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.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative condition characterizing with motor symptoms including akinesia, bradykinesia, tremor at rest, rigidity[1] and leads to extensive biochemical and molecular alterations in cerebral structures that are involved in motor function.[2,3] Dopamine (DA) regulates normal motor activity through D1 and D2 receptors that are found postsynaptically on the dopaminergic (DAergic) neurons[4] in the striatum.[5]
Post hoc analysis showed that 6OHDA (10 μg/ rat) increased catalepsy time in the bar test (BT), which indicates that this neurotoxin is able to produce marked catalepsy
Effect of modafinil on the BT One-way ANOVA showed that modafinil could attenuate catalepsy time in 6-OHDA-lesioned rats [F(3,28) = 375.27 p
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative condition characterizing with motor symptoms including akinesia, bradykinesia, tremor at rest, rigidity[1] and leads to extensive biochemical and molecular alterations in cerebral structures that are involved in motor function.[2,3] Dopamine (DA) regulates normal motor activity through D1 and D2 receptors that are found postsynaptically on the dopaminergic (DAergic) neurons[4] in the striatum.[5]. Development of effective therapies to manage PD complications is of great interest
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