Caffeine suppresses exercise-enhanced long-term and location memory in middle-aged rats: Involvement of hippocampal Akt and CREB signaling

•Caffeine impaired long-term and spatial memory ameliorated by exercise in aged rats.•The effects in memory are related to a decrease in hippocampal p-CREB signaling.•The effects on memory were not accompanied by alterations in the levels of Akt. The cognitive function decline is closely related with brain changes generated by age. The ability of caffeine and exercise to prevent memory impairment has been reported in animal models and humans. The purpose of the present study was to investigate whether swimming exercise and caffeine administration enhance memory in middle-aged Wistar rats. Male Wistar rats (18months) received caffeine at a dose of 30mg/kg, 5days per week by a period of 4weeks. Animals were subjected to swimming training with a workload (3% of body weight, 20min per day for 4weeks). After 4weeks, the object recognition test (ORT) and the object location test (OLT) were performed. The results of this study demonstrated that caffeine suppressed exercise-enhanced long-term (ORT) and spatial (OLT) memory in middle-aged and this effect may be related to a decrease in hippocampal p-CREB signaling. This study also provided evidence that the effects of this protocol on memory were not accompanied by alterations in the levels of activated Akt. The [3H] glutamate uptake was reduced in hippocampus of rats administered with caffeine and submitted to swimming protocol.