Preventive Effect of Maternal Forced Exercise on Offspring Pain Perception and Intensity: The Role of 5-HT2 and D2 Receptors

Document Type : Original Article

Authors

Department of Pharmacology, School of Medicine and Razi Institute for Drug Research, Iran University of Medical Sciences, Tehran, Iran

Abstract

Background: Many previous studies showed that maternal forced exercise can reduce some central disorders in offsprings, but its clear mechanism remains unclear. In this study, the role of 5-HT2 and D2 receptors in neuroprotective effects of maternal forced exercise in offspring neurodevelopment and effect on some behaviors were evaluated. Materials and Methods: Forty-eight pregnant rats were trained by forced exercise, and some behavioral assays in their offspring were performed in the presence and absence of 5-HT2 and D2 receptor antagonists in various experimental groups. Results: Our data showed that maternal forced exercise caused increase in latency of pain perception in offsprings in hot plate test, writhing test (WT), and tail flick test. Furthermore, a decrease in intensity was shown by WT. On the other hand, treatment of mothers by forced exercise in combination with 5-HT2 and D2 receptor antagonists could inhibit these effects of forced exercise and cause disturbances in pain perception and intensity. Conclusion: Our data suggested that maternal forced exercise causes protective effects on offspring pain perception and intensity, and in this effect, 5-HT2 and D2 receptors are probably involved.

Keywords

1.
Salmon P. Effects of physical exercise on anxiety, depression, and sensitivity to stress: A unifying theory. Clin Psychol Rev 2001;21:33-61.  Back to cited text no. 1
[PUBMED]    
2.
Motaghinejad M, Motevalian M, Asadi-Ghalehni M, Motaghinejad O. Attenuation of morphine withdrawal signs, blood cortisol and glucose level with forced exercise in comparison with clonidine. Adv Biomed Res 2014;3:171.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Lawlor DA, Hopker SW. The effectiveness of exercise as an intervention in the management of depression: Systematic review and meta-regression analysis of randomised controlled trials. BMJ 2001;322:763-7.  Back to cited text no. 3
[PUBMED]    
4.
Tomporowski PD. Effects of acute bouts of exercise on cognition. Acta Psychol (Amst) 2003;112:297-324.  Back to cited text no. 4
[PUBMED]    
5.
Kramer AF, Erickson KI, Colcombe SJ. Exercise, cognition, and the aging brain. J Appl Physiol 2006;101:1237-42.  Back to cited text no. 5
[PUBMED]    
6.
Cotman CW, Berchtold NC. Exercise: A behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002;25:295-301.  Back to cited text no. 6
[PUBMED]    
7.
O'Callaghan RM, Ohle R, Kelly AM. The effects of forced exercise on hippocampal plasticity in the rat: A comparison of LTP, spatial- and non-spatial learning. Behav Brain Res 2007;176:362-6.  Back to cited text no. 7
    
8.
Lee HH, Kim H, Lee JW, Kim YS, Yang HY, Chang HK, et al. Maternal swimming during pregnancy enhances short-term memory and neurogenesis in the hippocampus of rat pups. Brain Dev 2006;28:147-54.  Back to cited text no. 8
[PUBMED]    
9.
Kim H, Lee SH, Kim SS, Yoo JH, Kim CJ. The influence of maternal treadmill running during pregnancy on short-term memory and hippocampal cell survival in rat pups. Int J Dev Neurosci 2007;25:243-9.  Back to cited text no. 9
[PUBMED]    
10.
Uysal N, Sisman AR, Dayi A, Aksu I, Cetin F, Gencoglu C, et al. Maternal exercise decreases maternal deprivation induced anxiety of pups and correlates to increased prefrontal cortex BDNF and VEGF. Neurosci Lett 2011;505:273-8.  Back to cited text no. 10
[PUBMED]    
11.
Aksu I, Baykara B, Ozbal S, Cetin F, Sisman AR, Dayi A, et al. Maternal treadmill exercise during pregnancy decreases anxiety and increases prefrontal cortex VEGF and BDNF levels of rat pups in early and late periods of life. Neurosci Lett 2012;516:221-5.  Back to cited text no. 11
[PUBMED]    
12.
Akhavan MM, Miladi-Gorji H, Emami-Abarghoie M, Safari M, Sadighi-Moghaddam B, Vafaei AA, et al. Maternal voluntary exercise during pregnancy enhances the spatial learning acquisition but not the retention of memory in rat pups via a TrkB-mediated mechanism: The role of hippocampal BDNF expression. Iran J Basic Med Sci 2013;16:955-61.  Back to cited text no. 12
    
