The Effects of Physical Exercise on Spatial Learning and Serotonin Levels in the Brain of Adult Rats

Annisa Rahmah Furqaani, Sri Redjeki, Dwirini Retno Gunarti


Physical exercise can enhance tryptophan transport into the brain so that it will also increase serotonin levels in the brain. Therefore, it may influence many brain functions, such as learning and memory. This study aimed to determine the effect of physical exercise on spatial learning and serotonin levels in the brain of adult male Wistar rats. Biochemistry Laboratory of Department of Biochemistry & Molecular Biology, Faculty of Medicine, Universitas Indonesia was the study place which conducted in January–April 2013. Sixteen adult male rats randomly divided into two groups, the control group, and the treatment group. Physical exercise for the treatment group for four weeks using the animal treadmill at 15 m/min in speed for 15 minutes in the 1st week and 25 minutes for the next three weeks. Learning and memory test using water-E maze apparatus once a week. At the end of the exercised period, animals were sacrificed, and the brains were isolated. The measurement of serotonin and tryptophan levels was done using high-performance liquid chromatography (HPLC). The results showed that physical exercise improved animals performance in learning and memory test, exercised group made fewer errors at third and fourth week (p<0.05). Serotonin levels in the brain of exercised group was significantly higher than that in control group (p<0.05). These results indicated that the enhancement of serotonin levels in the brain induced by physical exercise is involved in improving spatial learning and memory.



Latihan fisik diketahui dapat meningkatkan transpor triptofan melewati sawar otak sehingga dapat meningkatkan kadar serotonin di otak. Oleh karena itu, latihan fisik berperan memengaruhi berbagai fungsi otak termasuk proses belajar dan memori. Penelitian ini bertujuan mengetahui pengaruh latihan fisik aerobik dengan intensitas yang ringan terhadap kemampuan belajar spasial serta kadar serotonin pada otak tikus Wistar dewasa. Penelitian ini dilakukan di Laboratorium Biokimia, Departemen Biokimia & Biologi Molekuler, Fakultas Kedokteran, Universitas Indonesia, Jakarta periode Januari–April 2013. Enam belas ekor tikus jantan dewasa dibagi secara acak menjadi dua kelompok, yaitu kelompok kontrol dan kelompok perlakuan. Latihan fisik diberikan kepada kelompok perlakuan selama 4 minggu menggunakan animal treadmill dengan kecepatan 15 m/menit selama 15 menit pada minggu pertama dan 25 menit pada 3 minggu berikutnya. Uji belajar dan memori dengan perangkat water-E maze dilakukan satu kali/minggu. Setelah masa latihan fisik selesai, hewan coba dikorbankan dan jaringan otak diisolasi. Pengukuran kadar serotonin dan triptofan pada otak dilakukan menggunakan kromatografi cair kinerja tinggi (KCKT). Hasil penelitian menunjukkan bahwa jumlah kesalahan yang dilakukan oleh kelompok perlakuan lebih sedikit secara signifikan pada uji belajar dan memori ke-3 dan ke-4 (p<0,05). Kadar serotonin lebih tinggi secara signifikan pada otak kelompok perlakuan (p<0,05). Hasil penelitian ini mengindikasikan bahwa peningkatan kadar serotonin pada otak yang diinduksi oleh latihan fisik aerobik intensitas ringan terlibat dalam meningkatkan kemampuan belajar dan memori spasial.


Belajar dan memori; brain; latihan fisik; learning and memory; otak; physical exercise; serotonin

Full Text:



Tanzila RA, Bustan MF. Pengaruh latihan interval intensitas tinggi terhadap denyut nadi mahasiswa kedokteran. GMHC. 2017;5(1):47–50.

Tresnasari C, Basuki A, Defi IR. Efektivitas latihan penguatan terhadap kemampuan fungsional anggota gerak atas pada pasien strok iskemi fase subakut. GMHC. 2017;5(3): 182–8.

McAuley E, Kramer AF, Colcombe SJ. Cardiovascular fitness and neurocognitive function in older adults: a brief review. Brain Behav Immun. 2004;18(3):214–20.

Ahmadiasl N, Alaei H, Hänninen O. Effect of exercise on learning, memory, and levels of epinephrine in rat’s hippocampus. J Sport Sci Med. 2003;2(3):106–9.

Hertzog C, Kramer AF, Wilson RS, Lindenberger U. Enrichment effects on adult cognitive development, can the functional capacity of older adults be preserved and enhanced? Psychol Sci Public Interest. 2009;9(1):1–65.

van Praag H, Christie BR, Sejnowski TJ, Gage FH. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999;96(23):13427–31.

Parle M, Vasudevan M, Singh N. Swim everyday to keep dementia away. J Sport Sci Med. 2005;4(1):37–46.

Van der Borght K, Havekes R, Bos T, Eggen BJL, Van der Zee EA. Exercise improves memory acquisition and retrieval in the y-maze task: relationship with hippocampal neurogenesis. Behav Neurosci. 2007;121(2):324–34.

Naylor AS, Bull C, Nilsson MKL, Zhu C, Björk-Eriksson T, Eriksson PS, et al. Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc Natl Acad Sci U S A. 2008;105(38):14632–7.

Ayoub RS. Effect of exercise on spatial learning and memory in male diabetic rats. Int J Diabetes Metab. 2009;17:93–8.

Rhodes SJ, Gammie CS, Garland JrT. Neurobiology of mice selected for high voluntary wheel-running activity. Integr Comp Biol. 2005;45(3):438–55.

