@2024 Afarand., IRAN
ISSN: 2252-0805 The Horizon of Medical Sciences 2014;20(3):179-184
ISSN: 2252-0805 The Horizon of Medical Sciences 2014;20(3):179-184
Simultaneous Effect of Progesterone Usage and Exercise on Anxiety in Ovariectomized Rats
ARTICLE INFO
Article Type
Original ResearchAuthors
Karimipour A. (1 )Abbasnejad M. (1 )
Kesmati M. (2 )
Sofiabadi M. (* )
(* ) Physiology Department, Medicine Faculty, Qazvin University of Medical Sciences, Qazvin, Iran
(1 ) Biology Department, Science Faculty, Shahid Bahonar University, Kerman, Iran
(2 ) Biology Department, Science Faculty, Shahid Chamran University, Ahvaz, Iran
Correspondence
Address: Physiology Department, Shahid Baba’ei Medical Faculty, Qazvin University of Medical Sciences, Shahid Bahonar Street, Qazvin, Iran. Postal Code: 3419759811Phone: +982833336001
Fax: +982833324970
mohasofi@yahoo.com
Article History
Received: April 10, 2014Accepted: April 23, 2014
ePublished: September 23, 2014
ABSTRACT
Aims
Sex hormones and exercise may influence anxiety, individually. This study was done to
investigate the effect of exercise and progesterone on anxiety in ovariectomized female rats.
Materials & Methods In this experimental study, 40 adult female Wistar rats weighting 200±20gr were used. They were ovarectomized after anesthesia. They were randomly divided to five groups including control (no treatment), sesame oil, exercise and sesame oil, progesterone (8mg/kg), progesterone and exercise. 30min after intraperitoneally injection of the vehicle or progesterone or before exercise the percentage of animal enterance to the open arms and the percentage of time spent in the open arms were measured.
Findings Intraperitoneally injection of progesterone (8mg/kg) reduced the mean percentage of open arms entries and the average percentage of time spent in the open arms compared to control group (p<0.05). Doing exercises before injection of progesterone inhibited both progesterone-induced anxiety related symptoms.
Conclusion Administration of pharmacological doses of the progesterone hormone increases anxiety and physical activity can reduce this effect.
Materials & Methods In this experimental study, 40 adult female Wistar rats weighting 200±20gr were used. They were ovarectomized after anesthesia. They were randomly divided to five groups including control (no treatment), sesame oil, exercise and sesame oil, progesterone (8mg/kg), progesterone and exercise. 30min after intraperitoneally injection of the vehicle or progesterone or before exercise the percentage of animal enterance to the open arms and the percentage of time spent in the open arms were measured.
Findings Intraperitoneally injection of progesterone (8mg/kg) reduced the mean percentage of open arms entries and the average percentage of time spent in the open arms compared to control group (p<0.05). Doing exercises before injection of progesterone inhibited both progesterone-induced anxiety related symptoms.
Conclusion Administration of pharmacological doses of the progesterone hormone increases anxiety and physical activity can reduce this effect.
CITATION LINKS
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[7]Frye CA, Walf AA, Paris JJ. Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation of 5alpha-reduced progestogens and reduces anxiety-like behavior of middle-aged rats. Behav Pharmacol. 2010;21(5-6):530-9.
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[9]Beckley EH, Scibelli AC, Finn DA. Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability. Psychoneuroendocrinology. 2011;36(6):824-33.
[10]Lagunas N, Calmarza-Font I, Diz-Chaves Y, Garcia-Segura LM. Long-term ovariectomy enhances anxiety and depressive-like behaviors in mice submitted to chronic unpredictable stress. Horm Behav. 2010;58(5):786-91.
[11]Andréen L, Nyberg S, Turkmen S, van Wingen G, Fernández G, Bäckström T. Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators. Psychoneuroendocrinology. 2009;34(8):1121-32.
[12]Schüle C, Nothdurfter C, Rupprecht R. The role of allopregnanolone in depression and anxiety. Prog Neurobiol. 2014;113:79-87.
[13]Galeeva AY, Pivina SG, Tuohimaa P, Ordyan NE. Involvement of nuclear progesterone receptors in the formation of anxiety in female mice. Neurosci Behav Physiol. 2007;37(8):843-8.
[14]Mello MT, Boscolo RA, Esteves AM, Tufik S. Physical exercise and psychological aspects. Rev Bras Med Esporte. 2005;11(3):203-207.
