Evidence for the existence of monoamine neurons in the central nervous system

Summary With the help of the highly specific and sensitive fluorescence method of Falck and Hillarp together with the histochemical and pharmacological criteria for the specificity of the fluorescence reaction convincing evidence has been obtained that the fine, varicose nerve fibres observed in a vast number of regions in the mammalian central nervous system (mouse, hamster, rat, guineapig, rabbit, cat), which exhibit a green or yellow fluorescence, contain primary catecholamines and 5-HT respectively. Strong support has been given for the view that CA fibres showing a rapid recovery after administration of -MMT contain DA, while those showing a slow recovery contain NA.There is little doubt that the monoamine-containing fibres in the brain represent the terminal ramifications of axons belonging to specific monoamine neurons and that they are true synaptic terminals. They seem to make their contacts via the varicosities which have extremely high concentrations of amines and in all probability represent the presynaptic structures, specialized for synthesis, storage and release of the amines. The central monoamine terminals thus have the same characteristic appearance as the adrenergic synaptic terminals in the peripheral nervous system.All the data strongly support the view that the specific central neurons giving rise to the terminals are monoaminergic, i.e. function by releasing their amines from the synaptic terminals. Consequently, DA, NA and 5-HT seem to be central neurotransmitters.Not only the median eminence but also the nuc. caudatus putamen, tuberculum olfactorium, nuc. accumbens and the small circumscribed areas medial to nuc. accumbens contain very fine (partly sublightmicroscopical) CA terminals. These areas react to treatment with reserpine, nialamide-dopa and -MMT in the same way and since the nuc. caudatus putamen and tuberculum olfactorium are known to have a high DA content it seems likely that abundant DA terminals are accumulated in these special areas.The Following Abbreviations are Used CA Catecholamine - DA Dopamine - dopa 3.4-Dihydroxy-phenylalanin - NA Noradrenaline - A Adrenaline - 5-HT 5-Hydroxytryptamine - -MMT -Methyl-meta-tyrosine - MAO Monoamine oxidaseFor generous supplies of drugs the author is indebted to the following companies: Swedish Ciba, Stockholm, Sweden (reserpine); Swedish Pfizer, Stockholm, Sweden (nialamide); Abbott Research Laboratories, Chicago, USA. (MO 911). This study has been supported by a Public Health Service Grant (NB 02854-04) from the National Institute of Neurological Diseases and Blindness and by grants from the Knut and Alice Wallenberg Foundation, and the Swedish Medical Research Council.