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Effects of Lithium and of pH on Synaptosomal Metabolism of Noradrenaline

Abstract

CURRENT hypotheses about mania and depression are that they correspond to greater or lesser availability of catecholamines at central synapses1, or to changes in electrolyte and water distribution2. The mode of action of lithium salts, which seem to be effective at least in mania, has been related to both hypotheses3. There are several findings regarding catecholamine metabolism. They include a disappearance of brain noradrenaline after inhibition of tyrosine hydroxylase which is more rapid following Li+ treatment4; a shift in brain metabolism of noradrenaline from extracellular methylation (by catechol-O-methyl transferase), toward intraneuronal deamination (by monoamine oxidase)5; and a decreased rate of release of 3H-noradrenaline during electrical stimulation of brain slices in vitro6. Evidence regarding effects of Li+ on active uptake of noradrenaline into neurones, a major means of inactivation of catecholamine released at synapses, is somewhat in conflict. One study7 reported enhanced uptake in vitro of 3H-noradrenaline into synaptosomes (“pinched-off nerve endings”) prepared after the administration of large amounts of unneutralized Li2CO3. This finding has not been confirmed, and there is evidence that uptake of 3H-noradrenaline into intact brain5, or brain slices6, may not be altered by prior treatment of rats with LiCl. Thus questions arise as to the effect of carbonate ion or pH on amine uptake. These findings, together, suggest that lithium may tend to keep noradrenaline in a pre-synaptic location, while increasing catabolism, particularly by oxidative deamination. The net effect would be decreased availability of this putative transmitter at central synapses, an interpretation consistent with the antimanic effects of lithium.

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BALDESSARINI, R., YORKE, C. Effects of Lithium and of pH on Synaptosomal Metabolism of Noradrenaline. Nature 228, 1301–1303 (1970). https://doi.org/10.1038/2281301a0

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