13.
Rizi AA, Reisi P, Naghsh N. Effect of forced treadmill exercise and blocking of opioid receptors with naloxone on memory in male rats. Adv Biomed Res 2016;5:20.  Back to cited text no. 13
[PUBMED]  [Full text]  
14.
Abiri H, Salmani ME, Sharafi S, Pajand P, Goudarzi I, Abrari K. Differential effect of swimming stress and exercise models in pentylenetetrazol induced kindling of rats. Zahedan J Res Med Sci 2014;16:65-69.  Back to cited text no. 14
    
15.
Kim TW, Ji ES, Kim TW, Lee SW, Lee CY, Lee SJ. Postnatal treadmill exercise attenuates prenatal stress-induced apoptosis through enhancing serotonin expression in aged-offspring rats. J Exerc Rehabil 2015;11:12-9.  Back to cited text no. 15
[PUBMED]    
16.
Robinson AM, Bucci DJ. Maternal exercise and cognitive functions of the offspring. Cogn Sci (Hauppauge) 2012;7:187-205.  Back to cited text no. 16
[PUBMED]    
17.
Park CY, Lee SH, Kim BK, Shin MS, Kim CJ, Kim H. Treadmill exercise ameliorates impairment of spatial learning ability through enhancing dopamine expression in hypoxic ischemia brain injury in neonatal rats. J Exerc Rehabil 2013;9:406-12.  Back to cited text no. 17
[PUBMED]    
18.
Hagg T. From neurotransmitters to neurotrophic factors to neurogenesis. Neuroscientist 2009;15:20-7.  Back to cited text no. 18
[PUBMED]    
19.
Yang P, Arnold SA, Habas A, Hetman M, Hagg T. Ciliary neurotrophic factor mediates dopamine D2 receptor-induced CNS neurogenesis in adult mice. J Neurosci 2008;28:2231-41.  Back to cited text no. 19
[PUBMED]    
20.
Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: News from mouse molecular genetics. Nat Rev Neurosci 2003;4:1002-12.  Back to cited text no. 20
    
21.
Whitaker-Azmitia PM. Serotonin and brain development: Role in human developmental diseases. Brain Res Bull 2001;56:479-85.  Back to cited text no. 21
[PUBMED]    
22.
Benninghoff J, van der Ven A, Schloesser RJ, Moessner R, Möller HJ, Rujescu D. The complex role of the serotonin transporter in adult neurogenesis and neuroplasticity. A critical review. World J Biol Psychiatry 2012;13:240-7.  Back to cited text no. 22
    
