Hippocampal 5-HT_1A receptor binding is related to object–location memory in humans

Animal studies suggest that serotonin, mediated by the 5-HT_1A receptor, plays a key role in spatial learning and memory. The role of serotonin in spatial memory in humans has, however, been less well studied. This study examined the relationship between serotonin receptor density in the human brain and spatial learning and memory using the 5-HT_1A receptor ligand ¹⁸F-4-(2′-methoxyphenyl)-1-[2′-(N-2-pyridinyl)-p-fluorobenzamido]-ethyl-piperazine ([¹⁸F] MPPF) and positron emission tomography (PET). Ten neurologically healthy individuals underwent two [¹⁸F] MPPF PET scans, one while performing a task which involves processing of high-level spatial information (‘house scan’), and one while performing a task which involves processing of low-level spatial information (‘tunnel scan’). Navigation, recall of arbitrary associations between objects and their spatial location, and ability to draw a plan of the environment were tested following the house scan. 5-HT_1A receptor binding did not differ significantly between processing high and low levels of spatial information. Hippocampal asymmetry in [¹⁸F] MPPF binding, however, was associated with memory for object–location associations; lower right than left hippocampal binding potential (BP_ND) was related to better memory performance. We conclude that hippocampal serotonergic function plays a role in a fundamental component of human spatial memory, the ability to recall the location of encountered objects.