[15]Garwin AW, Koltyn KF, Morgan WP. Influence of acute physical activity and relaxation on state anxiety and blood lactate in untrained college males. Int J Sports Med. 1997;18(6):470-6.
[16]OConnor PJ, Petruzzello SJ, Kubitz KA, Robinson TL. Anxiety responses to maximal exercise testing. Br J Sports Med. 1995;29(2):97-102.
[17]Parker AG, Hetrick SE, Jorm AF, Yung AR, McGorry PD, Mackinnon A, et al. The effectiveness of simple psychological and exercise interventions for high prevalence mental health problems in young people: A factorial randomized controlled trial. Trials. 2011;12:76.
[18]Leasure JL, Jones M. Forced and voluntary exercise differentially affect brain and behavior. Neuroscience. 2008;156(3):456-65.
[19]Starkey NJ, Bridges NJ. The effects of acute, chronic and withdrawn progesterone in male and female Mongolian gerbils (Meriones unguiculatus) in two tests of anxiety. Behav Brain Res. 2009;207(2):490-9.
[20]Wali B, Ishrat T, Won S, Stein DG, Sayeed I. Progesterone in experimental permanent stroke: A dose-response and therapeutic time-window study. Brain. 2014;137(Pt 2):486-502.
[21]Hichri O, Laurin JC, Julien CA, Joseph V, Bairam A. Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats. Adv Exp Med Biol. 2012;758:43-8.
[22]Sharp K, Brindle PM, Brown MW, Turner GM. Memory loss during pregnancy. Int J Obstet Gynaecol. 1993;100(3):209-15.
[23]Sofi abadi M, Sadeghipour H, Shabanzadeh A, Zarindast M, Dehpour A. Possible involvement of nitric oxide (NO) in anxiety-like behavior induced by female steroid hormones. koomesh. 2001;2(3):177-83.
[24]Galeeva A, Tuohimaa P. Analysis of mouse plus-maze behavior modulated by ovarian steroids. Behav Brain Res. 2001;119(1):41-7.
[25]Bitran D, Hilvers RJ, Kellogg CK. Anxiolytic effects of 3α-hydroxy-5α[β]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor. Brain Res. 1991;561(1):157-61.
[26]de Chaves G, Moretti M, Castro AA, Dagostin W, da Silva GG, Boeck CR, et al. Effects of long-term ovariectomy on anxiety and behavioral despair in rats. Physiol Behav. 2009;97(3-4):420-5.
[27]Hu ZY, Bourreau E, Jung-Testas I, Robel P, Baulieu EE. Neurosteroids: Oligodendrocyte mitochondria convert cholesterol to pregnenolone. Proc Natl Acad Sci. 1987;84(23):8215-19.
[28]N-Wihlbäck AC, Sundström-Poromaa I, Bäckström T. Action by and sensitivity to neuroactive steroids in menstrual cycle related CNS disorders. Psychopharmacology. 2006;186(3):388-401.
[29]Genazzani AR, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, et al. Circulating levels of allopregnanolone in humans: Gender, age, and endocrine influences. J Clin Endocrinol Metab. 1998;83(6):2099-103.
[30]Sadeghipour HR, Ghasemi M, Sadeghipour H, Riazi K, Soufiabadi M, Fallahi N, et al. Nitric oxide involvement in estrous cycle-dependent changes of the behavioral responses of female rats in the elevated plus-maze test. Behav Brain Res. 2007;178(1):10-7.
[31]Gulinello M, Gong QH, Li X, Smith SS. Short-term exposure to a neuroactive-steroid increases alpha4 GABA (A) receptor subunit levels in association with increased anxiety in the female rat. Brain Res. 2001;910(1-2):55-66.
[32]Concas A, Serra M, Atsoggiu T, Biggio G. Foot-shock stress and anxiogenic beta-carbolines increase t-[35S]butylbicyclophosphorothionate binding in the rat cerebral cortex, an effect opposite to anxiolytics and gamma-aminobutyric acid mimetics. J Neurochem. 1988;51(6):1868-76.
[33]Miczek KA, Fish EW, De Bold JF. Neurosteroids, GABAA receptors, and escalated aggressive behavior. Horm Behav. 2003;44(3):242-57.
