Dopamine agonist Rotigotine mitigates lipopolysaccharide-induced neuroinflammation and memory impairment in mice

Metab Brain Dis. 2024 Nov 20;40(1):23. doi: 10.1007/s11011-024-01463-z.

Abstract

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.

Keywords: Amyloid beta; Dopamine; Lipopolysaccharide; Memory impairment; Neuroinflammation; Rotigotine.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / metabolism
  • Dopamine Agonists* / pharmacology
  • Lipopolysaccharides*
  • Male
  • Memory Disorders* / chemically induced
  • Memory Disorders* / drug therapy
  • Memory Disorders* / metabolism
  • Mice
  • Neuroinflammatory Diseases* / drug therapy
  • Neuroinflammatory Diseases* / metabolism
  • Oxidative Stress / drug effects
  • Tetrahydronaphthalenes* / pharmacology
  • Tetrahydronaphthalenes* / therapeutic use
  • Thiophenes* / pharmacology
  • Thiophenes* / therapeutic use

Substances

  • rotigotine
  • Tetrahydronaphthalenes
  • Thiophenes
  • Lipopolysaccharides
  • Dopamine Agonists