Abstract
The purpose of this study was to investigate the effects of treadmill exercise training on obesity-induced behavioral changes in high-fat diet (HFD)-induced male rats. In this study, 40 male Sprague–Dawley rats were divided into 4 groups after they were weaned: Control (C), Exercise (E), Obese (O) and Obese + Exercise (O + E). For the obesity model % 60 high-fat diet were applied. After obesity was induced, rats were either moderate aerobic exercise (treadmill running) trained or left untrained. Different tasks to assess spatial learning and memory (Morris water maze test (MWMT)), depressive-like behavior (forced swimming test(FST), tail suspension test (TST) and anxiety-like behavior (light–dark test (LDT) and open field test (OFT)) were conducted. Exercise caused a significant reduction in duration of immobility in the O group in FST and the decrease in immobility in the O + E rats in TST. The O + E rats demonstrated a significant increase in the time spent in the light box as compared to the O group in the LDT. The O + E rats did not show any behavioral alterations as compared to all the other groups in the OFT. In the O + E group, there was a significant increase in the time spent in the target quadrant compared to the O group in the MWMT. Our results support that treadmill exercise could improve cognitive, depressive-like, anxiety-like behavioral changes in the HFD-induced obese rats.
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Alsio J, Roman E, Olszewski PK, Jonsson P, Fredriksson R, Levine AS, Meyerson BJ, Hulting AL, Lindblom J, Schioth HB (2009) Inverse association of high-fat diet preference and anxiety-like behavior: a putative role for urocortin 2. Genes Brain Behav 8(2):193–202. https://doi.org/10.1111/j.1601-183X.2008.00464.x
Andre C, Dinel AL, Ferreira G, Laye S, Castanon N (2014) Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation. Brain Behav Immun 41:10–21. https://doi.org/10.1016/j.bbi.2014.03.012
Armario A, Gavalda A, Marti O (1988) Forced swimming test in rats: effect of desipramine administration and the period of exposure to the test on struggling behavior, swimming, immobility and defecation rate. Eur J Pharmacol 158(3):207–212. https://doi.org/10.1016/0014-2999(88)90068-4
Aslani S, Vieira N, Marques F, Costa PS, Sousa N, Palha JA (2015) The effect of high-fat diet on rat’s mood, feeding behavior and response to stress. Transl Psychiatry 5(11):e684. https://doi.org/10.1038/tp.2015.178
Asmundson GJ, Fetzner MG, Deboer LB, Powers MB, Otto MW, Smits JA (2013) Let’s get physical: a contemporary review of the anxiolytic effects of exercise for anxiety and its disorders. Depress Anxiety 30(4):362–373. https://doi.org/10.1002/da.22043
Babyak M, Blumenthal JA, Herman S, Khatri P, Doraiswamy M, Moore K, Craighead WE, Baldewicz TT, Krishnan KR (2000) Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med 62(5):633–638
Baker DG, West SA, Nicholson WE, Ekhator NN, Kasckow JW, Hill KK, Bruce AB, Orth DN, Geracioti TD (1999) Serial CSF corticotropin-releasing hormone levels and adrenocortical activity in combat veterans with posttraumatic stress disorder. Am J Psychiatry 156(4):585–588. https://doi.org/10.1176/ajp.156.4.585
Bakshi VP, Kalin NH (2000) Corticotropin-releasing hormone and animal models of anxiety: gene–environment interactions. Biol Psychiat 48(12):1175–1198
Bocarsly ME, Fasolino M, Kane GA, LaMarca EA, Kirschen GW, Karatsoreos IN, McEwen BS, Gould E (2015) Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function. Proc Natl Acad Sci U S A 112(51):15731–15736. https://doi.org/10.1073/pnas.1511593112
Buchenauer T, Behrendt P, Bode F, Horn R, Brabant G, Stephan M, Nave H (2009) Diet-induced obesity alters behavior as well as serum levels of corticosterone in F344 rats. Physiol Behav 98(5):563–569
Bugg JM, Shah K, Villareal DT, Head D (2012) Cognitive and neural correlates of aerobic fitness in obese older adults. Exp Aging Res 38(2):131–145. https://doi.org/10.1080/0361073X.2012.659995