[34]Wang M, Bäckström T, Sundström I, Wahlström G, Olsson T, Zhu D, et al. Neuroactive-steroids and central nervous system disorders. Int Rev Neurobiol. 2001;46:421-59.
[35]Björn I, Bixo M, Nöjd KS, Collberg P, Nyberg S, Sundström-Poromaa I, et al. The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy. Gynecol Endocrinol. 2002;16(1):1-8.
[36]Andréen L, Bixo M, Nyberg S, Sundström-Poromaa I, Bäckström T. Progesterone effects during sequential hormone replacement therapy. Eur J Endocrinol. 2003;148(3):571-7.
[37]Deuster PA, Petrides JS, Singh A, Lucci EB, Chrousos GP, Gold PW. High intensity exercise promotes escape of adrenocorticotropin and cortisol from suppression by dexamethasone: Sexually dimorphic responses. J Clin Endocrinol Metab. 1998;83(9):3332-8.
[38]Dunn AL, Trivedi MH, O'Neal HA. Physical activity dose-response effects on outcomes of depression and anxiety. Med Sci Sports Exerc. 2001;33(6 Suppl):587-97.
[39]Paluska SA, Schwenk TL. Physical activity and mental health: Current concepts. Sports Med. 2000;29(3):167-80.
[40]Moriyama CK, Oneda B, Bernardo FR, Cardoso CG Jr, Forjaz CL, Abrahao SB, et al. A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women. Menopause. 2008;15(4 Pt 1):613-8.
[41]Coombes JS, Law J, Lancashire B, Fassett RG. Exercise is medicine: Curbing the burden of chronic disease and physical inactivity. Asia Pac J Public Health. 2013;25(1):161-6.
[42]Raglin JS, Wilson M. State anxiety following 20 minutes of bicycle ergometer exercise at selected intensities. Int J Sports Med. 1996;17(6):467-71.
[43]Frisch RE, Snow RC, Johnson LA, Gerard B, Barbieri R, Rosen B. Magnetic resonance imaging of overall and regional body fat, estrogen metabolism, and ovulation of athletes compared to controls. J Clin Endocrinol Metab. 1993;77(2):471-7.
[44]Kramer JM, Beatty JA, Little HR, Plowey ED, Waldrop TG. Chronic exercise alters caudal hypothalamic regulation of the cardiovascular system in hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2001;280(2):389-97.
[45]Bhatnagar S, Nowak N, Babich L, Bok L. Deletion of the 5-HT3 receptor differentially affects behavior of males and females in the Porsolt forced swim and defensive withdrawal tests. Behav Brain Res. 2004;153(2):527-35.
[46]Farrell PA, Gustafson AB, Morgan WP, Pert CB. Enkephalins, catecholamines, and psychological mood alterations: effects of prolonged exercise. Med Sci Sports Exerc. 1987;19(4):347-53.
[47]Chaouloff F. Effects of acute physical exercise on central serotonergic systems. Med Sci Sports Exerc. 1997;29(1):58-62.
[2]Craske MG, Rauch SL, Ursano R, Prenoveau J, Pine DS, Zinbarg RE. What is an anxiety disorder?. Focus. 2009;9(3):369-388.
[3]Steimer T. The biology of fear- and anxiety-related behaviors. Dialogues Clin Neurosci. 2002;4(3):231-49.
[4]Clement Y, chapouthier G. Biological bases of anxiety. Neurosci Biobehav Rev. 1998;22(5):623-33.
[5]Brawman-Mintzer O, Lydiard RB. Biological basis of generalized anxiety disorder. J Clin Psychiatry. 1997;58(Suppl 3):16-25.
[6]Landgraf R, Wigger A. Born to be anxious: Neuroendocrine and genetic correlates of trait anxiety in HAB rats. Stress. 2003;6(2):111-9.
[7]Frye CA, Walf AA, Paris JJ. Conjugated equine estrogen, with medroxyprogesterone acetate, enhances formation of 5alpha-reduced progestogens and reduces anxiety-like behavior of middle-aged rats. Behav Pharmacol. 2010;21(5-6):530-9.
[8]Mueller SC, Grissom EM, Dohanich GP. Assessing gonadal hormone contributions to affective psychopathologies across humans and animal models. Psychoneuroendocrinology. 2014;46:114-28.
[9]Beckley EH, Scibelli AC, Finn DA. Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability. Psychoneuroendocrinology. 2011;36(6):824-33.
