Hyperactivity, memory deficit and anxiety-related behaviors in mice lacking the p85α subunit of phosphoinositide-3 kinase

We previously reported that knockout mice lacking the p85α regulatory subunit of phosphoinositide-3 kinase (PI3K) (p85α^-/- mice) significantly showed spatial learning-deficits, restlessness and motivation-deficit in water maze tests. It was also shown in the report that decline of PI3K activity in several brain areas related to losses of synapses and myelinated axons. However, any other behavioral patterns have not been elucidated, the aim of the present study was to observe behavioral natures of in p85α^-/- mice using several behavioral tests. In order to examine behaviors, a novel object recognition test, an open field test, an object exploring test, a hole-board test and an elevated plus maze test were carried out in p85α^-/- mice. The p85α^-/- mice significantly showed a deficit in object recognition memory, less exploring novel objects, and anxiety. Hyperactivity was observed in p85α^-/- mice in male-specific manner. The present results suggest that deficiencies in PI3K activity result in hyperactivity, memory deficit and an increase in anxiety. Therefore, these behavioral phenotypes can be analyzed in a relationship with losses of synapses and myelinated axons in the brain, which resulted from deficiencies in PI3K activity.