Inhibitory effect of hippocampal 5-HT1A 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.


METHODS
Using positron emission tomography (PET) with [(11)C]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.
Yasuno
Fumihiko
F
Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan.
Suhara
Tetsuya
T
Nakayama
Takashi
T
Ichimiya
Tetsuya
T
Okubo
Yoshiro
Y
Takano
Akihiro
A
Ando
Tomomichi
T
Inoue
Makoto
M
Maeda
Jun
J
Suzuki
Kazutoshi
K
D000328:Adult; D001288:Attention / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D054833:Isoindoles; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D010919:Placebos; D011725:Pyridines; D011743:Pyrimidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014055:Tomography, Emission-Computed; D014706:Verbal Learning / Q000187:drug effects / Q000502:physiology; D014888:Wechsler Scales
D054833:Isoindoles; D010879:Piperazines; D010919:Placebos; D011725:Pyridines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C055267:tandospirone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide