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Because of the importance of stress in recruiting KORs it is not surprising that, in contrast to DOR KO mice, KOR KO mice did not differ from controls in classical behavioral models of depressive-like behaviors involving limited stress [16]

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Furthermore, epigenetic modifications, particularly DNA methylation [9], have been implicated in the development and progression of the disease, suggesting that these alterations may serve as potential therapeutic targets [10] For example, aberrant DNA methylation profiles have been associated with inflammation and neurodegeneration in MS patients, indicating a complex interplay between genetic and epigenetic factors [6,11]