Effect of thiamine deficiency on brain serotonin turnover

Serotonin turnover has been investigated in regional brain areas of rats made thiamine deficient by pyrithiamine (PT). Following intracisternal injection of [¹⁴C]5-hydroxytryptamine ([¹⁴C]5-HT), a marked increase in the accumulation of [¹⁴C]5-hydroxyindoleacetic acid ([¹⁴C]5-HIAA) was found in the medulla-pons, hypothalamus and cerebral cortex. [¹⁴C]5-HT levels were normal in all of the brain areas except the cerebral cortex which had an increase of 58%. The ratio of [¹⁴C]5-HIAA/[¹⁴C]5-HT was significantly increased in every brain region of PT-treated rats except the cerebral cortex. Part of this increase in [¹⁴C]5-HIAA was shown to be due to impairment of active transport of this 5-HT metabolite out of the brain. However, increased 5-HT synthesis in the cerebellum, hypothalamus, striatum, hippocampus and cerebral cortex was demonstrated by measurement of 5-HT accumulation after inhibition of brain monoamine oxidase. PT-induced increase in endogenous 5-HIAA in the medulla-pons occurred simultaneously with the onset of neurological signs and both parameters were reversible by thiamine administration. These results suggest that acute thiamine deficiency, induced by PT, both increases brain 5-HT synthesis and impairs 5-HIAA efflux from the brain. There is a close correlation between neurological manifestations and changes in brain 5-HT metabolism in acute thiamine deficiency.