23.
Borta A, Höglinger GU. Dopamine and adult neurogenesis. J Neurochem 2007;100:587-95.  Back to cited text no. 23
    
24.
Banasr M, Hery M, Printemps R, Daszuta A. Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 2004;29:450-60.  Back to cited text no. 24
[PUBMED]    
25.
Leysen JE. 5-HT2 receptors. Curr Drug Targets CNS Neurol Disord 2004;3:11-26.  Back to cited text no. 25
[PUBMED]    
26.
Leknes S, Tracey I. A common neurobiology for pain and pleasure. Nat Rev Neurosci 2008;9:314-20.  Back to cited text no. 26
[PUBMED]    
27.
Jafary L, Reisi P, Naghsh N. Effects of fluoxetine on memory under forced treadmill exercise conditions in male rats. Adv Biomed Res 2015;4:235.  Back to cited text no. 27
[PUBMED]  [Full text]  
28.
Motaghinejad M, Ghaleni MA, Motaghinejad O. Preventive effects of forced exercise against alcohol-induced physical dependency and reduction of pain perception threshold. Int J Prev Med 2014;5:1299-307.  Back to cited text no. 28
[PUBMED]    
29.
Motaghinejad M, Motevalian M, Larijani SF, Khajehamedi Z. Protective effects of forced exercise against methylphenidate-induced anxiety, depression and cognition impairment in rat. Adv Biomed Res 2015;4:134.  Back to cited text no. 29
[PUBMED]  [Full text]  
30.
Shojaii A, Motaghinejad M, Norouzi S, Motevalian M. Evaluation of anti-inflammatory and analgesic activity of the extract and fractions of astragalus hamosus in animal models. Iran J Pharm Res 2015;14:263-9.  Back to cited text no. 30
[PUBMED]    
31.
Motaghinejad M, Ebrahimzadeh A, Shabab B. Preventive effect of central administration of venlafaxine on morphine physical dependence, nociception, and blood cortisol level in rat. Int J Prev Med 2014;5:1422-31.  Back to cited text no. 31
[PUBMED]    
32.
Herring A, Donath A, Yarmolenko M, Uslar E, Conzen C, Kanakis D, et al. Exercise during pregnancy mitigates Alzheimer-like pathology in mouse offspring. FASEB J 2012;26:117-28.  Back to cited text no. 32
[PUBMED]    
33.
Galdino GS, Duarte ID, Perez AC. Participation of endogenous opioids in the antinociception induced by resistance exercise in rats. Braz J Med Biol Res 2010;43:906-9.  Back to cited text no. 33
[PUBMED]    
34.
Wood PB. Role of central dopamine in pain and analgesia. Expert Rev Neurother 2008;8:781-97.  Back to cited text no. 34
[PUBMED]    
35.
Treister R, Pud D, Ebstein RP, Laiba E, Raz Y, Gershon E, et al. Association between polymorphisms in serotonin and dopamine-related genes and endogenous pain modulation. J Pain 2011;12:875-83.  Back to cited text no. 35
[PUBMED]    
36.
Shankarappa SA, Piedras-Rentería ES, Stubbs EB Jr. Forced-exercise delays neuropathic pain in experimental diabetes: Effects on voltage-activated calcium channels. J Neurochem 2011; 118:224-36.  Back to cited text no. 36
    
37.
Gleeson M. Immune Function in Sport and Exercise. J Appl Physiol 2007; 103:693-699.  Back to cited text no. 37
[PUBMED]    
38.
Vega CC, Reyes-Castro LA, Bautista CJ, Larrea F, Nathanielsz PW, Zambrano E. Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism. Int J Obes (Lond) 2015;39:712-9.  Back to cited text no. 38
[PUBMED]    
39.
Field T, Hernandez-Reif M, Diego M, Schanberg S, Kuhn C. Cortisol decreases and serotonin and dopamine increase following massage therapy. Int J Neurosci 2005;115:1397-413.  Back to cited text no. 39
[PUBMED]    
40.
Zhao ZQ, Chiechio S, Sun YG, Zhang KH, Zhao CS, Scott M, et al. Mice lacking central serotonergic neurons show enhanced inflammatory pain and an impaired analgesic response to antidepressant drugs. J Neurosci 2007;27:6045-53.  Back to cited text no. 40
[PUBMED]    
41.
Zakaria ZA, Sulaiman MR, Mat Jais AM, Somchit MN. Effect of various antagonists on the Channa striatus fillet extract antinociception in mice. Can J Physiol Pharmacol 2005;83:635-42.  Back to cited text no. 41
[PUBMED]    
42.
Jensen RV, Gullans SR, Sarang SS, Yoshida T, Cadet R, Valeras AS. Discovery of molecular mechanisms of neuroprotection. J Neurosci 2008;28:9473-85.  Back to cited text no. 42
    
43.
Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology 2006;66:17-22.  Back to cited text no. 43
[PUBMED]    
44.
Potvin S, Grignon S, Marchand S. Human evidence of a supra-spinal modulating role of dopamine on pain perception. Synapse 2009;63:390-402.  Back to cited text no. 44
[PUBMED]    
45.
Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med 2009;60:355-66.  Back to cited text no. 45
[PUBMED]    
46.
Foley TE, Fleshner M. Neuroplasticity of dopamine circuits after exercise: Implications for central fatigue. Neuromolecular Med 2008;10:67-80.  Back to cited text no. 46
[PUBMED]    
47.
Lan X, Zhang M, Yang W, Zheng Z, Wu Y, Zeng Q, et al. Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion. Neurol Sci 2014;35:761-6.  Back to cited text no. 47
[PUBMED]    
48.
Ma Q, Wang J, Chen XW, An GH, Liu HT. Alterations in rat hippocampal norepinephrine and serotonin levels under physical exercise and psychological stress. Chin J Pathophysiol 2008;8:23.  Back to cited text no. 48