Previous strength training attenuates ouabain-induced bipolar disorder-related behaviors and memory deficits in rats: Involvement of hippocampal ERK/CREB and PI3K/AKT/mTOR pathways.

Bipolar disorder (BD) is a central nervous system condition that is typified by fluctuations in mood, oscillating between depressive and manic, and/or hypomanic episodes. The objective of this study was to test the hypothesis that strength training may act as a potent protector against behavioral and neurochemical changes induced by BD. A strength training protocol was performed with adult male Wistar rats, and seven days following the conclusion of training, a single ouabain injection was administered. Following ouabain administration, the animals were subjected to behavioral tests after the seventh (manic period) and fourteenth (depressive period) days. Subsequently, rats were euthanized and the hippocampus was collected for western blotting assays. We demonstrated that strength training provided protection against ouabain-induced behavioral changes, both during the manic and depressive periods, including increased locomotor activity, risk-taking and aggressive-like behaviors, and impaired memory performance. Furthermore, physical training protected against ouabain-induced decrease of neurogenesis/neuroplasticity-related pathways, including BDNF/TrKB/ERK/CREB and PI3K/AKT/mTOR/p70S6K. These findings suggest that strength training has a protective effect, attenuating or preventing BD-induced deficits, and may have therapeutic potential as an adjuvant treatment for this patient population in the future.