M. B. Bowers
Jun 1, 1970
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Journal
Journal of Neurochemistry
Abstract
VALUES for levels in CSF of 5-hydroxyindoleacetic acid (SHIAA), the acidic metabolite of 5-hydroxytryptamine (5 HT), have been reported for a number of clinical conditions. The assumption underlying such studies is that 5HIAA in the CSF bears some reliable relationship to 5HIAA in the central nervous system and thus may be used to study natural or drug-induced alterations in central metabolism of 5-HT in man. There is presently only limited evidence to support this assumption since 5HIAA in CSF and brain has rarely been measured simultaneously and compared in a single experimental animal. Accordingly, we have measured SHIAA in the CSF and whole brains of rabbits following the administration of a variety of compounds known to &ect 5-HT metabolism. Male New Zealand white rabbits (2-3 kg) were killed at varying times after injection of one of the following: probenecid (200 mglkg body wt. intraperitoneally), L-tryptophan (800 mg/kg intrapetitoneally), iproniazid (100 mg/kg intraperitoneally), reserpine ( 5 mg/kg intraperitoneally), or DLparachlorophenylalanine (PCPA, 200 mg/kg intraperitoneally , two injections). Cisternal samples of CSF (1.0 ml) were obtained under ether anaesthesia prior to killing by cervical dislocation and were frozen until assayed (GERBODE and BOWERS, 1968). This method measures total 5-hydroxyindoles in CSF which we have assumed is primarily 5HIAA (ASHCROFT, CRAWFORD, ECCLESTON, SHARMAN, MACDOUGALL, STANTON and BINNS, 1966). The whole brain (minus cerebellum) was removed, and the right hemisphere was frozen until assayed for 5HIAA (SHEARD and AGHAJANIAN, 1968). Control samples of brain and CSF were similarly obtained from untreated animals. Ratios between CSF and brain 5HIAA were calculated for the various experimental conditions. Following injection of probenecid, 5HIAA in brain and CSF rose linearly for at least 1 hr, the rate of increase being greater for brain. The rate of 5-HT synthesis under these conditions was 0.23 pg/g wet wt. of brain/hr, calculated on the basis of 5HIAA accumulation (NEFF, TOZER and BRODJE, 1967). This value is lower than that reported by NEFF et al. (1967) for rats. The rate of rise of SHIAA in CSF (0.14 ,ug/ml/hr) was greater than we observed for the cat under pentobarbital anaesthesia (BOWERS and GERBODE, 1968).