For the last few decades, aggression has been linked to various modifications in cellular metabolic pathways. It has also been shown that patients undergoing extended creatine (Cr) treatment display increased aggressiveness. However, molecular mechanisms underlying a correlation between the two phenomena have not been sufficiently identified. To gain a deeper understanding of the changes resulting from supplementation of Cr into non-aggressive animals, we compared some behavioral and biochemical characteristics of Cr-treated and originally non-aggressive individuals with those of naturally non-aggressive and naturally aggressive groups. In this paper we show that extended supplementation of creatine into non-aggressive animals modifies the number of exploratory characteristics and fear-related reactions. In addition, it also changes several biochemical properties in the hippocampus among rats, by significantly reducing the content of Ca 2+ ions. This could be the result of Cr's direct influence on the NMDA-receptor and its functional inhibition. In conclusion, behavioral and biochemical parameters of non-aggressive individuals display changes under extended supplementation of creatine, which could provide a significant insight into formation of aggression-related behaviors and processes.
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