Inhibitory Effect of Hippocampal 5-HT_1A Receptors on Human Explicit Memory

OBJECTIVE: Recent studies have indicated that the serotonergic (5-HT) system plays important roles in memory function. However, the specific relationship between 5-HT_1A receptors and memory function is not clear in the human brain. To clarify this relationship, the authors determined the availability of 5-HT_1A receptors in the human brain and the relationship between regional receptor binding and memory function. METHOD: Using positron emission tomography (PET) with [¹¹C]WAY-100635, the authors examined 5-HT_1A receptors and assessed their relationship with memory function. The 5-HT_1A agonist tandospirone was then administered to investigate the effect of 5-HT_1A receptor stimulation on cognitive function and neuroendocrinological response. RESULTS: There was a significant negative correlation between explicit memory function and 5-HT_1A receptor binding localized in the bilateral hippocampus where the postsynaptic 5-HT_1A receptors are enriched. Furthermore, the administration of tandospirone dose-dependently impaired explicit verbal memory, while other cognitive functions showed no significant changes. The change in memory function paralleled those of body temperature and secretion of growth hormone, which were reported to be induced by the stimulation of postsynaptic 5-HT_1A receptors. CONCLUSIONS: Postsynaptic 5-HT_1A receptors localized in the hippocampal formation have a negative influence on explicit memory function, which raises the possibility that the antagonistic effect of postsynaptic 5-HT_1A receptors in the hippocampus leads to improvement of human memory function. Drugs that work as antagonists on postsynaptic 5-HT_1A receptors may be favorable for improved control of memory impairment.