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Adv Pharm Bull. 2017;7(3):359-365.
doi: 10.15171/apb.2017.043
PMID: 29071217
PMCID: PMC5651056
Scopus id: 85030115905
  Abstract View: 735
  PDF Download: 965

Research Article

Modafinil Improves Catalepsy in a Rat 6-Hydroxydopamine Model of Parkinson’s Disease; Possible Involvement of Dopaminergic Neurotransmission

Reza Vajdi-Hokmabad 1, Mojtaba Ziaee 2, Saeed Sadigh-Eteghad 3, Siamak Sandoghchian Shotorbani 4, Javad Mahmoudi 3 *

1 Department of veterinary, Miyaneh branch, Islamic Azad University, Miyaneh, Iran.
2 Medicinal Plant Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran.
3 Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Immunology, Tabriz Branch, Islamic Azad University, Tabriz, Iran.

Abstract

Purpose: Modafinil is a vigilance-enhancing drug licensed for narcolepsy. The use of modafinil leads to various neuromodulatory effects with very low abuse potential. A body of evidence suggested that modafinil may have anti-parkinsonian effects. This study was designed to evaluate whether modafinil could improve motor dysfunction in the 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson’s disease. Methods: Male Wistar rats (180-220 g, n= 98) were used in this study. Parkinsonism was induced by injection of 6-hydroxydopamine (10 μg/2μl in 0.2 % ascorbic acid-saline) into the right striatum. Parkinsonian rats received intraperitoneal (ip) injections of modafinil (50, 75, and 100 mg/kg) and catalepsy-like immobility was assessed by the bar test (BT). Furthermore, involvement of dopamine D1 and D2 receptors in modafinil’s anti-parkinsonian effects was studied. For this purpose, parkinsonian animals were pretreated with SCH23390 and raclopride (the dopamine D1 and D2 receptor anatgonists, respectively) or SCH23390 + raclopride, and then assessed by the BT. Results: Modafinil (100 mg/kg) showed anti-cataleptic effects in the BT. Notably, the effect of modafinil in the BT was reversed in parkinsonian rats pretreated with raclopride (1.25 mg/kg) and/or SCH23390 + raclopride (0.75 and 1.25 mg/kg, respectively), but not in those pretreated with SCH23390 (0.75 mg/kg). Conclusion: Acute administration of modafinil improves 6-OHDA-induced motor impairment possibly through activation of dopamine D2 receptors.
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Submitted: 21 Nov 2016
Revised: 13 Jul 2017
Accepted: 16 Jul 2017
First published online: 25 Sep 2017
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