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Published on: October 26, 2010
Dopamine agonist Rotigotine mitigates lipopolysaccharide-induced neuroinflammation and memory impairment in mice
Prasada Chowdari Gurram1,2, Sairaj Satarker1, Ajmal Nassar1
1Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Background:
Dopaminergic signaling in the Central Nervous System (CNS) has been observed in the pathophysiology of memory deficits. Rotigotine belongs to a non-ergot-based dopamine receptor agonist possessing anti-inflammatory properties. However, it is uncertain if it has a role in ameliorating cognitive decline. Here, we evaluated the actions of rotigotine on neuroinflammation and memory impairment.
Methodology:
Rotigotine 1, 3, and 5 mg/kg were administered to mice subcutaneously once a day for fifteen days. Lipopolysaccharide (LPS) 750 µg/kg was administered intraperitoneally for seven days to produce cognitive impairment in mice. Morris water maze and Passive avoidance step-down tests were performed to evaluate memory function. Further, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and amyloid-beta (Aβ) were estimated by ELISA. The mouse brain was analyzed for acetylcholinesterase (AChE) activity, lipid peroxidation, catalase, and reduced glutathione levels.
Results:
LPS elevated IL-6, Aβ, TNF-α, and AChE activity, promoted oxidative stress, and caused memory decline in mice. Lower doses of rotigotine 1 and 3 mg/kg significantly reduced neuroinflammation, oxidative stress, and AChE activity, followed by improved cognitive impairment.
Conclusion:
Our data suggest that rotigotine 1 and 3 mg/kg could reverse the neuroinflammation-associated memory impairment.
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