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A possible role for N-acetylserotonin (NAS) as a central nervous system neurotransmitter was investigated. Of the generally accepted criteria which are used to define transmitter function, those of localization and physiologic effect were pursued. Various immunohistochemical techniques were used to show the hippocampal distribution of NAS. This distribution was found to be distinctly different from that of melatonin and that reported for serotonin. NAS was located in sub-micron sized structures immediately adjacent to the hippocampal pyramidal cells in areas CA1 and CA3. There was also evidence for cells containing substantial quantities of NAS in the CA4/dentate region. Some fibres could also be identified here. The presence of NAS in the hippocampus of the rat was confirmed by gas chromatography-mass spectrometry (GCMS). Attempts to identify an extra-hippocampal source for the NAS found in hippocampus by use of lesions did not provide evidence that hippocampal NAS is dependent on an intact projection from brainstem via the fimbria-fornix pathway. A study using the 5HT synthesis blocker, p-chlorophenylalanine, showed that hippocampal NAS content can be reduced by this drug, as measured by GCMS. Immunohistology was further used to identify a population of cells which might be expected to respond to NAS, those being the pyramidal cells of the hippocampus. In the hippocampal slice preparation, NAS and 5HT were equally potent in inhibiting glutamate-induced cellular activity, as measured extracellularily. Melatonin could not affect the firing rate of the pyramidal cells. It is concluded that this line of research may be useful in further defining the functional role of NAS in the CNS of rat.

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