Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
Department of Pharmacology, Hamadan University of medical sciences, Hamadan, Iran.
Aims: Various evidences have shown the effect of ovarian hormones on locomotor activities and catalepsy induced by a variety of stimuli. The aim of this study was to evaluate the effects of estrogen and progesterone on catalepsy and motor and balance impairment classified as haloperidol-induced extrapyramidal disorders.
Materials and Methods: The current experimental study was performed on 96 female Wistar rats (180-200g). These rats were randomly divided into 16 groups (n=6). Prior to administration of haloperidol, the rats were pretreated with flutamide (10mg/kg, i.p.), estrogen (1mg/kg 17 β-estradiol, s.c.), and/or progesterone (1mg/kg, i.p.) for 1 day or 7 consecutive days. The effects of estrogen and progesterone on haloperidol-induced catalepsy and motor impairment were assessed by a bar test and a rotarod performance test, respectively. Data were analyzed by SPSS 22 software using ANCOVA and Tukey test.
Findings: One to 7-day treatment with estrogen had a protective effect on haloperidol-induced extrapyramidal disorders such that it significantly improved catalepsy and motor impairment in the rats and restored and normalized their motor levels. However, the progesterone administration did not represent significant effects in improving extrapyramidal symptoms and a slight improvement was achieved. The co-administration of flutamide significantly reduced the protective effect of estrogen on catalepsy and motor balance impairment induced by haloperidol.
Conclusion: The deficiency of ovarian hormones increases catalepsy; however, this disorder is more likely to occur due to estrogen insufficiency. Hence, progesterone plays a little role in it. Moreover, the anti-cataleptic effect of ovarian hormones is exerted through affecting androgenic receptors.
- De Lau LM, Breteler MM. Epidemiology of Parkinson's disease. Lancet Neurol. 2006;5(6):525-35. [DOI:10.1016/S1474-4422(06)70471-9]
- Rahimmi A, Khosrobakhsh F, Izadpanah E, Hassanzadeh K. Induction of Parkinson's disease model in rat by rotenone. J Isfahan Med Sch. 2014;32(296):1250-58.
- Sharifi H, Nayebi AM, Farajnia S, Haddadi R. Effect of chronic administration of buspirone and fluoxetine on inflammatory cytokines in 6-Hydroxydopamine-lesioned rats. Drug Res (Stuttg). 2015;65(8):393-7. [DOI:10.1055/s-0034-1374615] [PMID]
- Honma T, Fukushima H. Effects of bilateral lesions in the striatum or nucleus accumbens on the cataleptogenic activity of neuroleptics in rats. Jpn J Pharmacol. 1978;28(2):231-8. [DOI:10.1254/jjp.28.231] [PMID]
- Wei L, Chen L. Effects of 5-HT in globus pallidus on haloperidol-induced catalepsy in rats. Neurosci Lett. 2009;454(1):49-52. [DOI:10.1016/j.neulet.2009.02.053] [PMID]
- Kurz M, Hummer M, Oberbauer H, Fleischhacker WW. Extrapyramidal side effects of clozapine and haloperidol. Psychopharmacology(Berl). 1995;118(1):52-6. [DOI:10.1007/BF02245249] [PMID]
- Dunstan R, Broekkamp CL, Lloyd KG. Involvement of caudate nucleus, amygdala or reticular formation in neuroleptic and narcotic catalepsy. Pharmacol Biochem Behav. 1981;14(2):169-74. [DOI:10.1016/0091-3057(81)90239-2]
- Marceglia S, Priori A. Sex, genes, hormones and nigral neurodegeneration: Two different Parkinson's diseases in males and in females. 2007;2(5):499-503. [DOI:10.2217/14796708.2.5.499]
- Munro CA, McCaul ME, Wong DF, Oswald LM, Zhou Y, Brasic J, et al. Sex differences in striatal dopamine release in healthy adults. Biol Psychiatry. 2006;59(10):966-74. [DOI:10.1016/j.biopsych.2006.01.008] [PMID]
- Nicoletti F, Ferrara N, Patti F, Viglianesi M, Rampello L, Bianchi A, et al. Influence of sex steroids and prolactin on haloperidol-induced catalepsy. Brain Res. 1983;279(1-2):352-8. [DOI:10.1016/0006-8993(83)90209-3]
- Haddadi R, Mohajjel Nayebi A, Brooshghalan SE. Pretreatment with silymarin reduces brain myeloperoxidase activity and inflammatory cytokines in 6-OHDA hemi-parkinsonian rats. Neurosci Lett. 2013;555:106-11. [DOI:10.1016/j.neulet.2013.09.022] [PMID]
- Kheradmand A, Mohajjel Nayebi A, Jorjani M, Haddadi R. Effect of WR-1065 on 6-hydroxydopamineinduced catalepsy and IL-6 level in rats. Iran J Basic Med Sci. 2016;19(5):490-6.
