Electrochemical monitoring of 5-hydroxytryptamine release in vitro and related in vivo measurements of indoleamines.

1. Electrochemical techniques have been used to measure release of endogenous 5HT from brain regions in vitro and to record electrochemical changes induced by drugs acting on 5HT neurones in the anaesthetised and unanaesthetised rat in vivo. 2. 5HT release in vitro was observed in all regions studied. The highest level of basal release was observed in the nucleus accumbens/septal region and hypothalamus and the lowest in the striatum. 3. High potassium (55 mM) increased release of 5HT in all regions, where their basal release was observed. 5HT release was also increased by p-chloroamphetamine (1-10 microM). 4. In rats anaesthetised with pentobarbitone, three electrochemical peaks were observed in the striatum, nucleus accumbens and frontal cortex at + 0.12 V, +0.2 V and + 0.35 V using a micro-graphite paste electrode and differential pulse voltammetry. 5. The peak at + 0.12 V was increased by micro-infusion of ascorbic acid (5 X 10(-6) M) and that at + 0.35 V by micro-infusion of 5HT (5 X 10(-6) M) and 5-hydroxyindole acetic acid (5HIAA) (5 X 10(-6) M). 6. p-Chlorophenylalanine (2 X 150 mg/kg) caused the loss of the peak at + 0.35 V. Fenfluramine (10 mg/kg) also decreased the peak at + 0.35 V. 7. The results indicate the validity of the in vitro technique and demonstrate the future potential of the in vivo method, though further studies are needed to determine the precise chemical nature of the changes in oxidation following administration of drugs acting on 5HT neurones.