[10]Lagunas N, Calmarza-Font I, Diz-Chaves Y, Garcia-Segura LM. Long-term ovariectomy enhances anxiety and depressive-like behaviors in mice submitted to chronic unpredictable stress. Horm Behav. 2010;58(5):786-91.
[11]Andréen L, Nyberg S, Turkmen S, van Wingen G, Fernández G, Bäckström T. Sex steroid induced negative mood may be explained by the paradoxical effect mediated by GABAA modulators. Psychoneuroendocrinology. 2009;34(8):1121-32.
[12]Schüle C, Nothdurfter C, Rupprecht R. The role of allopregnanolone in depression and anxiety. Prog Neurobiol. 2014;113:79-87.
[13]Galeeva AY, Pivina SG, Tuohimaa P, Ordyan NE. Involvement of nuclear progesterone receptors in the formation of anxiety in female mice. Neurosci Behav Physiol. 2007;37(8):843-8.
[14]Mello MT, Boscolo RA, Esteves AM, Tufik S. Physical exercise and psychological aspects. Rev Bras Med Esporte. 2005;11(3):203-207.
[15]Garwin AW, Koltyn KF, Morgan WP. Influence of acute physical activity and relaxation on state anxiety and blood lactate in untrained college males. Int J Sports Med. 1997;18(6):470-6.
[16]OConnor PJ, Petruzzello SJ, Kubitz KA, Robinson TL. Anxiety responses to maximal exercise testing. Br J Sports Med. 1995;29(2):97-102.
[17]Parker AG, Hetrick SE, Jorm AF, Yung AR, McGorry PD, Mackinnon A, et al. The effectiveness of simple psychological and exercise interventions for high prevalence mental health problems in young people: A factorial randomized controlled trial. Trials. 2011;12:76.
[18]Leasure JL, Jones M. Forced and voluntary exercise differentially affect brain and behavior. Neuroscience. 2008;156(3):456-65.
[19]Starkey NJ, Bridges NJ. The effects of acute, chronic and withdrawn progesterone in male and female Mongolian gerbils (Meriones unguiculatus) in two tests of anxiety. Behav Brain Res. 2009;207(2):490-9.
[20]Wali B, Ishrat T, Won S, Stein DG, Sayeed I. Progesterone in experimental permanent stroke: A dose-response and therapeutic time-window study. Brain. 2014;137(Pt 2):486-502.
[21]Hichri O, Laurin JC, Julien CA, Joseph V, Bairam A. Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats. Adv Exp Med Biol. 2012;758:43-8.
[22]Sharp K, Brindle PM, Brown MW, Turner GM. Memory loss during pregnancy. Int J Obstet Gynaecol. 1993;100(3):209-15.
[23]Sofi abadi M, Sadeghipour H, Shabanzadeh A, Zarindast M, Dehpour A. Possible involvement of nitric oxide (NO) in anxiety-like behavior induced by female steroid hormones. koomesh. 2001;2(3):177-83.
[24]Galeeva A, Tuohimaa P. Analysis of mouse plus-maze behavior modulated by ovarian steroids. Behav Brain Res. 2001;119(1):41-7.
[25]Bitran D, Hilvers RJ, Kellogg CK. Anxiolytic effects of 3α-hydroxy-5α[β]-pregnan-20-one: endogenous metabolites of progesterone that are active at the GABAA receptor. Brain Res. 1991;561(1):157-61.
[26]de Chaves G, Moretti M, Castro AA, Dagostin W, da Silva GG, Boeck CR, et al. Effects of long-term ovariectomy on anxiety and behavioral despair in rats. Physiol Behav. 2009;97(3-4):420-5.
[27]Hu ZY, Bourreau E, Jung-Testas I, Robel P, Baulieu EE. Neurosteroids: Oligodendrocyte mitochondria convert cholesterol to pregnenolone. Proc Natl Acad Sci. 1987;84(23):8215-19.
[28]N-Wihlbäck AC, Sundström-Poromaa I, Bäckström T. Action by and sensitivity to neuroactive steroids in menstrual cycle related CNS disorders. Psychopharmacology. 2006;186(3):388-401.
[29]Genazzani AR, Petraglia F, Bernardi F, Casarosa E, Salvestroni C, Tonetti A, et al. Circulating levels of allopregnanolone in humans: Gender, age, and endocrine influences. J Clin Endocrinol Metab. 1998;83(6):2099-103.
