Therefore, the results observed in the current series of experiments clearly showed that H3R antagonism counteracted cognitive deficits by simultaneously modulating brain levels of HA and several other neurotransmitters by functioning as an H3R antagonist on H3 auto- and hetero-receptors, respectively, and by mitigating disturbances in hippocampal protein levels in the PI3K/AKT/GSK-3β signaling pathway following MK801-induced amnesia in mice. This evidence concerns the gene AKT1 and Cognitive impairment.