Fluoxetine Inhibits Natural Decay of Long-Term Memory via Akt/GSK-3β Signaling

초록

Understanding the mechanisms underlying the natural decay of long-term memory can help us find means of extending the duration of long-term memory. However, the neurobiological processes involved in the decay of long-term memory are poorly understood. In the present study, we examined the effect of acute and chronic treatment of fluoxetine on natural decay of long-term memory and the possible mechanism. Late administration of fluoxetine prolonged the persistence of long-term memory in mice, as demonstrated by object location recognition and Barnes maze tests. Fluoxetine altered Akt/glycogen synthase kinase-3 beta (GSK-3 beta)/beta-catenin signaling in the hippocampus. Late short- and long-term pharmacological inhibition of GSK-3 beta mimicked the effect of fluoxetine on memory persistence. Pharmacological inhibition of Alct blocked the effect of fluoxetine on memory persistence. Finally, late infusion of fluoxetine increased hippocampal long-term potentiation (LTP) and pharmacological inhibition of GSK-3 beta blocked the natural decline in LTP. These results demonstrate that GSK-3 beta might be a key molecule in memory decay process, and fluoxetine extends the period of long-term memory maintenance via Alct/GSK-3 beta signaling.

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