Dopaminergic agonist pramipexole improves memory and increases IL-10 production in LPS-challenged rats

Document Type : Original Article

Authors

1 Department of Pharmacology and Drug Toxicology, Faculty of Pharmacy, Medical University of Plovdiv, Bulgaria

2 Department of Pharmacology and Clinical Pharmacology, Medical Faculty, Medical University of Plovdiv, Bulgaria

3 Department of Microbiology and Immunology, Research Institute (RIMU), Faculty of Pharmacy, Medical University of Plovdiv, Bulgaria

4 Department of Anatomy, Histology and Embryology, Medical Faculty, Medical University of Plovdiv, Bulgaria

Abstract

Objective(s): A variety of cytokines are involved in cognitive functioning. Balance restoration between protective and degenerative neuro-inflammation is of great interest in newer therapeutic approaches. In the current study, we investigated the effect of pramipexole (PMX) on memory functions, hippocampal amyloid deposition, serum cytokines, and brain-derived neurotrophic factor (BDNF)  levels in lipopolysaccharide (LPS) challenged-rats.
Materials and Methods: Male Wistar rats were divided into 5 groups (n=8): control (saline), lipoppolysacharide (LPS 250 mcg/kg bw), and experimental groups (LPS and PMX 0.5, 1, and 3 mg/kg bw). Learning and memory were assessed by the novel object recognition test (NORT), Y-maze, and step-through test. Immunological and histological assays were performed.
Results: In memory tasks, LPS-challenged rats showed reduction in the observed parameters. In NORT, PMX 1 mg/kg increased recognition index compared with controls, whereas the other two doses increased this index only against the LPS-control. In Y-maze, all doses of PMX significantly had increased alternation when compared with LPS. In the step-through test, only the lowest dose of PMX extended the latency compared with LPS. Histological examination revealed that PMX at doses of 0.5 and 1 mg/kg reduced amyloid deposition in the hippocampus. Interleukin (IL)-10 serum levels were elevated by 1 mg/kg PMX. Tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 serum levels remained under the detectable minimum in all experimental groups. PMX at all doses significantly decreased BDNF serum concentration.
Conclusion: In rats with LPS-induced neuro-inflammation PMX improved hippocampal-dependent memory and exerted immuno-modulatory effects by increasing IL-10.

Keywords


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