Canpolat S, Ulker N, Yardimci A, Bulmus O, Ozdemir G, Sahin Z, Ercan Z, Serhatlioglu I, Kacar E, Ozcan M, Turk G, Ozkan Y, Atmaca M, Yilmaz B, Kelestimur H (2016) Studies on the reproductive effects of chronic treatment with agomelatine in the rat. Eur J Pharmacol 770:33–39. https://doi.org/10.1016/j.ejphar.2015.11.054
Chaouloff F, Durand M, Mormede P (1997) Anxiety- and activity-related effects of diazepam and chlordiazepoxide in the rat light/dark and dark/light tests. Behav Brain Res 85(1):27–35. https://doi.org/10.1016/s0166-4328(96)00160-x
Chermat R, Thierry B, Mico JA, Steru L, Simon P (1986) Adaptation of the tail suspension test to the rat. J Pharmacol 17(3): 348–350. http://www.ncbi.nlm.nih.gov/pubmed/3795979
Crawley JN (1981) Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines. Pharmacol Biochem Behav 15(5):695–699. https://doi.org/10.1016/0091-3057(81)90007-1
Crawley JN (1985) Exploratory behavior models of anxiety in mice. Neurosci Biobehav Rev 9(1):37–44. https://doi.org/10.1016/0149-7634(85)90030-2
Crawley J, Goodwin FK (1980) Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol Biochem Behav 13:167–170. https://doi.org/10.1016/0091-3057(80)90067-2
Cryan JF, Page ME, Lucki I (2005) Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment. Psychopharmacology 182:335–344
da Costa ED, da Silva WA, Guimarães AT, de Oliveira MB, da Silva Castro AL, da Silva Torres IL, Malafaia G (2015) Predictive behaviors for anxiety and depression in female Wistar rats subjected to cafeteria diet and stress. Physiol Behav 1:252–263. https://doi.org/10.1016/j.physbeh.2015.07.016
Danielsson L, Papoulias I, Petersson E-L, Carlsson J, Waern M (2014) Exercise or basic body awareness therapy as add-on treatment for major depression: a controlled study. J Affect Disord 168:98–106
Dao AT, Zagaar MA, Alkadhi KA (2015) Moderate treadmill exercise protects synaptic plasticity of the dentate gyrus and related signaling cascade in a rat model of Alzheimer’s disease. Mol Neurobiol 52(3):1067–1076
de Noronha SR, Campos GV, Abreu AR, de Souza AA, Chianca DA Jr, de Menezes RC (2017) High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats. Behav Brain Res 316:38–46
Detke MJ, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants. Psychopharmacology 121(1):66–72. https://doi.org/10.1007/BF02245592
Dimeo F, Bauer M, Varahram I, Proest G, Halter U (2001) Benefits from aerobic exercise in patients with major depression: a pilot study. Br J Sports Med 35(2):114–117. https://doi.org/10.1136/bjsm.35.2.114
Dong C, Sanchez LE, Price RA (2004) Relationship of obesity to depression: a family-based study. Int J Obes Relat Metab Disord 28(6):790–795. https://doi.org/10.1038/sj.ijo.0802626
Dunn AL, Trivedi MH, Kampert JB, Clark CG, Chambliss HO (2005) Exercise treatment for depression: efficacy and dose response. Am J Prev Med 28(1):1–8. https://doi.org/10.1016/j.amepre.2004.09.003
Eudave DM, BeLow MN, Flandreau EI (2018) Effects of high fat or high sucrose diet on behavioral-response to social defeat stress in mice. Neurobiol Stress 9:1–8. https://doi.org/10.1016/j.ynstr.2018.05.005
Fagundo AB, de la Torre R, Jimenez-Murcia S, Aguera Z, Granero R, Tarrega S, Botella C, Banos R, Fernandez-Real JM, Rodriguez R, Forcano L, Fruhbeck G, Gomez-Ambrosi J, Tinahones FJ, Fernandez-Garcia JC, Casanueva FF, Fernandez-Aranda F (2012) Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity. PLoS ONE 7(8):e43382. https://doi.org/10.1371/journal.pone.0043382
Faith MS, Matz PE, Jorge MA (2002) Obesity–depression associations in the population. J Psychosom Res 53(4):935–942
Farhangi MA, Nameni G, Hajiluian G, Mesgari-Abbasi M (2017) Cardiac tissue oxidative stress and inflammation after vitamin D administrations in high fat- diet induced obese rats. BMC Cardiovasc Disord 17(1):161. https://doi.org/10.1186/s12872-017-0597-z
Fedotova JO, Hartmann G, Lenard L, Sapronov NS (2004) Involvement of 5-HT1A receptors in passive avoidance learning in intact and ovariectomized female rats. Acta Physiol Hung 91:185–196. https://doi.org/10.1556/APhysiol.91.2004.3-4.2
Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu YY, Bahalim AN, Farzadfar F, Riley LM, Ezzati M (2011) Global burden of metabolic risk factors of chronic diseases collaborating group (body mass index). National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet 377:557–567. https://doi.org/10.1016/s0140-6736(10)62037-5
Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, Montori VM (2007) Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 49(4):403–414
Greist JH, Klein MH, Eischens RR, Faris J, Gurman AS, Morgan WP (1979) Running as treatment for depression. Compr Psychiatry 20(1):41–54
Hariri N, Thibault L (2010) High-fat diet-induced obesity in animal models. Nutr Res Rev 23(2):270–299. https://doi.org/10.1017/S0954422410000168
Hashemi Nosrat Abadi T, Vaghef L, Babri S, Mahmood-Alilo M, Beirami M (2013) Effects of different exercise protocols on ethanol induced spatial memory impairment in adult male rats. Alcohol 47:309–316. https://doi.org/10.1016/j.alcohol.2013.01.008
Horowitz JF, Klein S (2000) Lipid metabolism during endurance exercise. Am J Clin Nutr 72(2 Suppl):558S-563S. https://doi.org/10.1093/ajcn/72.2.558S
Hryhorczuk C, Sharma S, Fulton SE (2013) Metabolic disturbances connecting obesity and depression. Front Neurosci 7:1–14. https://doi.org/10.3389/fnins.2013.00177
Huang W, Liu R, Ou Y, Li X, Qiang O, Yu T, Tang CW (2013) Octreotide promotes weight loss via suppression of intestinal MTP and apoB48 expression in diet-induced obesity rats. Nutrition 29(10):1259–1265. https://doi.org/10.1016/j.nut.2013.01.013
Jaric I, Rocks D, Cham H, Herchek A, Kundakovic M (2019) Sex and estrous cycle effects on anxiety- and depression-related phenotypes in a two-hit developmental stress model. Front Mol Neurosci 12:74. https://doi.org/10.3389/fnmol.2019.00074
Jauch-Chara K, Oltmanns KM (2014) Obesity – a neuropsychological disease? Systematic review and neuropsychological model. Prog Neurobiol 114:84–101
Kang SS, Jeraldo PR, Kurti A, Miller ME, Cook MD, Whitlock K, Goldenfeld N, Woods JA, White BA, Chia N, Fryer JD (2014) Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition. Mol Neurodegener 9:36. https://doi.org/10.1186/1750-1326-9-36
Kelestimur H, Bulmus O, Serhatlioglu I, Ercan Z, Kaya SO, Yardimci A, Ulker N, Kacar E, Canpolat S (2021) Effects of treadmill exercise on sexual behavior and reproductive parameters in chronically stressed-male rats. Physiol Res 70(5):765–775. https://doi.org/10.33549/physiolres.934585
Kim BS, Kim MY, Leem YH (2011) Hippocampal neuronal death induced by kainic acid and restraint stress is suppressed by exercise. Neuroscience 194:291–301. https://doi.org/10.1016/j.neuroscience.2011.06.029
Kloiber S, Ising M, Reppermund S, Horstmann S, Dose T, Majer M, Zihl J, Pfister H, Unschuld PG, Holsboer F, Lucae S (2007) Overweight and obesity affect treatment response in major depression. Biol Psychiatry 62(4):321–326. https://doi.org/10.1016/j.biopsych.2006.10.001
Lee MO (1929) Determination of the surface area of the white rat with its application to the expression of metabolic results. Am J Physiol 89:24–33
Luppino FS, de Wit LM, Bouvy PF, Stijnen T, Cuijpers P, Penninx BW, Zitman FG (2010) Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 67(3):220–229. https://doi.org/10.1001/archgenpsychiatry.2010.2
Merlo Pich E, Samanin R (1989) A two-compartment exploratory model to study anxiolytic/anxiogenic effects of drugs in the rat. Pharmacol Res 21(5):595–602. https://doi.org/10.1016/1043-6618(89)90201-6
Moraska A, Deak T, Spencer RL, Roth D, Fleshner M (2000) Treadmill running produces both positive and negative physiological adaptations in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol 279:R1321-1329
Mueller K, Sacher J, Arelin K, Holiga S, Kratzsch J, Villringer A, Schroeter ML (2012) Overweight and obesity are associated with neuronal injury in the human cerebellum and hippocampus in young adults: a combined MRI, serum marker and gene expression study. Transl Psychiatry 2:e200. https://doi.org/10.1038/tp.2012.121
Murphy M, Mercer JG (2013) Diet-regulated anxiety. Int J Endocrinol 2013:701967. https://doi.org/10.1155/2013/701967
Patki G, Li L, Allam F, Solanki N, Dao AT, Alkadhi K, Salim S (2014) Moderate treadmill exercise rescues anxiety and depression-like behavior as well as memory impairment in a rat model of posttraumatic stress disorder. Physiol Behav 10:47–53
