Effects of sub-chronic caffeine ingestion on memory and the hippocampal Akt, GSK-3β and ERK signaling in mice.

Caffeine, one of the most widely consumed psychoactive substance in the world, has been shown to affect mood, memory, alertness, and cognitive performance. This study aimed to assess the effect of sub-chronic oral gavage of caffeine on memory and the phosphorylation levels of hippocampal Akt (protein kinase B), GSK-3β (Glycogen Synthase Kinase-3beta) and ERK (extracellular signal-regulated kinase) in mice. Adult male NMRI mice were administered with caffeine at the doses of 0.25, 0.5, 0.75 and 1.5 mg/kg/oral gavage for 10 days before behavioral assessments. Upon completion of the behavioral tasks, the hippocampi were isolated for western blot analysis to detect the phosphorylated and total levels of Akt, GSK-3β and ERK proteins. The results showed that sub-chronic caffeine ingestion at the dose of 0.5 mg/kg improves memory in mice both in passive avoidance and novel object recognition tasks. Furthermore, this memory enhancing dose of caffeine elevated the ratios of phosphorylated to total contents of hippocampal Akt, GSK-3β and ERK. This study suggests that sub-chronic low dose of caffeine improves memory and increases the phosphorylation of hippocampal Akt, GSK-3β and ERK proteins.