-synaptic neurons under conditions of reactive exhaustion of local neurosynthetics. Caffeine depletion of the hypothalamic neurotransmission at the end of the experiment is replaced by an effective adaptive ergotropic restoration of neurosynthetic activity in this locus of the central nervous system of rats. Thus, caffeine has a powerful activating effect on the ergotropic function of the posterior hypothalamus of rats. Such a difference in the chronic effect of caffeine on the trophotropic and ergotropic zone of the rat hypothalamus is primarily due to the different mediator support of these zones underlying their physiological purpose. GABA is the main mediator of the trophotropic zone and the main neurotransmitter of its synchronous activity. At the same time, neurotransmitter support of the ergotropic zone is represented by glutamate, which, along with other agents, implements its desynchronous activity. Since caffeine stimulates excitation, activating the pathways traditionally associated with motivational and motor reactions in the brain, it can be assumed that this explains the fact of a more powerful influence of caffeine precisely on the ergotrophic zone of the hypothalamus.


Agadzhanjan, N. A. (1983). Adaptacija i rezervy organizma [Adaptation and body reserves]. Fizkul'tura i Sport, Moscow (in Russian).

Antonelli-Ushirobira, T. M., Kaneshima, E. N., Gabriel, M., Audi, E. A., Marques, L. C., & Mello, J. C. (2010). Acute and subchronic toxicological evaluation of the semipurified extract of seeds of guaraná (Paullinia cupana) in rodents. Food and Chemical Toxicology, 48(7), 1817–1820.

Baldwin, A. L. (2006). Mast cell activation by stress. Methods in Molecular Biology, 315, 349–360.

Bartamesz, V., Aubry, J. M., & Steimer, T. (1994). Stressor-specific increase of vasopressin mRNA in paraventricular hypophysiothrophic neurons. Neuroscience Letters, 170, 35–38.

Battig, K., & Welzl, H. (1993). Psychopharmacological profile of caffeine. In: Garatini, S. (Ed.). Caffeine, coffee and health. Raven Press, New York. Pp. 213–253.

Berthou, F., Goasduff, T., Dréano, Y., & Ménez, J. F. (1995). Caffeine increases its own metabolism through cytochrome P4501A induction in rats. Life Sciences, 57(6), 541–549.

Bunn, C., Läderach, P., Rivera, O. O., & Kirschke, D. (2015). A bitter cup: Climate change profile of global production of Arabica and Robusta coffee. Climatic Change, 129(1–2), 89–101.

Buresh, J., Petran', M., & Zahar, I. (1962). Jelektrofiziologicheskie metody isledovanija [Electrophysiological methods of investigation]. Izdatel’stvo Inostrannoj Literatury, Moscow (in Russian).

Daly, J. W. (2007). Caffeine analogs: Biomedical impact. Cellular and Molecular Life Sciences, 64(16), 2153–2169.

Darlington, D. N., Barraclough, C. A., & Gann, D. S. (1992). Hypotensive hemorrhage elevates corticotrophin-releasing hormone messenger ribonucleic acid (mRNA) but not vasopressin mRNA in the rat hypothalamus. Endocrinology, 130, 1281–1288.

Derimedved', L. V., Percev, I. M., & Shuvalova, E. V. (2001). Vzaimodejstvie lekarstv i jeffektivnost' farmakoterapii [Interaction of drugs and the effectiveness of pharmacotherapy]. Megapolis, Kharkov (in Russian).

Dimpfel, W. (2013). Pharmacological classification of herbal extracts by means of comparison to spectral EEG signatures induced by synthetic drugs in the freely moving rat. The Journal of Ethnopharmacology, 149(2), 583–589.

Echeverri, D., Montes, F. R., Cabrera, M., Galán, A., & Prieto, A. (2010). Caffeine’s vascular mechanisms of action. International Journal of Vascular Medicine, 2010, article ID 834060.

Fernstrom, J. D. (2000). Can nutrient supplements modify brain function? American Journal of Clinical Nutrition, 71(6), 1669S–1675S.

Gasser, P. J., Lowry, C. A., & Orchinik, M. (2006). Corticosterone-sensitive monoamine transport in the rat dorsomedial hypothalamus: Potential role for organic cation transporter 3 in stress-induced modulation of monoaminergic neurotransmission. Journal of Neuroscience, 26(34), 8758–8766.

Geel, L., Kinnear, M., & de Kock, H. L. (2005). Relating consumer preferences to sensory attributes of instant coffee. Food Quality and Preference, 16, 237–244.

Georgiev, V., Johansson, B., & Fredholm, B. B. (1993). Long-term caffeine treatment leads to a decreased susceptibility to NMDA-induced clonic seizures in mice without changes in adenosine A1 receptor number. Brain Research, 612(1–2), 271–277.

