The effect of ammonia infusion on brain monoamine metabolism in portacaval-shunted rats

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Abstract
The effect of ammonia infusion on monoamine metabolism was studied in the rat brain. Seven days after portacaval shunt (PCS) or sham operation animals were infused with ammonia or saline. Brain metabolism of serotonin and norepinephrine was studied after injection of a decarboxylase inhibitor (m-hydroxybenzylhydrazine, NSD 1015) which blocks the conversion of 5-hydroxytryptophan to serotonin and dihydroxyphenylalanine to dopamine. Neurologic testing was conducted before killing. Plasma and brain amino acids were measured. PCS animals infused with ammonia were in deep coma after 6 h infusion, whereas sham-operated animals were virtually unaffected. Brain amino acid analyses demonstrated increased concentrations of the aromatic amino acids and a tenfold increase in glutamine. Serotonin metabolism was diminished after 6 h. Dopamine synthesis was normal, but norepinephrine levels were low after 6 h. The study suggests that hyperammonemia in PCS rats results in a depression of the serotonin synthesis rate in accordance with two previous studies but in contrast to previous hypotheses on the regulation of serotonin metabolism.