EFFECT OF ACUTE CREATINE ADMINISTRATION ON NEUROCHEMICAL AND BEHAVIORAL DEFICITS IN A MODEL OF BIPOLAR DISORDER

Bipolar Disorder (BD) is a condition from the central nervous system characterized by mood changes that varies from constant depression states to mania and euthymic episodes and affects 1% of the world population. Recent research shows a relationship between BD symptoms and the reduction of Na+,K+-ATPase activity as well as an increase in glycogen synthase kinase 3 beta (GSK-3β) activity, which are associated with behavioral changes. Moreover, patients also show reduced creatine kinase (CK) activity and phosphocreatine (PCr) levels, both related to the maintenance of energetic homeostasis. In this sense, creatine supplementation has a great therapeutic potential in BD treatment, since it has been shown that creatine treatment may increase Na+,K+-ATPase activity, CK activity and AKT/mTOR pathway. Ouabain (OUA) is a potent inhibitor of Na+,K+-ATPase able to mimic behavior and biomarkers of mania in rats.