- Haddadi R, Nayebi AM, Farajniya S, Brooshghalan SE, Sharifi H. Silymarin improved 6-OHDA-induced motor impairment in hemi-parkisonian rats: Behavioral and molecular study. Daru. 2014;22:38. [DOI:10.1186/2008-2231-22-38] [PMID]
- Kheradmand A, Nayebi AM, Jorjani M, Khalifeh S, Haddadi R. Effects of WR1065 on 6-hydroxydopamineinduced motor imbalance: Possible involvement of oxidative stress and inflammatory cytokines. Neurosci Lett. 2016;627:7-12. [DOI:10.1016/j.neulet.2016.05.040] [PMID]
- Haddadi R, Eyvari Brooshghalan S, Farajniya S, Mohajjel Nayebi A, Sharifi H. Short-term treatment with silymarin improved 6-OHDA-induced catalepsy and motor imbalance in Hemi-parkisonian rats. Adv Pharm Bull. 2015;5(4):463-9. [DOI:10.15171/apb.2015.063] [PMID]
- Lyons KE, Hubble JP, Tröster AI, Pahwa R, Koller WC. Gender differences in Parkinson's disease. Clin Neuropharmacol. 1998;21(2):118-21.
- Field EF, Whishaw IQ, Pellis SM. Sex differences in catalepsy: Evidence for hormone-dependent postural mechanisms in haloperidol-treated rats. Behav Brain Res. 2000;109(2):207-12. [DOI:10.1016/S0166-4328(99)00174-6]
- Ragonese P, D'amelio M, Salemi G, Aridon P, Gammino M, Epifanio A, et al. Risk of Parkinson disease in women: Effect of reproductive characteristics. Neurology. 2004;62(11):2010-4. [DOI:10.1212/WNL.62.11.2010] [PMID]
- Dluzen D, Horstink M. Estrogen as neuroprotectant of nigrostriatal dopaminergic system: Laboratory and clinical studies. Endocrine. 2003;21(1):67-75. [DOI:10.1385/ENDO:21:1:67]
- Strijks E, Kremer JA, Horstink MW. Effects of female sex steroids on Parkinson's disease in postmenopausal women. Clin Neuropharmacol. 1999;22(2):93-7. [DOI:10.1097/00002826-199903000-00005] [PMID]
- Palermo-Neto J, Dorce VA. Influences of estrogen nd/or progesterone on some dopamine related behavior in rats. Gen Pharmacol. 1990;21(1):83-7. [DOI:10.1016/0306-3623(90)90600-Q]
- Baines H, Nwagwu MO, Furneaux EC, Stewart J, Kerr JB, Mayhew TM, et al. Estrogenic induction of spermatogenesis in the hypogonadal (hpg) mouse: Role of androgens. Reproduction. 2005;130(5):643-54. [DOI:10.1530/rep.1.00693] [PMID]
- Handa RJ, Stadelman HL, Resko JA. Effect of estrogen on androgen receptor dynamics in female rat pituitary. Endocrinology. 1987;121(1):84-9. [DOI:10.1210/endo-121-1-84] [PMID]
- Fujimoto J, Nishigaki M, Hori M, Ichigo S, Itoh T, Tamaya T. The effect of estrogen and androgen on androgen receptors and mRNA levels in uterine leiomyoma, myometrium and endometrium of human subjects. J Steroid Biochem Mol Biol. 1994;50(3-4):137-43. [DOI:10.1016/0960-0760(94)90020-5]