The effect of prolonged lithium treatment on the synthesis rate and turnover of monoamines in brain regions of rats

A. K.S. Ho, H. H. Loh, F. Craves, R. J. Hitzemann, S. Gershon

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The effect of prolonged lithium treatment on the dteady state levels and turnover rates of serotonin (5-HT), norepinephrine and dopamine was studied in the cerebral cortex, cerebellum, diencephalon, brain stem and hypothalamus. In normal rats, all 3 monoamines showed significant differences in the steady state levels and turnover rates among brain regions. The highest and lowest rates of synthesis of both 5-HT and norepinephrine were found in the hypothalamus and cerebellum respectively, while the rate of synthesis of dopamine was highest in the diencephalon and lowest in the cerebellum. Prolonged lithium treatment produced a significant change on 5-HT levels only in the hypothalamus (46% reduction) and brain stem (26% reduction) but no significant change in the other regions. There was no significant alteration in both norepinephrine and dopamine levels in any of the 5 discrete areas studied. The turnover rate of 5-HT was slight but not significantly changed by lithium in whole brain studies. However, a significant effect was observed in regional studies. The cerebellum showed a 37% increase in the synthesis rate whereas the hypothalamus showed a 51.1% reduction. The turnover rates of both norepinephrine and dopamine were not significantly affected in most brain regions by prolonged lithium treatment. The mean concentration of lithium in the serum and whole brain were 1.96 meq/l and 0.88 meq/kg respectively. These findings suggest that there may be a variable relationship between the tissue concentration and synthesis rates of the monoamines under both normal conditions and lithium treatment. It was concluded that the observed differences in the action of lithium on monoamines in the regions studied may be related to the morphology of these discrete areas.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number1
StatePublished - Apr 1970
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by USPHS grants MH-12383, MH-17916-01, and MH-08638. Dr. Ho is the recipient of a PMA Foundation award in morphological pharmacology.


  • Dopamine
  • Effect of chronic lithium Serotonin
  • Norepinephrine
  • Turnover rates in brain areas


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