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Chronic treatment with the glutamate receptor antagonist MK‐801 alters periodontal disease susceptibility
Author(s) -
Breivik Torbjørn,
Gundersen Yngvar,
Osmundsen Harald,
Opstad Per Kristian,
Fonnum Frode
Publication year - 2005
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2004.00765.x
Subject(s) - endocrinology , medicine , glutamate receptor , corticosterone , stimulation , nmda receptor , antiglucocorticoid , receptor antagonist , glucocorticoid receptor , hippocampus , glucocorticoid , receptor , lipopolysaccharide , tumor necrosis factor alpha , antagonist , hormone
Objective: Previous experiments in rats suggest that hypothalamic–pituitary–adrenal (HPA) axis over‐responsiveness, which leads to increased secretion of immunoregulatory glucocorticoid hormones, increases periodontal disease susceptibility, whereas HPA axis under‐responsiveness is associated with increased resistance to the disease. The present study was designed to investigate whether MK‐801 (dizocilipine malate), an antagonist of the glutamate receptor N ‐methyl‐ d ‐aspartate (NMDA) in the brain, which has been found to play an important role in the regulation of the HPA axis, would influence the outcome of experimental ligature‐induced periodontal disease in a rat model. Methods: Experimental periodontal disease was induced in periodontal disease susceptible and HPA axis high‐responding Fischer 344 rats 2 days before chronic treatment with MK‐801(1 mg/kg intraperitoneally). The periodontal breakdown was assessed after the ligatures had been in place for 23 days. Following intraperitoneal Gram‐negative bacterial lipopolysaccharide stimulation ( Escherichia coli , 250 µg/kg), concentrations of glucocorticoid receptors (GRs) in the hippocampus, and levels of the cytokine tumour necrosis factor α (TNF‐α), as well as the HPA axis‐derived hormone corticosterone, were measured in serum. Results: Compared to vehicle‐treated controls, MK‐801‐treated rats had significantly increased periodontal tissue destruction ( p < 0.01). MK‐801‐treated rats also showed significantly increased expression of GRs in the hippocampus ( p < 0.05), elevated levels of corticosterone ( p < 0.001) and reduced levels of TNF‐α ( p < 0.01) in serum 2 h after lipopolysaccharide stimulation. Conclusion: These findings may implicate glutamate receptor‐dependent mechanisms in periodontal disease, and support the concept of a bidirectional immune–brain–immune regulatory network with importance for periodontal health and disease.