The serotonin (5-hydroxytryptamine, 5-HT) hypothesis postulates a causal relationship between mental depression and a 5-tIT deficiency in the brain. The data on which this hypothesis is based largely originate : a) from the periphery, and b)from post-mortem brain studies following suicide (surveys in Coppen, 1967; Lapin and Oxcnbrug, 1969;van Praag, 1969van Praag, , 1970)). These data give little information on the cerebral turnover of 5-HT. It is evident that a conclusive opinion on the 5-HT hypothesis must wait for suitable methods of obtaining information on the turnover rate of cerebral 5-HT in man. For this purpose, our group has recently used the so-called probenecid test in the study of depressions (van Praag et al., 1970a). Probenccid 1 is a compound which inhibits the passage of 5-hydroxyindolcacetic acid (5-HIAA, the principal metabolite of 5-HT) from brain and CSF to the blood circulation. Neff et al. (1967) have demonstrated that the rate of accumulation of 5-HIAA in the rat brain under the influence of probenecid, is a reliable measure of the turnover rate of cerebral 5-HT. In dogs given probenecid, the concentration of 5-HIAA in the CSF also increases (Gnldberg et al., 1966). There are indications (only indirect so far) that CSF acid amine metabolites are derived from brain amines, and that changes in CSF acid concentrations may reflect the metabolism of the parent cerebral amine (Bowers and * This study was supported by grants from the Netherlands Organization for Pure Research (Z.W.O.).
1 Probenecid is the generic name for p-(di-n-propylsulfamyl)-benzoic acid, which is marketed under the trademark "Benemid" by Merck Sharp and Dohme, Inc. Thanks go to the manufacturers for generous supplies of probenecid for intravenous use.