Effect of Dexamethasone on Striatal Neurotransmissions in the Rats Subjected to Parkinson’s Disease Animal Model

Document Type : Original Article


1 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 R and D and QC consultant & Hepatitis and AIDS Department, Research and Production Complex, Pasteur Institute of Iran, Tehran, Iran

3 Department of Physiology and Physiology Research Center, Jundishapour University of Medical Sciences, Ahvaz, Iran

4 Department of Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran


The aim of this study was to evaluate the effects of dexamethasone on striatal dopaminergic, glutamatergic and gamma amino butyric acid (GABA) ergic neurotransmission in normal and parkinsonian rats.
Materials and Methods
Dexamethasone (0.15, 0.30, 0.60 and 0.8 mg/kg) was administered to normal or parkinsonian rats (i.p.) followed by the analysis of the striatal neurotransmitters concentrations. Additionally, the effect of dexamethasone on the damaged Substantia nigra pars compata (SNc) neurons has been investigated.
Dexamethasone resulted in decreased level of striatum glutamatergic-GABAergic and enhanced dopaminergic neurotransmission in normal and parkinsonian rats. In addition, acute treatment with dexamethasone did not improve the lesion at all.
These findings suggest the new therapeutic mechanism of action for dexamethasone in Parkinson’s disease animal model.


1. Rowland LP. Inhibition of cyclooxygenase-2 protects motor neurons in an organotypic model of amyotrophic lateral sclerosis. Ann Neurol 2000; 48:792–795.
2. McGeer PL, McGeer EG. Innate immunity, local inflammation, and degenerative disease. Sci Aging Kowledge Environ 2002; 29 review 3.
3. McGeer PL, Schwab C, Parent A, Doudet D. Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine administration. Ann Neurol 2003; 54:599–604.
4. Smith WL, Marnett LJ, Dewitt DL.Prostaglandin and thromboxane biosynthesis. Pharmacol Ther 1991; 49:153-79.
5. Xie WL, Chipman GJ, Robertson DL, Erikson RL.Expression of a mitogenresponsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci USA 1991; 88:2692-2696.
6. Shaftel SS, Olschowka JA, Hurly SD. COX-3: a splice variant of cyclooxygenase-1 in mouse neural tissue and cells. Brain Res Mol Brain Res 2003; 119:153-179.
7. Herschman HR. Prostaglandin synthase-2. Biochem Biophys Acta 1996; 1299:153-179.
8. Dubois RN, Abramson SB, Crofford L, Cupta RA. Cyclooxygenase in biology and disease. FASEB J 1998; 12:1063-1073.
9. Li RC, Row BW, Gozal E, Fan Q, Guo SZ. Cyclooxygenase-2 and intermittent hypoxia-induced spatial defects in the rat. Am J Respir Crit Care Med 2003; 168:469-475.
10. Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain disease. J Neuropathol Exp Neural 2004; 63:901-910.
11. Kurkowska-Jastrzebska I, Litwin T, Joniec I, Ciesielska A, Przybylkowski A, Czlonkowski A. Dexamethasone protects against dopaminergic neuron damage in a mouse model of Parkinson’s disease. Int Immunopharmacol 2004; 4:1307-1318.
12. Sánchez-Pernaute R, Ferree A, Cooper O, Yu M, Brownell L, Isacson O. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease. J Neuroinflammation 2004; 1:6.
13. Mladenovic A, Perovic M, Raicevic N, Kanazir S, Rakic L, Ruzdijic S. 6- Hydroxydopamine increases the level of TNFalpha and bax mRNA in the striatum and induces apoptosis of dopaminergic neurons in hemiparkinsonian rats. Brain Res 2004; 996:237-245.
14. Shafiee Ardestani M, Mehrab H, Sadeghzadeh N. Effects of dexamethasone and betamethasone on rigidity in a rat model of Parkinson's disease. Indian J Pharmacol 2007; 39:235-239.
15. Shafiee Ardestani M, Hemmati AA, Fathi-Moghaddam H, Nazari Z. Effects of aspirin and celecoxib on rigidity in a rat model of Parkinson’s disease. Pak J Biol Sci 2007; 21:3853-3858.
16. Paxinos G,Watson C. The rat brain in stereotaxic coordinates. San Diego: Academic Press; 1997.
17. Fathi-Moghaddam H, Shafiee Ardestani, M, Saffari M, Navidpour L, Shafiee A, Rahmim A. Dopaminergic but not glutamatergic neurotransmission is increased in the striatum after selective COX-2 inhibition in normal and hemiparkinsonian rats. Basic Clin Pharmacol Toxicol 2008; 103:293-296.
18. Shafiee Ardestani M. Parkinson's disease, the inflammatory pathway and anti inflammatory agents: an overview. J Med Sci 2010; 10:49-58.
19. Kurkowska-Jastrzebska I, Litwin T, Joniec I, Ciesielska A, Przybylkowski A, Czlonkowski A, et al. Dexamethasone protects against dopaminergic neuron damage in a mouse model of Parkinson.s disease. Int Immunopharmacol 2004; 4:1307-1318.
20. Chopde CT, Hote MS, Mandhane SN, Muthal AV. Giucocorticoids attenuate haloperidoMnduced catalepsy through adrenal catecholamines. J Neural Transm (Gen Sect), 1995; 102:47-54.