N-Acetylserotonin in the Central Nervous System

N-acetylserotonin has been identified by immunohistochemistry in specific brain areas separate from melatonin and serotonin. N-acetylserotonin is widely distributed within the brain stem, cerebellum and hippocampus and in the brain stem it is contained within the reticular formation nuclei and motor nuclei. Like serotonin, N-acetylserotonin appears to be derived from tryptophan as tryptophan hydroxylase inhibition leads to a lowering in immunoreactive N-acetylserotonin in brain and blood. Beta adrenergic drugs influence N-acetylserotonin neurons with beta adrenergic agonists causing a rise in immunoreactive N-acetylserotonin. The presence of N-acetylserotonin in brain has been confirmed by gas chromatography, mass spectrometry and radioimmunoassay. At this point little is known of the possible role of N-acetylserotonin in the brain. In the hippocampus N-acetylserotonin is present in granule cells and its appearance parallels the appearance of those cells. High affinity binding of tritiated N-acetylserotonin is found in brain and in various brain areas and this radioligand appears to label serotonergic receptors. Preliminary iontophoretic studies performed on hippocampal slices indicate an inhibitory action of N-acetylserotonin on glutamate induced firing of pyramidal cells. Taken together these findings suggest that N-acetylserotonin may have a role in the central nervous system distinct from that of being a precursor for melatonin. If this hypothesis is correct it would suggest that indoleamines have certain similarities to catecholamines. Thus for the catecholamines, dopamine, norepinephrine and epinephrine form a synthetic sequence and yet have independent roles as neurotransmitters and/or hormones. The three indoleamines serotonin, N-acetylserotonin and melatonin also form a synthetic sequence and these three substances may also have independent roles as neurotransmitters and/or hormones.