Monitoring the Effect of a Tryptophan Load on Brain Indole Metabolism in Freely Moving Rats by Simultaneous Cerebrospinal Fluid Sampling and Brain Dialysis

Abstract

Rats were given L-tryptophan, 50 mg/kg i.p., and its concentration in the CNS was monitored in individual freely moving animals using repeated sampling of cisternal CSF and concurrent striatal dialysis. The 5-hydroxytryptamine metabolite 5-hydroxyindoleacetic acid (5-HIAA) was also measured. Results were compared with changes of central tryptophan and 5-HIAA concentrations in brains of rats killed at various times after administration of L-tryptophan, 50 mg/kg i.p. Tryptophan changes in CSF were proportionate to those in whole brain and followed essentially identical time courses. Results for the striatal dialysate and whole striatum also paralleled each other. Similarly, results for 5-HIAA showed proportionality between CSF and brain and between dialysate and striatum. The data obtained were used to determine pharmacokinetic data for individual rats, i.e., areas under curves for both tryptophan and 5-HIAA and half-lives for the decline of tryptophan. Kinetic parameters varied considerably from rat to rat. However, mean half-lives for tryptophan in CSF, brain, dialysate, and striatum were all comparable. Results in general show the value of repeated CSF sampling and intracerebral dialysis for concurrent monitoring of changes of indole metabolism in the whole brain and a specific brain region, respectively. The methods should be suitable for the continuous monitoring of changes of central transmitter metabolism in parallel with observation of behavior following environmental or dietary changes or drug administration. They also should be of use in the investigation of drug kinetics in the CNS.

NMDA‐induced glutamate and aspartate release from rat cortical pyramidal neurones: evidence for modulation by a 5‐HT1A antagonist

“…The microdialysis probe used was based on those described previously (Hutson et al, 1985) To determine dead volume and in vitro recovery probes were placed in 40 ml mPBS containing glutamate and aspartate (50 gM) at 370C. Nine (collection time: 10 min) samples were collected and analysed for glutamate and aspartate concentration using h.p.l.c.…”

Efflux of glutamate produced by short ischemia of varied severity in rat striatum.

“…Microdialysis concentric cannulas 22 incorporated a small chlorided silver wire to enable monitoring of EEG and DC potential exactly at the same location (T.P. Obrenovitch and G.S.…”

Changes in extracellular glutamate concentration produced in the rat striatum by repeated ischemia.

“…Both vertebral arteries were cauterized at the level of the first cervical vertebra. 12 -13 Concentric microdialysis probes were constructed essentially as described by Hutson et al 14 but were modified to permit EEG and DC potential recording within the same tissue site. 11 The probes were implanted in the dorsolateral striatum (coordinates: 0.8 mm posterior to the bregma, 4 mm lateral, and 7.5 mm deep from the dural surface).…”