Ploughman M, Granter-Button S, Chernenko G, Attwood Z, Tucker BA, Mearow KM, Corbett D (2007) Exercise intensity influences the temporal profile of growth factors involved in neuronal plasticity following focal ischemia. Brain Res 1150(207):216. https://doi.org/10.1016/j.brainres.2007.02.065
Porsolt RD, LePichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266:730–732
Prasad A, Prasad C (1996) Short-term consumption of a diet rich in fat decreases anxiety response in adult male rats. Physiol Behav 60(3):1039–1042
Radovic S, Gordon MS, Melvin GA (2017) Should we recommend exercise to adolescents with depressive symptoms? A meta-analysis. J Paediatr Child Health 53:214–220
Ríos-Kristjánsson JG, Rizo-Roca D, Kristjánsdóttir KM, Núñez-Espinosa CA, Torrella JR, Pages T, Viscor G (2019) A three-criteria performance score for rats exercising on a running treadmill. PLoS ONE 14(7):e0219167. https://doi.org/10.1371/journal.pone.0219167
Roberts RE, Deleger S, Strawbridge WJ, Kaplan GA (2003) Prospective association between obesity and depression: evidence from the Alameda County study. Int J Obes 27(4):514–521
Salmon P (2001) Effects of physical exercise on anxiety, depression, and sensitivity to stress: a unifying theory. Clin Psychol Rev 21:33–61. https://doi.org/10.1016/s0272-7358(99)00032-x
Sivanathan S, Thavartnam K, Arif S, Elegino T, McGowan PO (2015) Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats. Behav Brain Res 286:265–270. https://doi.org/10.1016/j.bbr.2015.02.036
Solleiro DR, Guasti AF (2018) Influence of sex and estrous cycle on blood glucose levels, body weight gain, and depressive-like behavior in streptozotocin-induced diabetic rats. Physiol Behav 194:560–567. https://doi.org/10.1016/j.physbeh.2018.06.033
Stanton R, Reaburn P (2014) Exercise and the treatment of depression: a review of the exercise program variables. J Sci Med Sport 17(2):177–182
Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology 85:367–370. https://doi.org/10.1007/BF00428203
Svensson M, Rosvall P, Boza-Serrano A, Andersson E, Lexell J, Deierborg T (2016) Forced treadmill exercise can induce stress and increase neuronal damage in a mouse model of global cerebral ischemia. Neurobiol Stress 5:8–18
Uysal N, Kiray M, Sisman A, Camsari U, Gencoglu C, Baykara B, Cetinkaya C, Aksu I (2015) Effects of voluntary and involuntary exercise on cognitive functions, and VEGF and BDNF levels in adolescent rats. Biotech Histochem 90(1):55–68
Vogel HG (2002) Drug discovery and evaluation: pharmacological assays. Springer, New York
Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1:848–858. https://doi.org/10.1038/nprot.2006.116
Walsh RN, Cummins RA (1976) The Open-Field Test: a critical review. Psychol Bull 83(3): 482–504. http://www.ncbi.nlm.nih.gov/pubmed/17582919
Xu L, Xu S, Lin L, Gu X, Fu C, Fang Y, Li X, Wang X (2018) High-fat diet mediates anxiolytic-like behaviors in a time-dependent manner through the regulation of SIRT1 in the brain. Neuroscience 3721:237–245
Yamada N, Katsuura G, Ochi Y, Ebihara K, Kusakabe T, Hosoda K, Nakao K (2011) Impaired CNS leptin action is implicated in depression associated with obesity. Endocrinology 152(7):2634–2643
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This work was supported by TUBITAK ≠ 114S179.
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H.K. conceived and designed the project. I.S. contributed to evaluation and analysis of data; Z.E. O.B. A.Y. and E.K. performed all animal experiments; H.K. and Z.E. wrote the manuscript through contributions of all the authors. All authors reviewed the content and approved the final version of the manuscript.
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Bulmus, O., Ercan, Z., Kacar, E. et al. Treadmill exercise training improves the high-fat diet-induced behavioral changes in the male rats. BIOLOGIA FUTURA 73, 483–493 (2022). https://doi.org/10.1007/s42977-022-00144-1
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DOI: https://doi.org/10.1007/s42977-022-00144-1