—Using either tryptophan or 5‐hydroxytryptophan as the precursor, and examining the metabolites in whole rat brain and in brain regions of dog, the pattern of metabolites resembled that found under physiological conditions only after tryptophan administration. From these and other observations on the cerebral 5‐hydroxyindoles the main conclusions are firstly, that there are regional differences within brain in storage, turnover or metabolic fate of 5‐HT. Secondly, that the normal pathway appears to be well localized biochemically with linking of its succeeding steps, and thirdly, that turnover through the system is normally controlled by intracerebral tryptophan 5‐hydroxylase in both rats and dogs although there are differences between the species in the cerebral metabolism of 5‐HT.

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SUMMARY1. An operation on dogs for the implantation ofguide tubes to the lateral ventricle and cisterna magna and a method whereby the ventricular space can be repeatedly perfused in conscious and unrestrained animals are described.2. The characteristics of a recirculatory perfusion system were examined and the bulk formation and absorption of cerebrospinal fluid and the volume of the ventricular space perfused were derived from the concentrations achieved during the infusion of inulin into the system. 3. 5-hydroxyindol-3-ylacetic acid (5-HIAA), the acid metabolite of 5-hydroxytryptamine, and 3-methoxy-4-hydroxyphenylacetic acid (HVA), the main acid metabolite of dopamine, were demonstrated to be mainly removed from cerebrospinal fluid (c.s.f.) by an active transport system localized in the region of the fourth ventricle. 4. It was possible to inhibit the active transport of these acids from cerebrospinal fluid by pre-treating the dogs with probenecid.

Abstract— —Normal values for the concentration of 5‐HT, 5‐HIAA and tryptophan are established in various regions of the dog brain. After administration of tryptophan by intravenous injection the rise and fall of 5‐HT and 5‐HIAA were estimated at 1, 2 and 4 hr. Best fit quadratic regression curves obtained by computer programme were fitted to the data. Similar tryptophan doses were given to dogs and the 5‐HIAA concentration estimated in the cisternal CSF. Quadratic regression curves fitted to these values show that the concentration of 5‐HIAA in CSF reflects the changes of 5‐HIAA in the brain and in particular in the brain stem. a‐Methyl dopa pretreatment blocked the rise of 5‐hydroxyindoles in brain and CSF and appeared to inhibit tryptophan hydroxylase as well as decarboxylase.