The Effect of Forced Exercise on Striatal and Serum Serotonin Levels in a Parkinson’s Mouse Model

Abstract views: 327 / PDF downloads: 201




forced exercise, serotonin, treadmill exercise, Parkinson's disease, dopamine


Objective: The general treatment approach for Parkinson's disease (PD) is L-dopa administration. While L-dopa only relieves dopaminergic deficiency, it has no effect on the serotonergic system, which is thought to be impaired in the disease. The limitations of current treatment methods have made it necessary to discover new approaches to the treatment of the disease. Studies conducted in recent years report that different types of exercises applied lead to improvement in the symptoms of PD. Exercising decreases serotonin levels and increases dopamine levels. However, the effect of exercise on serotonin levels together with dopamine in PD and its effect on non-motor symptoms such as anxiety and depression are unknown.

Methods: PD is created using MPTP. The exercise groups were given challenging treadmill exercises for 6 weeks. Serotonin and dopamine levels were measured in the striatum and serum. Parkinson's symptoms were examined with pole test and behavioral tests.

Results: Exercise significantly reduced bradykinesia, increased motor activity, and decreased anxiety behaviors in the exercise groups. While exercise increased striatal dopamine levels in all exercise groups, there was no difference in striatal serotonin levels. However, the serotonin serum level was decreased in the PD model group. While treadmill exercise increased striatal dopamine levels in the Parkinson's mouse model, it did not cause any change in striatal serotonin levels. However, the decrease in serum serotonin level was determined only in the MPTP group.

Conclusion: The fact that the decrease in serotonin level was only in the disease group and the lower level of anxiety observed in behavioral experiments suggested that regular treadmill exercise was the reason. However, this improvement was not observed in cases where the anxiety level was very high.


Metrics Loading ...


Damier P, Hirsch EC, Agid Y, & Graybiel AM (1999) The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson’s disease. Brain: a journal of neurology. 122 (Pt 8), 1437–1448.

Ibraheem A, Ogeleyinbo I, Emmanuel K, Idar E, Oyewale J, Kunlere O, Olabiyi A.A., Adeniyi P.A (2019) Assessment of the Impacts of Selenocysteine on the Dopaminergic System in the Substantia Nigra and Striatum of 6-OHDA Parkinson’s Disease Rat Model. IBRO Reports. 7:25.

Ito H (2015) Symptoms and signs of Parkinson’s disease and other movement disorders. Deep Brain Stimulation for Neurological Disorders: Theoretical Background and Clinical Application. 21-37. ISBN: 978-3-319-08476-3

Gorton LM, Vuckovic MG, Vertelkina N, Petzinger GM, Jakowec MW, & Wood RI (2010) Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse. Behavioural brain research. 213(2):253–262.

Walsh,K, & Bennett G (2001) Parkinson’s disease and anxiety. Postgraduate medical journal. 77(904), 89–93.

Schuurman AG, van den Akker M, Ensinck KT, Metsemakers JF, Knottnerus JA, Leentjens AF, & Buntinx, F (2002) Increased risk of Parkinson’s disease after depression: a retrospective cohort study. Neurology. 58(10):1501–1504.

Chaudhuri KR, Healy DG, Schapira AH & National Institute for Clinical Excellence (2006) Non-motor symptoms of Parkinson’s disease: diagnosis and management. The Lancet. 5(3):235–245.

Laux G. (2022) Parkinson and depression: review and outlook. Journal of neural transmission. 129(5-6):601–608.

Frouni I, Kwan C, Belliveau S, Huot P (2022) Cognition and serotonin in Parkinson’s disease. Progress in brain research. 269(1):373–403.

Pedersen BK, Saltin B. (2006) Evidence for prescribing exercise as therapy in chronic disease. Scandinavian journal of medicine & science in sports. 16(Suppl 1):3–63.

Pietrelli A, Lopez-Costa J, Goñi R, Brusco A, Basso N (2012) Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats. Neuroscience. 202:252–266.

Jackson-Lewis V, Przedborski S (2007) Protocol for the MPTP mouse model of Parkinson’s disease. Nature protocols. 2(1):141–151.

Duty S, Jenner P (2011) Animal models of Parkinson’s disease: a source of novel treatments and clues to the cause of the disease. British journal of pharmacology. 164(4):1357–1391.

Tuon T, Valvassori SS, Lopes-Borges J, Luciano T, Trom CB, Silva LA, Quevedo J, Souza CT, Lira FS, Pinh, RA (2012) Physical training exerts neuroprotective effects in the regulation of neurochemical factors in an animal model of Parkinson’s disease. Neuroscience. 227:305–312.

Lau YS, Patki G, Das-Panja K, Le WD, Ahmad SO (2011) Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration. The European journal of neuroscience. 33(7):1264–1274.

Kobayashi T, Araki T, Itoyama Y, Takeshita M, Ohta T, Oshima Y (1997) Effects of L-dopa and bromocriptine on haloperidol-induced motor deficits in mice. Life sciences. 61(26):2529–2538.

Ogawa N, Mizukawa K, Hirose Y, Kajita S, Ohara S, Watanabe Y (1987) MPTP-induced parkinsonian model in mice: biochemistry, pharmacology and behavior. European neurology. 26(Suppl 1):16–23.

Kayir H, Uzbay IT (2004) Evidence for the role of nitric oxide in caffeine-induced locomotor activity in mice. Psychopharmacology. 172(1):11–15.