Govindwar, S. P., Kachole, M. S., & Pawar, S. S. (1984). In vivo and in vitro effects of caffeine on hepatic mixed-function oxidases in rodents and chicks. Food and Chemical Toxicology, 22(5), 371–375.

Gray, J. (1972). Tne psychology of fear and stress. Academic Press, New York.

Grosso, G., Godos, J., Galvano, F., & Giovannucci, E. L. (2017). Coffee, caffeine, and health outcomes: An umbrella review. The Annual Review of Nutrition, 37, 131–156.

Gunnar, M. R., Herrera, A., & Hostinar, C. E. (2009). Stress and early brain development. Encyclopedia on Early Childhood Development. Centre of Excellence for Early Childhood Development, Montreal, Quebec. Pp. 1–8.

Kalsbeek, A., Bruinstroop, E., Yi, C. X., Klieverik, L., Liu, J., & Fliers, E. (2014). Hormonal control of metabolism by the hypothalamus-autonomic nervous system-liver axis. Frontiers of Hormone Research, 42, 1–28.

Karaismailoglu, S., Tuncer, M., Bayrak, S., Erdogan, G., Ergun, E. L., & Erdem, A. (2017). The perinatal effects of maternal caffeine intake on fetal and neonatal brain levels of testosterone, estradiol, and dihydrotestosterone in rats. Naunyn-Schmiedeberg’s Archives of Pharmacology, 390(8), 827–838.

Kazakov, V. N., & Natrus, L. V. (2005). Modulation of neuronal impulse activity of the anterior hypothalamus as a functional basis of the mechanisms underlying hypothalamic control. Neurophysiology, 37, 463–474.

Krivokul's'kij, O. B., & Kondras', N. M. (2014). Osnovni tendenciji spozhivannja kavi v sviti ta Ukraini: Suspilno-geografichnij aspect [Major trends of coffee consumption in the world and Ukraine: Human-geographical aspect]. Ekonomіchna ta Socіal'na Geografіja, 69, 299–307 (in Ukrainian).

Lazarus, M., Shen, H. Y., Cherasse, Y., Qu, W. M., Huang, Z. L., Bass, C. E., Winsky-Sommerer, R., Semba, K., Fredholm, B. B., Boison, D., Hayaishi, O., Urade, Y., & Chen, J. F. (2011). Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens. The Journal of Neuroscience, 31(27), 10067–10075.

Lucassen, P. J., Heine, V. M., Muller, M. B., van der Beek, E. M., Wiegant, V. M., De Kloet, E. R., Joels, M., Fuchs, E., Swaab, D. F., & Czeh, B. (2006). Stress, depression and hippocampal apoptosis. CNS and Neurological Disorders Drug Targets, 5(5), 531–546.

Majkova, T. N., Lukashjov, S. N., & Piramidov, M. A. (2004). Javlenie samoreguljacii elektrogeneza central'noj nejronal'noj predachi mozga cheloveka [The phenomenon of self-electrogenesis central neuronal predachi human brain]. Vestnik Rossijskoj Akademii Estestvenih Nauk, 4(1), 64 (in Russian).

Malyshev, J. I., & Manuhina, E. B. (1998). Stress, adaptacija i oksid azota [Stress, adaptation and nitric oxide]. Biohimija, 63(7), 992–1006 (in Russian).

McEwen, B. S. (2008). Understanding the potency of stressful early life experiences on brain and body function. Metabolism, 57(2), 11–15.

Meerson, F. Z. (1993). Adaptacionnaja medicina: Mehanizmy i zashhitnye effekty adaptacii [Adaptation medicine: Mechanisms and protective effects of adaptation]. Hypoxia Medical LTD, Moscow (in Russian).

Metodicheskie rekomendacii po klinicheskomu ispytaniju lekarstvennyh sredstv v Ukraine (1999) [Methodical recommendations for the clinical trial of medicinal products in Ukraine]. Кyiv (in Russian).

Morita, K., Sekiyama, A., & Rokutan, K. (2005). Stress and central neuroendocrine networks. No To Shinkei, 57(5), 397–406.

Nabbi-Schroeter, D., Elmenhorst, D., Oskamp, A., Laskowski, S., Bauer, A., & Kroll, T. (2018). Effects of long-term caffeine consumption on the adenosine A1 receptor in the rat brain: An in vivo pet study with [18F]CPFPX. Molecular Imaging and Biology, 20(2), 284–291.

Pacak, K., Palkovits, M., & Kvetnasky, R. (1995). Effects of various stressors on in vivo notepinephrine release in the hypothalamic paraventricular nucleus and on the pituitary-adrenocortical axis. Annals of the New York Academy of Sciences, 771, 115–130.

Paxinos, G., & Watson, C. (2013). The rat brain in stereotaxic coordinates. 7th ed. Academic Press, Imprint.