Kramer AF, Erickson KI, Colcombe SJ. Exercise, cognition, and the aging brain. J Appl Physiol. 2006;1014):1237–42.

Antunes HKM, Santos RF, Cassilhas R, Santos RVT, Bueno OFA, de Mello MT. Reviewing on physical exercise and cognitive function. Rev Bras Med Esporte. 2006;12(2):97e–103.

Meeusen R, De Meirleir K. Exercise and brain neurotransmission. Sports Med. 1995;20(3):160–88.

Farris JW, Hinchcliff KW, McKeever KH, Lamb DR, Thompson DL. Effect of tryptophan and of glucose on exercise capacity of horses. J Appl Physiol. 1998;85(3):807–16.

Smriga M, Kameishi M, Torii K. Exercise-dependent preferences for a mixture of branched-chain amino acid and homeostatic control of brain serotonin in exercising rats. J Nutr. 2006;136(2):548S–52.

Chaouloff F, Elghozi JL, Guezennec Y, Laude D. Effect of conditioned running on plasma, liver, and brain tryptophan, and on brain 5-hydroxytryptamine of the rat. Br J Pharmacol. 1985;86(1):33–41.

Grimmett A, Sillence MN. Calmatives for the excitable horse: a review of L-tryptophan. Vet J. 2005;170(1):24–32.

Kema IP, de Vries EGE, Muskiet FAJ. Review clinical chemistry of serotonin and metabolites. J Chromatogr B Biomed Sci Appl. 2000;747(1–2):33–48.

Green AR. Neuropharmacology of 5-hydroxytryptamine. Br J Pharmacol. 2006;147(Suppl 1):S145–52.

Harrell AV, Andrea AM. Improvements in hippocampal-dependent learning and decremental attention in 5-HT3 receptor overexpressing mice. Learn Mem. 2003;10(5):410–9.

Harvey JA. Role of the serotonin 5-HT2A receptor in learning. Learn Mem. 2003;10:355–62.

Djavadian RL. Serotonin and neurogenesis in the hippocampal dentate gyrus of adult mammals. Acta Neurobiol Exp. 2004;64(2):189–200.

Wesolowska A. In the search for selective ligands of 5-HT5, 5-HT6, 5-HT7 serotonin receptors. Pol J Pharmacol. 2002;54(4):327–41.

Barthet G, Framery B, Gaven F, Pellisier L, Reiter E, Claeysen S, et al. 5-hydroxytryptamine 4 receptor activation of the extracellular signal-regulated kinase pathway depends on Src but not on G protein or β-arrestin signaling. Mol Biol Cell. 2007;18(16):1979–91.

Konkel A, Cohen NJ. Relational memory and the hippocampus: representations and methods. Front Neurosci. 2009;3(2):166–74.

Albek DS, Sano K, Prewitt GE, Dalton L. Mild forced treadmill exercise enhances spatial learning in the aged rat. Behav Brain Res. 2006;168(2):345–8.

Liu YF, Chen HI, Wu CL, Kuo YM, Yu L, Huang AM, et al. Different effects of treadmill running and wheel running on spatial or aversive learning and memory: roles of amygdalar brain-derived neurotrophic factor and synaptotagmin 1. J Physiol. 2009;587(13):3221–31.

Kobilo T, Liu QR, Gandhi K, Mughal M, Shaham Y, van Praag H. Running is the neurogenic and neurotrophic stimulus in environmental enrichment. Learn Mem. 2011;18(9):605–9.

Ke Z, Yip SP, Li L, Zheng XX, Tong KY. The effects of voluntary, involuntary, and forced exercise on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model. PloS One. 2011;6(2):e16643.

Fukushima T, Ohtbsubo T, Tsuda M, Yanagawa Y, Hori Y. Facilitatory actions of serotonin type 3 receptors on GABAergic inhibitory synaptic transmission in the superficial dorsal horn. J Neurophysiol. 2009;102(3):1459–71.

King MV, Marsden CA, Fone KC. A role for the 5-HT1A, 5-HT4 and 5-HT6 receptors in learning memory. Trends Pharmacol Sci. 2008;29(9):482–92.

van Praag H, Shubert T, Zhao C, Gage FH. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci. 2005;25(38):8680–5.

Swain RA, Harris AB, Wiener EC, Dutka MV, Morris HD, Theien BE, et al. Prolonged exercise induces angiogenesis and increases cerebral blood volume in primary motor cortex of the rat. Neuroscience. 2003;117(4):1037–46.

Lopez-Lopez C, LeRoith D, Torres-Aleman I. Insulin-like growth factor I is required for vessel remodeling in the adult brain. Proc Natl Acad Sci U S A. 2004;101(26):9833–8.

Fabel K, Fabel K, Tam B, Kaufer D, Baiker A, Simmons N, et al. VEGF is necessary for exercise-induced adult hippocampal neurogenesis. Eur J Neurosci. 2003;18(10):2803–12.

Ogren SO, Eriksson TM, Elvander-Tottie E, D`Addario C, Ekström JC, Svenningsson P, et al. The role of 5-HT1A receptors in learning and memory. Behav Brain Res. 2008;195(1):54–77.

Mitchell ES, Neumaier JF. 5-HT6 receptors: a novel target for cognitive enhancement. Pharmacol Ther. 2005;108(3):320–3.



  • There are currently no refbacks.

pISSN 2301-9123 | eISSN 2460-5441

Visitor since 19 October 2016:

View My Stats

Free counters!

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.