Rozas G, Guerra MJ, Labandeira-García JL (1997) An automated rotarod method for quantitative drug-free evaluation of overall motor deficits in rat models of parkinsonism. Brain research. Brain research protocols. 2(1):75–84.

Rozas G, López-Martín E, Guerra MJ, Labandeira-García JL (1998) The overall rod performance test in the MPTP-treated-mouse model of Parkinsonism. Journal of neuroscience methods. 83(2):165–175.

Simon DK, Tanner CM, Brundin P (2020) Parkinson Disease Epidemiology, Pathology, Genetics, and Pathophysiology. Clinics in geriatric medicine. 36(1):1–12.

Doğru NÖ, Bal R (2019) Effects of Voluntary and forced exercise on anxiety-related behaviours and motor activity in Parkinson mouse model. Eur J Ther. 25(2):97-103.

Dunn AL, Reigle TG, Youngstedt SD, Armstrong RB, Dishman RK (1996) Brain norepinephrine and metabolites after treadmill training and wheel running in rats. Medicine and science in sports and exercise. 28(2): 204–209.

Carek PJ, Laibstain SE, Carek SM (2011) Exercise for the treatment of depression and anxiety. International journal of psychiatry in medicine. 41(1):15–28.

Ozbeyli D, Gokalp AG, Koral T, Ocal OY, Dogan B, Akakin D, Yuksel M, Kasimay O (2015) Protective effect of exercise and sildenafil on acute stress and cognitive function. Physiology & behavior. 151:230–237.

Motaghinejad M, Fatima S, Karimian M, Ganji S (2016) Protective effects of forced exercise against nicotine-induced anxiety, depression and cognition impairment in rat. Journal of basic and clinical physiology and pharmacology. 27(1):19–27.

Burghardt PR, Fulk LJ, Hand GA, Wilson MA (2004) The effects of chronic treadmill and wheel running on behavior in rats. Brain research. 1019(1-2):84–96.

Taylor TN, Greene JG, Miller GW (2010) Behavioral phenotyping of mouse models of Parkinson’s disease. Behavioural brain research. 211(1):1–10.

Johnson RA (2016) Voluntary Running-Wheel Activity, Arterial Blood Gases, and Thermal Antinociception in Rats after 3 Buprenorphine Formulations. J Am Assoc Lab Anim Sci. 55(3):306–311.PMCID: 27177564

Erdogan F, Kucuk A, Gölgeli A, Liman N, Sagsoz H (2007) Assesment of The Effect of Pentylenetetrazole-induced Kindling on Behavior and Emotional Learning in Rats. EPILEPSI. 13(2):66-72.

Sasaki H, Hattori Y, Ikeda Y, Kamagata M, Iwami S, Yasuda S, Tahara Y, Shibata S (2016) Forced rather than voluntary exercise entrains peripheral clocks via a corticosterone/noradrenaline increase in PER2:LUC mice. Scientific reports. 6:27607.

Meeusen, R., & De Meirleir, K. (1995). Exercise and brain neurotransmission. Sports medicine (Auckland, N.Z.), 20(3), 160–188.

Tang C, Liu M, Zhou Z, Li H, Yang C, Yang L, Xiang J (2023) Treadmill Exercise Alleviates Cognition Disorder by Activating the FNDC5: Dual Role of Integrin αV/β5 in Parkinson’s Disease. International journal of molecular sciences. 24(9):7830.

Chaouloff F, Laude D, Merino D, Serrurrier B, Guezennec Y, Elghozi JL (1987) Amphetamine and alpha-methyl-p-tyrosine affect the exercise-induced imbalance between the availability of tryptophan and synthesis of serotonin in the brain of the rat. Neuropharmacology. 26(8):1099–1106.

Lukaszyk A, Buczko W, Wiśniewski K (1983) The effect of strenuous exercise on the reactivity of the central dopaminergic system in the rat. Polish journal of pharmacology and pharmacy. 35(1):29–36. PMID: 6684280

Bailey SP, Davis JM, Ahlborn EN (1993) Neuroendocrine and substrate responses to altered brain 5-HT activity during prolonged exercise to fatigue. Journal of applied physiology. 74(6):3006–3012.

Chaouloff F, Laude D, Elghozi JL (1989) PHysical exercise: evidence for differential consequences of tryptophan on 5-HT synthesis and metabolism in central serotonergic cell bodies and terminals. Journal of neural transmission. 78(2):121–130.

Hellhammer DH, Hingtgen JN, Wade SE, Shea PA, Aprison MH (1983) Serotonergic changes in specific areas of rat brain associated with activity--stress gastric lesions. Psychosomatic medicine. 45(2):115–122.

Cicardo VH, Carbone SE, de Rondina DC, Mastronardi IO (1986) Stress by forced swimming in the rat: effects of mianserin and moclobemide on GABAergic-monoaminergic systems in the brain. Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology. 83(1):133–135.

Acworth I, Nicholass J, Morgan B, Newsholme EA (1986) Effect of sustained exercise on concentrations of plasma aromatic and branched-chain amino acids and brain amines. Biochemical and biophysical research communications. 137(1):149–153.

Kaplan DS, Bozkurt M (2018) Investigating the most commonly applied lactate recovery method according to the positions in football. Eur J Ther. 24(4):224-229.




How to Cite

Ozkul Dogru, N., Yigit, H. K., Yildirim, A. B., Ulusal, H., Orkmez, M., Yigit, E., & Celik, H. (2023). The Effect of Forced Exercise on Striatal and Serum Serotonin Levels in a Parkinson’s Mouse Model. European Journal of Therapeutics, 29(2), 179–187.



Original Articles