The 5-HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans

The cerebral serotonin (5-HT) system is involved in cognitive functions such as memory and learning and animal studies have repeatedly shown that stimulation of the 5-HT type 4 receptor (5-HT4 R) facilitates memory and learning and further that the 5-HT4 R modulates cellular memory processes in hippocampus. However, any associations between memory functions and the expression of the 5-HT4 R in the human hippocampus have not been investigated. Using positron emission tomography with the tracer [(11) C]SB207145 and Reys Auditory Verbal Learning Test we aimed to examine the individual variation of the 5-HT4R binding in hippocampus in relation to memory acquisition and consolidation in healthy young volunteers. We found significant, negative associations between the immediate recall scores and left and right hippocampal BPND , (p = 0.009 and p = 0.010 respectively) and between the right hippocampal BPND and delayed recall (p = 0.014). These findings provide evidence that the 5-HT4 R is associated with memory functions in the human hippocampus and potentially pharmacological stimulation of the receptor may improve episodic memory.