[30]Sadeghipour HR, Ghasemi M, Sadeghipour H, Riazi K, Soufiabadi M, Fallahi N, et al. Nitric oxide involvement in estrous cycle-dependent changes of the behavioral responses of female rats in the elevated plus-maze test. Behav Brain Res. 2007;178(1):10-7.
[31]Gulinello M, Gong QH, Li X, Smith SS. Short-term exposure to a neuroactive-steroid increases alpha4 GABA (A) receptor subunit levels in association with increased anxiety in the female rat. Brain Res. 2001;910(1-2):55-66.
[32]Concas A, Serra M, Atsoggiu T, Biggio G. Foot-shock stress and anxiogenic beta-carbolines increase t-[35S]butylbicyclophosphorothionate binding in the rat cerebral cortex, an effect opposite to anxiolytics and gamma-aminobutyric acid mimetics. J Neurochem. 1988;51(6):1868-76.
[33]Miczek KA, Fish EW, De Bold JF. Neurosteroids, GABAA receptors, and escalated aggressive behavior. Horm Behav. 2003;44(3):242-57.
[34]Wang M, Bäckström T, Sundström I, Wahlström G, Olsson T, Zhu D, et al. Neuroactive-steroids and central nervous system disorders. Int Rev Neurobiol. 2001;46:421-59.
[35]Björn I, Bixo M, Nöjd KS, Collberg P, Nyberg S, Sundström-Poromaa I, et al. The impact of different doses of medroxyprogesterone acetate on mood symptoms in sequential hormonal therapy. Gynecol Endocrinol. 2002;16(1):1-8.
[36]Andréen L, Bixo M, Nyberg S, Sundström-Poromaa I, Bäckström T. Progesterone effects during sequential hormone replacement therapy. Eur J Endocrinol. 2003;148(3):571-7.
[37]Deuster PA, Petrides JS, Singh A, Lucci EB, Chrousos GP, Gold PW. High intensity exercise promotes escape of adrenocorticotropin and cortisol from suppression by dexamethasone: Sexually dimorphic responses. J Clin Endocrinol Metab. 1998;83(9):3332-8.
[38]Dunn AL, Trivedi MH, O'Neal HA. Physical activity dose-response effects on outcomes of depression and anxiety. Med Sci Sports Exerc. 2001;33(6 Suppl):587-97.
[39]Paluska SA, Schwenk TL. Physical activity and mental health: Current concepts. Sports Med. 2000;29(3):167-80.
[40]Moriyama CK, Oneda B, Bernardo FR, Cardoso CG Jr, Forjaz CL, Abrahao SB, et al. A randomized, placebo-controlled trial of the effects of physical exercises and estrogen therapy on health-related quality of life in postmenopausal women. Menopause. 2008;15(4 Pt 1):613-8.
[41]Coombes JS, Law J, Lancashire B, Fassett RG. Exercise is medicine: Curbing the burden of chronic disease and physical inactivity. Asia Pac J Public Health. 2013;25(1):161-6.
[42]Raglin JS, Wilson M. State anxiety following 20 minutes of bicycle ergometer exercise at selected intensities. Int J Sports Med. 1996;17(6):467-71.
[43]Frisch RE, Snow RC, Johnson LA, Gerard B, Barbieri R, Rosen B. Magnetic resonance imaging of overall and regional body fat, estrogen metabolism, and ovulation of athletes compared to controls. J Clin Endocrinol Metab. 1993;77(2):471-7.
[44]Kramer JM, Beatty JA, Little HR, Plowey ED, Waldrop TG. Chronic exercise alters caudal hypothalamic regulation of the cardiovascular system in hypertensive rats. Am J Physiol Regul Integr Comp Physiol. 2001;280(2):389-97.
[45]Bhatnagar S, Nowak N, Babich L, Bok L. Deletion of the 5-HT3 receptor differentially affects behavior of males and females in the Porsolt forced swim and defensive withdrawal tests. Behav Brain Res. 2004;153(2):527-35.
[46]Farrell PA, Gustafson AB, Morgan WP, Pert CB. Enkephalins, catecholamines, and psychological mood alterations: effects of prolonged exercise. Med Sci Sports Exerc. 1987;19(4):347-53.
[47]Chaouloff F. Effects of acute physical exercise on central serotonergic systems. Med Sci Sports Exerc. 1997;29(1):58-62.