Ploshchyk, N. (2013). The world coffee sector under conditions of the second wave of the economic recession. Journal of Intercultural Management, 3(5), 91–101.

Poole, R., Kennedy, O. J., Roderick, P., Fallowfield, J. A., Hayes, P. C., & Parkes, J. (2017). Coffee consumption and health: Umbrella review of meta-analyses of multiple health outcomes. British Medical Journal, 359, j5024.

Pshennikova, M. G. (2000). Fenomen stressa [The phenomenon of stress]. Patologicheskaja Fiziologija i Eksperimental'naja Terapija, 2, 24–31 (in Russian).

Ralevic, V., & Burnstock, G. (1998). Receptors for purines and pyrimidines. Pharmacological Reviews, 50(3), 413–492.

Scher, I., Stewart, W. F., & Lipton, R. B. (2004). Caffeine as a risk factor for chronic daily headache: A population-based study. Neurology, 63(11), 2022–2027.

Sominsky, L., Jasoni, C. L., Twigg, H. R., & Spencer, S. J. (2018). Hormonal and nutritional regulation of postnatal hypothalamic development. The Journal of Endocrinology, 237(2), 47–64.

Talalaenko, A. N., Pankrat'ev, D. V., & Goncharenko, N. V. (2002). O monoaminergicheskih i aminokislotergicheskih mehanizmah zadnego gipotalamusa v realizacii antiaversivnyh effektov anksiossedativnyh i anksioselektivnyh sredstv na razlichnyh modeljah trevogi [About monoaminergic and aminoacidic mechanisms of the posterior hypothalamus in the realization of anti-inversion effects of anksiosedative and anxioselective agents in various anxiety models]. Jeksperimental’naja i Klinicheskaja Farmakologija, 65(5), 22–26 (in Russian).

Trahtenberg, I. M. (Ed.). (2001). Osnovnye pokazateli fiziologicheskoj normy u cheloveka [The main indicators of physiological norm in humans]. Avicena, Кyiv (in Russian).

Turic'ka, T. G., Lukashov, S. M., & Ljashenko, V. P. (2016). Efekty vplyvu hronіchnoji kofejinovoji alіmentacіji na pokazniky fonovoji elektrychnoji aktivnostі neokorteksu shhurіv [Effects of chronic caffeine alimentation on the performance indicators of rat neocortex background electrical activity]. Experimental Physiology and Biochemistry, 75(3), 11–16.

Vejn, A. M. (2003). Vegetativnye rasstrojstva [Autonomic dysfunction]. MIA, Moscow (in Russian).

Viani, R. (1993). The composition of coffee. In: Garatini, S. (Ed). Caffeine, coffee and health. Raven Press, New York. Pp. 17–41.

Vorob'eva, T. M., & Koljadko, S. P. (2007). Jelektricheskaja aktivnost' mozga (priroda, mehanizmy, funkcional'noe znachenie) [The electrical activity of the brain (the nature, mechanisms, functional significance)]. Eksperimental'naja i Klinicheskaja Medicina, 2, 4–11 (in Ukrainian).

Xu, D., Zhang, B., Liang, G., Ping, J., Kou, H., Li, X., Xiong, J., Hu, D., Chen, L., Magdalou, J., & Wang, H. (2012). Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes hypothalamic-pituitary-adrenal axis inhibition in fetal rats. PLoS One, 7(9), e44497.

Yadegari, M., Khazaei, M., Anvari, M., & Eskandari, M. (2016). Prenatal caffeine exposure impairs pregnancy in rats. International Journal of Fertility and Sterility, 9(4), 558–562.

Yoo, S., & Blackshaw, S. (2018). Regulation and function of neurogenesis in the adult mammalian hypothalamus. Progress in Neurobiology, in press.

Zapadnjuk, I. P., Zapadnjuk, E. A., Zaharija, E. A., & Zapadnjuk, B. V. (1983). Laboratornye zhivotnye: Razvedenie, soderzhanie, ispol'zovanie v eksperimente [Laboratory animals: Breeding, content, use in experiment]. Vishha Shkola, Kyiv (in Russian).

Zulli, A., Smith, R. M., Kubatka, P., Novak, J., Uehara, Y., Loftus, H., Qaradakhi, T., Pohanka, M., Kobyliak, N., Zagatina, A., Klimas, J., Hayes, A., La Rocca, G., Soucek, M., & Kruzliak, P. (2016). Caffeine and cardiovascular diseases: Critical review of current research. European Journal of Nutrition, 55(4), 1331–1343.

How to Cite
Turitskaya, T. G., Lukashev, S. N., Lyashenko, V. P., & Sidorenko, G. G. (2018). The features of summary background electric activity of the hypothalamus of rats under conditions of chronic caffeine alimentation. Regulatory Mechanisms in Biosystems, 9(3), 417-425.

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