Octanoic Acid Produces Accumulation of Monoamine Acidic Metabolites in the Brain: Interaction with Organic Anion Transport at the Choroid Plexus

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Abstract
Effects of octanoic acid on monoamines and their acidic metabolites in the rat brain were analyzed by HPLC. Octanoic acid (1,000 mg/kg i.p.) elevated homovanillic acid levels by 54% in the caudate and 338% in the hypothalamus but increased 5‐hydroxyindoleacetic acid (5‐HIAA) levels in both the caudate and the hypothalamus by ∼ 50% compared with the control. A lower dose of octanoic acid (500 mg/kg) increased 5‐HIAA levels by 29% in the caudate and 20% in the hypothalamus. However, it did not produce any changes in the concentration of homovanillic acid in either the caudate or the hypothalamus. Treatment with octanoic acid also failed to change the level of dopamine, serotonin, and 3,4‐dihydroxyphenylacetic acid in the caudate and the hypothalamus. The role of carrier‐mediated transport in the clearance of 5‐HIAA from the rabbit CSF was also evaluated in vivo by ventriculocisternal perfusion. Steady‐state clearance of 5‐HIAA from CSF exceeded that of inulin and was reduced in the presence of octanoic acid. Because this transport system in the choroid plexus is normally responsible for the excretion of the serotonin metabolite from the brain to the plasma, accumulation of endogenously produced organic acids in the brain, secondary to reduced clearance by the choroid plexus, could be a contributing factor in the development of en‐cephalopathy in children with medium‐chain acyl‐CoA de‐hydrogenase deficiency who have elevated levels of octanoic acid systemically.

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